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ADHD underappreciated in older adults
Negative consequences can develop from not treating ADHD, including job loss, suppressed income levels, low educational attainment, and difficulty maintaining relationships. Perhaps as many as 5% of adults have ADHD, which is highly hereditary.
Primary care physicians or family medicine clinicians are often best placed to diagnose ADHD in older adults, according to experts interviewed for this article. But first these providers need to tease out whether a patient has ADHD or another condition that is causing difficulties for these older adults.
However, clinicians may have a hard time discerning the symptoms of ADHD from that of other conditions of aging, such as mild cognitive impairment. Literature is lacking on best practices for screening and treating the condition in this population, according to a recent review published in the Expert Review of Neurotherapeutics, and a 2020 study by the same authors, epidemiologists, and psychiatrists based in Europe.
“If you don’t manage it, who will? It can be very hard to get psychiatric consults, almost impossible in some cases,” said Brendan Montano, MD, an internist in Cromwell, Conn., who specializes in treating ADHD.
A critical role for primary care and family medicine
Although no formal U.S. guidelines exist on diagnosis of adult ADHD, Dr. Montano stressed that adults usually present with symptoms such as chronic forgetfulness, distractibility, or procrastination. Hyperactivity is more internalized as a feeling of internal restlessness in this age group, Dr. Montano said, rather than the more visible hyper behavior seen in children.
“The two big ways that people present are thinking they have it or [being] in chaos of some sort,” perhaps because they have been fired or their spouse has asked for a divorce, Dr. Montano explained.
To assess the possibility of ADHD, a clinician could give a patient a six-item screening test that asks questions such as how often over the previous 6 months have they had trouble completing assignments or remembering appointments. If they report difficulty in four or more of the six areas in the brief screener, clinicians can move on to a longer 18-item screening tool developed by the World Health Organization, Dr. Montano said.
To make an ADHD diagnosis definitively, however, a patient needs to report sustained difficulties in at least two aspects of life: work, home, or social situations. And they have to indicate to a clinician that these troubles began before age 12.
“You have to really sit down and paint the picture with the patient: There are no shortcuts here,” said Lenard Adler, MD, a psychiatrist who directs the Adult ADHD program at New York University. Dr. Adler helped develop the six-item screener and is currently on a committee developing formal screening guidelines for adult ADHD in the United States.
He said that often, “ADHD cotravels with other mental health disorders like depression, bipolar disorders, anxiety disorders, and substance use disorders at least half the time.”
To tease out if a patient really has ADHD, clinicians can start with a more general screening for anxiety and hone in on the possibility of the condition if the anxiety screening reveals challenges with distractibility and forgetfulness, according to Karen Smith, MD, a family physician in Raeford, N.C.
“We can’t expect patients to walk through the door with the diagnosis stamped on their foreheads,” said Dr. Smith, who is a member of the board of directors for the American Academy of Family Physicians.
But a patient’s apparent signs of ADHD could be due to another condition such as hyperthyroidism or diabetes, Dr. Smith said. The driving principle is to take enough time to figure out exactly what is going on, she said, and then to treat accordingly. “If you ask the right questions, patients will give you good answers.”
Medications are often prescribed to help manage ADHD symptoms. These can include stimulants, controlled substances that include methylphenidate or amphetamine, or nonstimulants, such as atomoxetine and bupropion. Dr. Montano starts his patients on a lower dose and titrates them up rapidly until they reach the optimum dose that allows them to sustain focus and feel more productive. Patients complete frequent self-reports during this process.
“Any diversion is inappropriate,” said Dr. Montano, who writes a contract with his patients saying that stimulant medications will not be refilled if they are used more quickly than prescribed.
For older adults, physicians should make sure that stimulants do not exacerbate any underlying cardiovascular conditions, Dr. Montano said, and consult a cardiologist when needed.
The benefits of proper ADHD treatment can be profound, Dr. Adler noted, no matter when it begins.
“Older adults have lived their lives feeling they’ve been disorganized and a burden to their significant others, and only when they’ve taken medication have they really been able to organize their days and feel effective in their social interactions and with their families,” Dr. Adler said.
Dr. Montano has reported relationships with AbbVie, Axsome, Corium, Idorsia, Intracellular, Otsuka, Supernus, Sage/Biogen, Biohaven, Boehringer Ingelheim, Cassava, Eli Lilly, Intracellular, Janssen, Jazz, Sage, Supernus, Otsuka, and Tonix. Dr. Adler has reported relationships with Shire/Takeda Pharmaceuticals, National Football League, Major League Baseball, Corium, Otsuka, Neurocentria, Bracket/Signant, and SUNY; and is receiving royalty payments for developing adult ADHD assessments. Dr. Smith has reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Negative consequences can develop from not treating ADHD, including job loss, suppressed income levels, low educational attainment, and difficulty maintaining relationships. Perhaps as many as 5% of adults have ADHD, which is highly hereditary.
Primary care physicians or family medicine clinicians are often best placed to diagnose ADHD in older adults, according to experts interviewed for this article. But first these providers need to tease out whether a patient has ADHD or another condition that is causing difficulties for these older adults.
However, clinicians may have a hard time discerning the symptoms of ADHD from that of other conditions of aging, such as mild cognitive impairment. Literature is lacking on best practices for screening and treating the condition in this population, according to a recent review published in the Expert Review of Neurotherapeutics, and a 2020 study by the same authors, epidemiologists, and psychiatrists based in Europe.
“If you don’t manage it, who will? It can be very hard to get psychiatric consults, almost impossible in some cases,” said Brendan Montano, MD, an internist in Cromwell, Conn., who specializes in treating ADHD.
A critical role for primary care and family medicine
Although no formal U.S. guidelines exist on diagnosis of adult ADHD, Dr. Montano stressed that adults usually present with symptoms such as chronic forgetfulness, distractibility, or procrastination. Hyperactivity is more internalized as a feeling of internal restlessness in this age group, Dr. Montano said, rather than the more visible hyper behavior seen in children.
“The two big ways that people present are thinking they have it or [being] in chaos of some sort,” perhaps because they have been fired or their spouse has asked for a divorce, Dr. Montano explained.
To assess the possibility of ADHD, a clinician could give a patient a six-item screening test that asks questions such as how often over the previous 6 months have they had trouble completing assignments or remembering appointments. If they report difficulty in four or more of the six areas in the brief screener, clinicians can move on to a longer 18-item screening tool developed by the World Health Organization, Dr. Montano said.
To make an ADHD diagnosis definitively, however, a patient needs to report sustained difficulties in at least two aspects of life: work, home, or social situations. And they have to indicate to a clinician that these troubles began before age 12.
“You have to really sit down and paint the picture with the patient: There are no shortcuts here,” said Lenard Adler, MD, a psychiatrist who directs the Adult ADHD program at New York University. Dr. Adler helped develop the six-item screener and is currently on a committee developing formal screening guidelines for adult ADHD in the United States.
He said that often, “ADHD cotravels with other mental health disorders like depression, bipolar disorders, anxiety disorders, and substance use disorders at least half the time.”
To tease out if a patient really has ADHD, clinicians can start with a more general screening for anxiety and hone in on the possibility of the condition if the anxiety screening reveals challenges with distractibility and forgetfulness, according to Karen Smith, MD, a family physician in Raeford, N.C.
“We can’t expect patients to walk through the door with the diagnosis stamped on their foreheads,” said Dr. Smith, who is a member of the board of directors for the American Academy of Family Physicians.
But a patient’s apparent signs of ADHD could be due to another condition such as hyperthyroidism or diabetes, Dr. Smith said. The driving principle is to take enough time to figure out exactly what is going on, she said, and then to treat accordingly. “If you ask the right questions, patients will give you good answers.”
Medications are often prescribed to help manage ADHD symptoms. These can include stimulants, controlled substances that include methylphenidate or amphetamine, or nonstimulants, such as atomoxetine and bupropion. Dr. Montano starts his patients on a lower dose and titrates them up rapidly until they reach the optimum dose that allows them to sustain focus and feel more productive. Patients complete frequent self-reports during this process.
“Any diversion is inappropriate,” said Dr. Montano, who writes a contract with his patients saying that stimulant medications will not be refilled if they are used more quickly than prescribed.
For older adults, physicians should make sure that stimulants do not exacerbate any underlying cardiovascular conditions, Dr. Montano said, and consult a cardiologist when needed.
The benefits of proper ADHD treatment can be profound, Dr. Adler noted, no matter when it begins.
“Older adults have lived their lives feeling they’ve been disorganized and a burden to their significant others, and only when they’ve taken medication have they really been able to organize their days and feel effective in their social interactions and with their families,” Dr. Adler said.
Dr. Montano has reported relationships with AbbVie, Axsome, Corium, Idorsia, Intracellular, Otsuka, Supernus, Sage/Biogen, Biohaven, Boehringer Ingelheim, Cassava, Eli Lilly, Intracellular, Janssen, Jazz, Sage, Supernus, Otsuka, and Tonix. Dr. Adler has reported relationships with Shire/Takeda Pharmaceuticals, National Football League, Major League Baseball, Corium, Otsuka, Neurocentria, Bracket/Signant, and SUNY; and is receiving royalty payments for developing adult ADHD assessments. Dr. Smith has reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Negative consequences can develop from not treating ADHD, including job loss, suppressed income levels, low educational attainment, and difficulty maintaining relationships. Perhaps as many as 5% of adults have ADHD, which is highly hereditary.
Primary care physicians or family medicine clinicians are often best placed to diagnose ADHD in older adults, according to experts interviewed for this article. But first these providers need to tease out whether a patient has ADHD or another condition that is causing difficulties for these older adults.
However, clinicians may have a hard time discerning the symptoms of ADHD from that of other conditions of aging, such as mild cognitive impairment. Literature is lacking on best practices for screening and treating the condition in this population, according to a recent review published in the Expert Review of Neurotherapeutics, and a 2020 study by the same authors, epidemiologists, and psychiatrists based in Europe.
“If you don’t manage it, who will? It can be very hard to get psychiatric consults, almost impossible in some cases,” said Brendan Montano, MD, an internist in Cromwell, Conn., who specializes in treating ADHD.
A critical role for primary care and family medicine
Although no formal U.S. guidelines exist on diagnosis of adult ADHD, Dr. Montano stressed that adults usually present with symptoms such as chronic forgetfulness, distractibility, or procrastination. Hyperactivity is more internalized as a feeling of internal restlessness in this age group, Dr. Montano said, rather than the more visible hyper behavior seen in children.
“The two big ways that people present are thinking they have it or [being] in chaos of some sort,” perhaps because they have been fired or their spouse has asked for a divorce, Dr. Montano explained.
To assess the possibility of ADHD, a clinician could give a patient a six-item screening test that asks questions such as how often over the previous 6 months have they had trouble completing assignments or remembering appointments. If they report difficulty in four or more of the six areas in the brief screener, clinicians can move on to a longer 18-item screening tool developed by the World Health Organization, Dr. Montano said.
To make an ADHD diagnosis definitively, however, a patient needs to report sustained difficulties in at least two aspects of life: work, home, or social situations. And they have to indicate to a clinician that these troubles began before age 12.
“You have to really sit down and paint the picture with the patient: There are no shortcuts here,” said Lenard Adler, MD, a psychiatrist who directs the Adult ADHD program at New York University. Dr. Adler helped develop the six-item screener and is currently on a committee developing formal screening guidelines for adult ADHD in the United States.
He said that often, “ADHD cotravels with other mental health disorders like depression, bipolar disorders, anxiety disorders, and substance use disorders at least half the time.”
To tease out if a patient really has ADHD, clinicians can start with a more general screening for anxiety and hone in on the possibility of the condition if the anxiety screening reveals challenges with distractibility and forgetfulness, according to Karen Smith, MD, a family physician in Raeford, N.C.
“We can’t expect patients to walk through the door with the diagnosis stamped on their foreheads,” said Dr. Smith, who is a member of the board of directors for the American Academy of Family Physicians.
But a patient’s apparent signs of ADHD could be due to another condition such as hyperthyroidism or diabetes, Dr. Smith said. The driving principle is to take enough time to figure out exactly what is going on, she said, and then to treat accordingly. “If you ask the right questions, patients will give you good answers.”
Medications are often prescribed to help manage ADHD symptoms. These can include stimulants, controlled substances that include methylphenidate or amphetamine, or nonstimulants, such as atomoxetine and bupropion. Dr. Montano starts his patients on a lower dose and titrates them up rapidly until they reach the optimum dose that allows them to sustain focus and feel more productive. Patients complete frequent self-reports during this process.
“Any diversion is inappropriate,” said Dr. Montano, who writes a contract with his patients saying that stimulant medications will not be refilled if they are used more quickly than prescribed.
For older adults, physicians should make sure that stimulants do not exacerbate any underlying cardiovascular conditions, Dr. Montano said, and consult a cardiologist when needed.
The benefits of proper ADHD treatment can be profound, Dr. Adler noted, no matter when it begins.
“Older adults have lived their lives feeling they’ve been disorganized and a burden to their significant others, and only when they’ve taken medication have they really been able to organize their days and feel effective in their social interactions and with their families,” Dr. Adler said.
Dr. Montano has reported relationships with AbbVie, Axsome, Corium, Idorsia, Intracellular, Otsuka, Supernus, Sage/Biogen, Biohaven, Boehringer Ingelheim, Cassava, Eli Lilly, Intracellular, Janssen, Jazz, Sage, Supernus, Otsuka, and Tonix. Dr. Adler has reported relationships with Shire/Takeda Pharmaceuticals, National Football League, Major League Baseball, Corium, Otsuka, Neurocentria, Bracket/Signant, and SUNY; and is receiving royalty payments for developing adult ADHD assessments. Dr. Smith has reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
How targeted drugs can vanquish a virulent leukemia
“We went almost 3 decades with nothing, then all of a sudden we’ve had nine approvals in 5 or 6 years,” said Harvard Medical School, Boston, leukemia specialist Amir Fathi, MD, in an interview. “We’ve had a lot of advancement and a number of good options emerge.”
However, Dr. Fathi and other hematologists cautioned that the treatment landscape is becoming more complex to navigate. And they noted that prognoses for many older patients with AML remain grim. The expensive new treatments may only extend their lifespans by a matter of months, although some are surviving for years.
As the specialists explained, there are a variety of reasons why AML is especially difficult to treat.
“AML is one of the fastest growing human cancers, with tumor cell doubling times measured in mere hours in some patients. Therefore patients can present critically ill with white blood cell counts in the [hundreds of thousands of white blood cells per microliter instead of the normal range of 4,000-11,000]," said leukemia specialist Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y. “Because blood cells are found in every organ of the body, the sheer volume of rapidly growing cancer cells can overwhelm multiple organ systems in a very short amount of time. These rapid growing cells and the fact that the median age of diagnosis with AML is 67-70 years old makes this a clinically challenging cancer to treat. Chemotherapy strong enough to kill cancer cells run the risk of also harming the patient as well.”
Also, older patients often have comorbidities, and they face risks of infection from both the disease and its treatments, said AML specialist Nicole R. Grieselhuber, MD, PhD, of the Ohio State University, Columbus, in an interview.
Enter targeted therapy, which “has allowed individuals who previously were not candidates for cytotoxic chemotherapy because of their age or possible toxicities to receive effective therapy for AML,” Dr. Wang said. “Therapy directed at specific biological features of AML cells such as mutations (FLT3, IDH1, IDH2) or surface proteins (CD33) can augment the efficacy of conventional chemotherapy or in some cases (i.e., FLT3 inhibitors) be more effective than chemotherapy in controlling AML.”
Targeted therapy drugs “are expected to more selectively kill cancer cells and spare normal counterparts,” she added.
The FDA has approved nine targeted therapy drugs for AML in the last few years.
Retinoic acid and arsenic trioxide therapy for acute promyelocytic leukemia “has transformed this AML subtype into one of the most curable AML diseases,” Dr. Wang said. A 2017 long-term analysis of the drug combination found that complete remission was reached in 96% of 54 high-risk patients and 133 low-risk patients; the 5-year survival rate was 88%. (Some patients also received gemtuzumab ozogamicin, a CD33 antibody-drug conjugate.)
According to Dr. Wang, three FLT3 inhibitors have been approved for AML with the FLT3 mutation: midostaurin and quizartinib in the frontline setting in conjunction with intensive chemotherapy and gilteritinib for relapsed/refractory FLT3-mutant AML.
A 2017 study linked midostaurin plus chemotherapy to longer survival (hazard ratio for death = 0.78; P = .009), versus placebo plus chemotherapy, in patients aged 18-59. This year, a phase 3 randomized trial of quizartinib versus placebo linked the drug to longer survival median overall (31.9 months versus 15.1 months; P = .032) In a 2019 trial, patients who took gilteritinib had longer median overall survival (9.3 months versus 5.6 months; HR for death = 0.64; P < .001).
The success of these treatments “has led FLT3 mutant AML to be reclassified from a poor risk AML subtype to intermediate risk AML,” Dr. Wang said.
A 2022 report about FLT3 inhibitors cautioned, however, that “several drug resistance mechanisms have been identified” and added that “the benefit of FLT3 inhibitor maintenance therapy, either post chemotherapy or post transplant, remains controversial, although several studies are ongoing.”
Gemtuzumab ozogamicin is a monoclonal antibody connected to a chemotherapy drug, according to the American Cancer Society. “The addition of gemtuzumab ozogamicin to intensive chemotherapy has enhanced outcomes of favorable and intermediate risk disease,” Dr. Wang said.
Ivosidenib, olutasidenib, and enasidenib target the IDH1 or IDH2 genes in ADL. “These drugs seem to work by helping the leukemia cells mature (differentiate) into more normal cells,” according to the American Cancer Society. “Because of this, they are sometimes referred to as differentiation agents.”
In older adults, a combination treatment with venetoclax, a BCL-2 inhibitor, and a hypomethylating agent has become standard, Ohio State’s Dr. Grieselhuber said. The treatment is FDA approved.
There are caveats to targeted therapy in AML. The treatments can be enormously expensive, “and even patients with insurance are often shocked by the copay,” Dr. Grieselhuber said. It helps to work with pharmacists, social workers, or nurse navigators to help patients afford the treatments, she said.
Side effects vary by therapy and can include QT elongation and differentiation syndrome.
Most challenging of all, many AML patients still face shortened lifespans even if new treatments are available for them.
“Typically for older patients with AML, the lifespan of patients with therapy was 5-7 months and without therapy was 2-3 months,” Dr. Wang said. “Now, with regimens specifically designed for elderly and/or unfit subjects, many individuals are now routinely living more than a year: 14-18 months to 3-4 years.”
But “the vast majority of AML patients will still die of their disease with overall 5-year outcomes still less than 30% in all age categories,” she said. In addition, “fewer than 50% of AML patients are eligible for treatment with FDA-approved targeted therapies, as their disease biology does not express the mutation or protein needed for efficacy.”
Still, she said, “this represents a vast improvement.” And, she added, “in younger individuals, the combination of chemotherapy followed by allogeneic transplant has now permitted more of these individuals to be cured of their disease.” Dr. Grieselhuber noted that transplants are now considered appropriate even for patients in their 60s or early 70s, and they can be combined with targeted therapy.
Dr. Grieselhuber urged colleagues to keep in mind that quality-of-life preferences will play a role in some patient choices. For example, a elderly patient may reject burdensome infusion therapy and choose a pill instead, even if it has less efficacy. “There’s really no one-size-fits-all,” she said.
And, she added, it can be difficult to make choices about treatment because of the lack of randomized, head-to-head data regarding new therapies.
What’s on the horizon? Dr. Wang highlighted a novel class of targeted therapies called menin inhibitors for patients with NPM1-mutated AML, which she said accounts for one-third of patients with the disease. A treatment targeting disease in the 5%-10% patients with the KMT2A gene is also in the works, she said.
For now, Dr. Wang said it’s essential for clinicians “to perform timely comprehensive molecular and genomic tests on all AML patients at diagnosis and relapse to determine which individuals would benefit from targeted therapy versus cytotoxic chemotherapy. And participation in clinical trials at every stage of AML therapy can help accelerate clinical development of new agents for this disease.”
Dr. Fathi discloses relationships with Daiichi Sankyo, Pfizer, Rigel, Autolus, Amgen, Servier, Takeda, Orum, Menarini, Remix, AbbVie, Astellas, BMS, Ibsen, Gilead, Genentech, and AstraZeneca. Dr. Wang discloses ties with AbbVie, Astellas, BMS, CTI Biopharma, Daiichi Sankyo, Gilead, GSK, Johnson & Johnson, Kite, Kura, Novartis, Pfizer, Rigel, Sellas, and Sumitomo Pharma. Dr. Grieselhuber has no disclosures.
“We went almost 3 decades with nothing, then all of a sudden we’ve had nine approvals in 5 or 6 years,” said Harvard Medical School, Boston, leukemia specialist Amir Fathi, MD, in an interview. “We’ve had a lot of advancement and a number of good options emerge.”
However, Dr. Fathi and other hematologists cautioned that the treatment landscape is becoming more complex to navigate. And they noted that prognoses for many older patients with AML remain grim. The expensive new treatments may only extend their lifespans by a matter of months, although some are surviving for years.
As the specialists explained, there are a variety of reasons why AML is especially difficult to treat.
“AML is one of the fastest growing human cancers, with tumor cell doubling times measured in mere hours in some patients. Therefore patients can present critically ill with white blood cell counts in the [hundreds of thousands of white blood cells per microliter instead of the normal range of 4,000-11,000]," said leukemia specialist Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y. “Because blood cells are found in every organ of the body, the sheer volume of rapidly growing cancer cells can overwhelm multiple organ systems in a very short amount of time. These rapid growing cells and the fact that the median age of diagnosis with AML is 67-70 years old makes this a clinically challenging cancer to treat. Chemotherapy strong enough to kill cancer cells run the risk of also harming the patient as well.”
Also, older patients often have comorbidities, and they face risks of infection from both the disease and its treatments, said AML specialist Nicole R. Grieselhuber, MD, PhD, of the Ohio State University, Columbus, in an interview.
Enter targeted therapy, which “has allowed individuals who previously were not candidates for cytotoxic chemotherapy because of their age or possible toxicities to receive effective therapy for AML,” Dr. Wang said. “Therapy directed at specific biological features of AML cells such as mutations (FLT3, IDH1, IDH2) or surface proteins (CD33) can augment the efficacy of conventional chemotherapy or in some cases (i.e., FLT3 inhibitors) be more effective than chemotherapy in controlling AML.”
Targeted therapy drugs “are expected to more selectively kill cancer cells and spare normal counterparts,” she added.
The FDA has approved nine targeted therapy drugs for AML in the last few years.
Retinoic acid and arsenic trioxide therapy for acute promyelocytic leukemia “has transformed this AML subtype into one of the most curable AML diseases,” Dr. Wang said. A 2017 long-term analysis of the drug combination found that complete remission was reached in 96% of 54 high-risk patients and 133 low-risk patients; the 5-year survival rate was 88%. (Some patients also received gemtuzumab ozogamicin, a CD33 antibody-drug conjugate.)
According to Dr. Wang, three FLT3 inhibitors have been approved for AML with the FLT3 mutation: midostaurin and quizartinib in the frontline setting in conjunction with intensive chemotherapy and gilteritinib for relapsed/refractory FLT3-mutant AML.
A 2017 study linked midostaurin plus chemotherapy to longer survival (hazard ratio for death = 0.78; P = .009), versus placebo plus chemotherapy, in patients aged 18-59. This year, a phase 3 randomized trial of quizartinib versus placebo linked the drug to longer survival median overall (31.9 months versus 15.1 months; P = .032) In a 2019 trial, patients who took gilteritinib had longer median overall survival (9.3 months versus 5.6 months; HR for death = 0.64; P < .001).
The success of these treatments “has led FLT3 mutant AML to be reclassified from a poor risk AML subtype to intermediate risk AML,” Dr. Wang said.
A 2022 report about FLT3 inhibitors cautioned, however, that “several drug resistance mechanisms have been identified” and added that “the benefit of FLT3 inhibitor maintenance therapy, either post chemotherapy or post transplant, remains controversial, although several studies are ongoing.”
Gemtuzumab ozogamicin is a monoclonal antibody connected to a chemotherapy drug, according to the American Cancer Society. “The addition of gemtuzumab ozogamicin to intensive chemotherapy has enhanced outcomes of favorable and intermediate risk disease,” Dr. Wang said.
Ivosidenib, olutasidenib, and enasidenib target the IDH1 or IDH2 genes in ADL. “These drugs seem to work by helping the leukemia cells mature (differentiate) into more normal cells,” according to the American Cancer Society. “Because of this, they are sometimes referred to as differentiation agents.”
In older adults, a combination treatment with venetoclax, a BCL-2 inhibitor, and a hypomethylating agent has become standard, Ohio State’s Dr. Grieselhuber said. The treatment is FDA approved.
There are caveats to targeted therapy in AML. The treatments can be enormously expensive, “and even patients with insurance are often shocked by the copay,” Dr. Grieselhuber said. It helps to work with pharmacists, social workers, or nurse navigators to help patients afford the treatments, she said.
Side effects vary by therapy and can include QT elongation and differentiation syndrome.
Most challenging of all, many AML patients still face shortened lifespans even if new treatments are available for them.
“Typically for older patients with AML, the lifespan of patients with therapy was 5-7 months and without therapy was 2-3 months,” Dr. Wang said. “Now, with regimens specifically designed for elderly and/or unfit subjects, many individuals are now routinely living more than a year: 14-18 months to 3-4 years.”
But “the vast majority of AML patients will still die of their disease with overall 5-year outcomes still less than 30% in all age categories,” she said. In addition, “fewer than 50% of AML patients are eligible for treatment with FDA-approved targeted therapies, as their disease biology does not express the mutation or protein needed for efficacy.”
Still, she said, “this represents a vast improvement.” And, she added, “in younger individuals, the combination of chemotherapy followed by allogeneic transplant has now permitted more of these individuals to be cured of their disease.” Dr. Grieselhuber noted that transplants are now considered appropriate even for patients in their 60s or early 70s, and they can be combined with targeted therapy.
Dr. Grieselhuber urged colleagues to keep in mind that quality-of-life preferences will play a role in some patient choices. For example, a elderly patient may reject burdensome infusion therapy and choose a pill instead, even if it has less efficacy. “There’s really no one-size-fits-all,” she said.
And, she added, it can be difficult to make choices about treatment because of the lack of randomized, head-to-head data regarding new therapies.
What’s on the horizon? Dr. Wang highlighted a novel class of targeted therapies called menin inhibitors for patients with NPM1-mutated AML, which she said accounts for one-third of patients with the disease. A treatment targeting disease in the 5%-10% patients with the KMT2A gene is also in the works, she said.
For now, Dr. Wang said it’s essential for clinicians “to perform timely comprehensive molecular and genomic tests on all AML patients at diagnosis and relapse to determine which individuals would benefit from targeted therapy versus cytotoxic chemotherapy. And participation in clinical trials at every stage of AML therapy can help accelerate clinical development of new agents for this disease.”
Dr. Fathi discloses relationships with Daiichi Sankyo, Pfizer, Rigel, Autolus, Amgen, Servier, Takeda, Orum, Menarini, Remix, AbbVie, Astellas, BMS, Ibsen, Gilead, Genentech, and AstraZeneca. Dr. Wang discloses ties with AbbVie, Astellas, BMS, CTI Biopharma, Daiichi Sankyo, Gilead, GSK, Johnson & Johnson, Kite, Kura, Novartis, Pfizer, Rigel, Sellas, and Sumitomo Pharma. Dr. Grieselhuber has no disclosures.
“We went almost 3 decades with nothing, then all of a sudden we’ve had nine approvals in 5 or 6 years,” said Harvard Medical School, Boston, leukemia specialist Amir Fathi, MD, in an interview. “We’ve had a lot of advancement and a number of good options emerge.”
However, Dr. Fathi and other hematologists cautioned that the treatment landscape is becoming more complex to navigate. And they noted that prognoses for many older patients with AML remain grim. The expensive new treatments may only extend their lifespans by a matter of months, although some are surviving for years.
As the specialists explained, there are a variety of reasons why AML is especially difficult to treat.
“AML is one of the fastest growing human cancers, with tumor cell doubling times measured in mere hours in some patients. Therefore patients can present critically ill with white blood cell counts in the [hundreds of thousands of white blood cells per microliter instead of the normal range of 4,000-11,000]," said leukemia specialist Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y. “Because blood cells are found in every organ of the body, the sheer volume of rapidly growing cancer cells can overwhelm multiple organ systems in a very short amount of time. These rapid growing cells and the fact that the median age of diagnosis with AML is 67-70 years old makes this a clinically challenging cancer to treat. Chemotherapy strong enough to kill cancer cells run the risk of also harming the patient as well.”
Also, older patients often have comorbidities, and they face risks of infection from both the disease and its treatments, said AML specialist Nicole R. Grieselhuber, MD, PhD, of the Ohio State University, Columbus, in an interview.
Enter targeted therapy, which “has allowed individuals who previously were not candidates for cytotoxic chemotherapy because of their age or possible toxicities to receive effective therapy for AML,” Dr. Wang said. “Therapy directed at specific biological features of AML cells such as mutations (FLT3, IDH1, IDH2) or surface proteins (CD33) can augment the efficacy of conventional chemotherapy or in some cases (i.e., FLT3 inhibitors) be more effective than chemotherapy in controlling AML.”
Targeted therapy drugs “are expected to more selectively kill cancer cells and spare normal counterparts,” she added.
The FDA has approved nine targeted therapy drugs for AML in the last few years.
Retinoic acid and arsenic trioxide therapy for acute promyelocytic leukemia “has transformed this AML subtype into one of the most curable AML diseases,” Dr. Wang said. A 2017 long-term analysis of the drug combination found that complete remission was reached in 96% of 54 high-risk patients and 133 low-risk patients; the 5-year survival rate was 88%. (Some patients also received gemtuzumab ozogamicin, a CD33 antibody-drug conjugate.)
According to Dr. Wang, three FLT3 inhibitors have been approved for AML with the FLT3 mutation: midostaurin and quizartinib in the frontline setting in conjunction with intensive chemotherapy and gilteritinib for relapsed/refractory FLT3-mutant AML.
A 2017 study linked midostaurin plus chemotherapy to longer survival (hazard ratio for death = 0.78; P = .009), versus placebo plus chemotherapy, in patients aged 18-59. This year, a phase 3 randomized trial of quizartinib versus placebo linked the drug to longer survival median overall (31.9 months versus 15.1 months; P = .032) In a 2019 trial, patients who took gilteritinib had longer median overall survival (9.3 months versus 5.6 months; HR for death = 0.64; P < .001).
The success of these treatments “has led FLT3 mutant AML to be reclassified from a poor risk AML subtype to intermediate risk AML,” Dr. Wang said.
A 2022 report about FLT3 inhibitors cautioned, however, that “several drug resistance mechanisms have been identified” and added that “the benefit of FLT3 inhibitor maintenance therapy, either post chemotherapy or post transplant, remains controversial, although several studies are ongoing.”
Gemtuzumab ozogamicin is a monoclonal antibody connected to a chemotherapy drug, according to the American Cancer Society. “The addition of gemtuzumab ozogamicin to intensive chemotherapy has enhanced outcomes of favorable and intermediate risk disease,” Dr. Wang said.
Ivosidenib, olutasidenib, and enasidenib target the IDH1 or IDH2 genes in ADL. “These drugs seem to work by helping the leukemia cells mature (differentiate) into more normal cells,” according to the American Cancer Society. “Because of this, they are sometimes referred to as differentiation agents.”
In older adults, a combination treatment with venetoclax, a BCL-2 inhibitor, and a hypomethylating agent has become standard, Ohio State’s Dr. Grieselhuber said. The treatment is FDA approved.
There are caveats to targeted therapy in AML. The treatments can be enormously expensive, “and even patients with insurance are often shocked by the copay,” Dr. Grieselhuber said. It helps to work with pharmacists, social workers, or nurse navigators to help patients afford the treatments, she said.
Side effects vary by therapy and can include QT elongation and differentiation syndrome.
Most challenging of all, many AML patients still face shortened lifespans even if new treatments are available for them.
“Typically for older patients with AML, the lifespan of patients with therapy was 5-7 months and without therapy was 2-3 months,” Dr. Wang said. “Now, with regimens specifically designed for elderly and/or unfit subjects, many individuals are now routinely living more than a year: 14-18 months to 3-4 years.”
But “the vast majority of AML patients will still die of their disease with overall 5-year outcomes still less than 30% in all age categories,” she said. In addition, “fewer than 50% of AML patients are eligible for treatment with FDA-approved targeted therapies, as their disease biology does not express the mutation or protein needed for efficacy.”
Still, she said, “this represents a vast improvement.” And, she added, “in younger individuals, the combination of chemotherapy followed by allogeneic transplant has now permitted more of these individuals to be cured of their disease.” Dr. Grieselhuber noted that transplants are now considered appropriate even for patients in their 60s or early 70s, and they can be combined with targeted therapy.
Dr. Grieselhuber urged colleagues to keep in mind that quality-of-life preferences will play a role in some patient choices. For example, a elderly patient may reject burdensome infusion therapy and choose a pill instead, even if it has less efficacy. “There’s really no one-size-fits-all,” she said.
And, she added, it can be difficult to make choices about treatment because of the lack of randomized, head-to-head data regarding new therapies.
What’s on the horizon? Dr. Wang highlighted a novel class of targeted therapies called menin inhibitors for patients with NPM1-mutated AML, which she said accounts for one-third of patients with the disease. A treatment targeting disease in the 5%-10% patients with the KMT2A gene is also in the works, she said.
For now, Dr. Wang said it’s essential for clinicians “to perform timely comprehensive molecular and genomic tests on all AML patients at diagnosis and relapse to determine which individuals would benefit from targeted therapy versus cytotoxic chemotherapy. And participation in clinical trials at every stage of AML therapy can help accelerate clinical development of new agents for this disease.”
Dr. Fathi discloses relationships with Daiichi Sankyo, Pfizer, Rigel, Autolus, Amgen, Servier, Takeda, Orum, Menarini, Remix, AbbVie, Astellas, BMS, Ibsen, Gilead, Genentech, and AstraZeneca. Dr. Wang discloses ties with AbbVie, Astellas, BMS, CTI Biopharma, Daiichi Sankyo, Gilead, GSK, Johnson & Johnson, Kite, Kura, Novartis, Pfizer, Rigel, Sellas, and Sumitomo Pharma. Dr. Grieselhuber has no disclosures.
Trial halted for bleeding reduction with abelacimab vs. rivaroxaban in AFib
– major and clinically relevant nonmajor bleeding – in patients taking abelacimab versus those on rivaroxaban.
The announcement of topline results of the AZALEA-TIMI 71 trial was made by Anthos Therapeutics, the company developing abelacimab.
“The AZALEA-TIMI 71 study is the largest and longest head-to-head study of a Factor XI inhibitor to provide definitive evidence of a highly significant reduction in bleeding as compared to the standard-of-care anticoagulant,” Marc Sabatine, MD, chair of cardiovascular medicine at Brigham and Women’s Hospital and chair of the TIMI study group, both in Boston, stated in the Anthos press release.
“With a median of 21 months of follow-up, spanning more than 2,000 patient years, AZALEA-TIMI 71 represents a landmark study confirming the promise of Factor XI inhibition as causing substantially less bleeding than a current standard-of-care,” Dr. Sabatine added.
Abelacimab is a novel, highly selective, fully human monoclonal antibody with dual inhibitory activity against factor XI and its active form, factor XIa. At the 150-mg dose given subcutaneously once monthly, the drug maintains around 98% inhibition of factor XI, in line with the benign bleeding profile of patients with genetic factor XI deficiency, the company notes.
The AZALEA-TIMI 71 study is an event-driven, randomized study comparing two blinded doses of abelacimab (90 mg or 150 mg given by subcutaneous injection once-monthly) with rivaroxaban 20 mg daily in 1,287 patients with AFib who are at moderate to high risk for stroke. Full results of the study will be presented at an upcoming scientific congress.
Patients in the rivaroxaban arm can transition to abelacimab in an extension study.
In a previous proof-of-concept study published in The New England Journal of Medicine, a single IV dose of abelacimab achieved a large reduction in venous thromboembolism versus enoxaparin in patients undergoing knee surgery.
A phase 3 trial in AFib patients is now planned. The LILAC-TIMI 76 study is an event-driven, randomized trial to evaluate the efficacy and safety of abelacimab relative to placebo on the rate of ischemic stroke or systemic embolism in AFib patients who have been deemed to be unsuitable for currently available anticoagulation therapy. Patients will be randomized to receive abelacimab 150 mg subcutaneously or matching placebo once monthly. The researchers aim to enroll approximately 1,900 patients from North America, Europe, Latin America, the Middle East, and Asia.
Dan Bloomfield, MD, chief medical officer of Anthos Therapeutics, said that, “Abelacimab embodies its promise as a hemostasis-sparing anticoagulant and represents a paradigm shift in the prevention of stroke and other thrombotic conditions.”
It is estimated that 12.1 million people in the United States will have AFib by 2030, but 40%-60% of patients with AFib are not prescribed anticoagulants today, one of the main reasons being concerns about bleeding, the company notes.
“Abelacimab has the potential to provide a game-changing treatment option for all those patients who live with the daily fear of bleeding while taking current anticoagulants,” said Leslie Lake, president of the National Blood Clot Alliance.
Abelacimab has been granted a fast-track designation by the U.S. Food and Drug Administration for the prevention of stroke and systemic embolism in patients with atrial fibrillation.
Several other Factor XI inhibitors are in development and have also shown promising results in terms of a more benign bleeding profile than current standard-of-care anticoagulants.
A version of this article first appeared on Medscape.com.
– major and clinically relevant nonmajor bleeding – in patients taking abelacimab versus those on rivaroxaban.
The announcement of topline results of the AZALEA-TIMI 71 trial was made by Anthos Therapeutics, the company developing abelacimab.
“The AZALEA-TIMI 71 study is the largest and longest head-to-head study of a Factor XI inhibitor to provide definitive evidence of a highly significant reduction in bleeding as compared to the standard-of-care anticoagulant,” Marc Sabatine, MD, chair of cardiovascular medicine at Brigham and Women’s Hospital and chair of the TIMI study group, both in Boston, stated in the Anthos press release.
“With a median of 21 months of follow-up, spanning more than 2,000 patient years, AZALEA-TIMI 71 represents a landmark study confirming the promise of Factor XI inhibition as causing substantially less bleeding than a current standard-of-care,” Dr. Sabatine added.
Abelacimab is a novel, highly selective, fully human monoclonal antibody with dual inhibitory activity against factor XI and its active form, factor XIa. At the 150-mg dose given subcutaneously once monthly, the drug maintains around 98% inhibition of factor XI, in line with the benign bleeding profile of patients with genetic factor XI deficiency, the company notes.
The AZALEA-TIMI 71 study is an event-driven, randomized study comparing two blinded doses of abelacimab (90 mg or 150 mg given by subcutaneous injection once-monthly) with rivaroxaban 20 mg daily in 1,287 patients with AFib who are at moderate to high risk for stroke. Full results of the study will be presented at an upcoming scientific congress.
Patients in the rivaroxaban arm can transition to abelacimab in an extension study.
In a previous proof-of-concept study published in The New England Journal of Medicine, a single IV dose of abelacimab achieved a large reduction in venous thromboembolism versus enoxaparin in patients undergoing knee surgery.
A phase 3 trial in AFib patients is now planned. The LILAC-TIMI 76 study is an event-driven, randomized trial to evaluate the efficacy and safety of abelacimab relative to placebo on the rate of ischemic stroke or systemic embolism in AFib patients who have been deemed to be unsuitable for currently available anticoagulation therapy. Patients will be randomized to receive abelacimab 150 mg subcutaneously or matching placebo once monthly. The researchers aim to enroll approximately 1,900 patients from North America, Europe, Latin America, the Middle East, and Asia.
Dan Bloomfield, MD, chief medical officer of Anthos Therapeutics, said that, “Abelacimab embodies its promise as a hemostasis-sparing anticoagulant and represents a paradigm shift in the prevention of stroke and other thrombotic conditions.”
It is estimated that 12.1 million people in the United States will have AFib by 2030, but 40%-60% of patients with AFib are not prescribed anticoagulants today, one of the main reasons being concerns about bleeding, the company notes.
“Abelacimab has the potential to provide a game-changing treatment option for all those patients who live with the daily fear of bleeding while taking current anticoagulants,” said Leslie Lake, president of the National Blood Clot Alliance.
Abelacimab has been granted a fast-track designation by the U.S. Food and Drug Administration for the prevention of stroke and systemic embolism in patients with atrial fibrillation.
Several other Factor XI inhibitors are in development and have also shown promising results in terms of a more benign bleeding profile than current standard-of-care anticoagulants.
A version of this article first appeared on Medscape.com.
– major and clinically relevant nonmajor bleeding – in patients taking abelacimab versus those on rivaroxaban.
The announcement of topline results of the AZALEA-TIMI 71 trial was made by Anthos Therapeutics, the company developing abelacimab.
“The AZALEA-TIMI 71 study is the largest and longest head-to-head study of a Factor XI inhibitor to provide definitive evidence of a highly significant reduction in bleeding as compared to the standard-of-care anticoagulant,” Marc Sabatine, MD, chair of cardiovascular medicine at Brigham and Women’s Hospital and chair of the TIMI study group, both in Boston, stated in the Anthos press release.
“With a median of 21 months of follow-up, spanning more than 2,000 patient years, AZALEA-TIMI 71 represents a landmark study confirming the promise of Factor XI inhibition as causing substantially less bleeding than a current standard-of-care,” Dr. Sabatine added.
Abelacimab is a novel, highly selective, fully human monoclonal antibody with dual inhibitory activity against factor XI and its active form, factor XIa. At the 150-mg dose given subcutaneously once monthly, the drug maintains around 98% inhibition of factor XI, in line with the benign bleeding profile of patients with genetic factor XI deficiency, the company notes.
The AZALEA-TIMI 71 study is an event-driven, randomized study comparing two blinded doses of abelacimab (90 mg or 150 mg given by subcutaneous injection once-monthly) with rivaroxaban 20 mg daily in 1,287 patients with AFib who are at moderate to high risk for stroke. Full results of the study will be presented at an upcoming scientific congress.
Patients in the rivaroxaban arm can transition to abelacimab in an extension study.
In a previous proof-of-concept study published in The New England Journal of Medicine, a single IV dose of abelacimab achieved a large reduction in venous thromboembolism versus enoxaparin in patients undergoing knee surgery.
A phase 3 trial in AFib patients is now planned. The LILAC-TIMI 76 study is an event-driven, randomized trial to evaluate the efficacy and safety of abelacimab relative to placebo on the rate of ischemic stroke or systemic embolism in AFib patients who have been deemed to be unsuitable for currently available anticoagulation therapy. Patients will be randomized to receive abelacimab 150 mg subcutaneously or matching placebo once monthly. The researchers aim to enroll approximately 1,900 patients from North America, Europe, Latin America, the Middle East, and Asia.
Dan Bloomfield, MD, chief medical officer of Anthos Therapeutics, said that, “Abelacimab embodies its promise as a hemostasis-sparing anticoagulant and represents a paradigm shift in the prevention of stroke and other thrombotic conditions.”
It is estimated that 12.1 million people in the United States will have AFib by 2030, but 40%-60% of patients with AFib are not prescribed anticoagulants today, one of the main reasons being concerns about bleeding, the company notes.
“Abelacimab has the potential to provide a game-changing treatment option for all those patients who live with the daily fear of bleeding while taking current anticoagulants,” said Leslie Lake, president of the National Blood Clot Alliance.
Abelacimab has been granted a fast-track designation by the U.S. Food and Drug Administration for the prevention of stroke and systemic embolism in patients with atrial fibrillation.
Several other Factor XI inhibitors are in development and have also shown promising results in terms of a more benign bleeding profile than current standard-of-care anticoagulants.
A version of this article first appeared on Medscape.com.
Nationwide hematologists shortage: What’s being done?
Over decades, the shrinking pool of CHs – who are compensated far less than hematologist-oncologists – has put patients at risk without access to adequate and timely care. To alleviate this crisis, individual doctors and national organizations are taking action and making more resources available to CHs and their patients.
`Vicious cycle’
The root cause of the CH shortage can be traced to a dramatic reduction in the number of physicians trained in this field, as Leonard Valentino, MD, President of the National Bleeding Disorders Foundation in New York, explained in an interview.
“There is a vicious cycle where there’s not enough classical hematologists to be program directors, and therefore trainees are often steered to fellowships in oncology,” said Dr. Valentino.
According to data published in JAMA, in 1995 there were 74 classical hematology programs in the United States; by 2018, there were only 2, During this same time period, the number of combined hematology/oncology training programs (HOPs) nearly doubled, from 75 to 146. However, it is estimated that less than 5% of graduates of adult HOPs pursued a career in classical hematology, as reported in Blood Advances. This low percentage can be attributed, at least in part, to the emphasis that most HOPs place on oncology.
Dr. Valentino noted that financial pressures are also diverting medical students from becoming CHs, adding that a hematologist-oncologist can make three times the annual salary of a CH.
Furthermore, when CHs treat bleeding and clotting disorders, they often need to meet with a patient for a 60- to 90-minute initial consultation, then they go on to provide a lifetime of labor-intensive care.
“This work is neither verticalized [that is, supported by radiologists, surgeons, and a cadre of nurses], nor is it billable per hour on a scale comparable to what oncologists can charge,” Dr. Valentino explained.
The survey published in Blood Advances illustrates the consequences of such a disparity in income potential: 34% of hematology/oncology fellows surveyed were likely to enter solid tumor oncology, while 20% and 4.6% would proceed to malignant hematology and CH, respectively.
Toll on patients
Primary care doctors treat some common blood disorders, but they almost always refer more difficult or complicated cases to a shrinking population of CHs.
“For many Americans, it is getting more difficult to find providers who subspecialize in hemostasis and thrombosis disorders. Patients can expect prolonged waiting times to get evaluated after a referral” said Mukul Singal, MD, of the Indiana Hemophilia and Thrombosis Center in Indianapolis.
Dr. Singal said the shortage is so acute that “at many institutions, malignant hematologists or oncologists are having to staff in-patient hematology consult services and see outpatient classical hematology patients. General hematologist/oncologists or medical oncologists are often not as comfortable or experienced with dealing with some of the complex CH conditions.”
A working care model, without enough doctors
In 1975, responding to patient advocacy groups, the federal government began funding hemophilia treatment centers (HTCs). Such centers offer a comprehensive care model that gives patients access to practitioners and administrative staff with the expertise to help them stay as healthy as possible. According to the Centers for Disease Control and Prevention, people with hemophilia who used an HTC were 40% less likely to die of a hemophilia-related complication and 40% less likely to be hospitalized for bleeding complications, compared to those who did not receive such specialized care.
“HTCs are effective at keeping patients out of the hospital and engaged in their lives. Between 80% and 95% of hemophilia patients get their care from an HTC and more patients want more services from them,” said Joe Pugliese, president of the Hemophilia Alliance in Lansdale, Pa.
Expanding care to meet patient demand is challenged by the restrictions on doctors’ salaries. All 140 U.S.-based HTCs share a $4.9 million federal grant but, by law, they can’t pay any provider more than $211,000 a year. “These restrictions push many people to industry, leaving too few doctors to meet patient demand,” Mr. Pugliese explained.
The fact that most HTCs are located in or near major cities also presents patients with the challenge of commuting, sometimes across state lines, to see a specialist. However, an uptick in telemedicine has provided one bright spot for many patients, allowing care to be brought to them.
The Hemophilia Alliance is also working on a multifaceted approach to change the rules, so that CHs are offered better compensation. “We have lobbyists in Washington, as well as an advocacy committee and a payer committee working to better support the HTC model,” Mr. Pugliese said.
Beyond the paycheck: Supporting CHs and patients
As market and regulatory restrictions make it difficult to boost the pay of CHs, doctors and nonprofit organizations are collaborating to support young CHs and bring more into the field. The American Society of Hematology has started and fully funded the Hematology Focused Fellowship Training Program (HFFTP). This program pairs comprehensive classical hematology training with education in transfusion medicine, sickle cell disease, hemostasis/thrombosis, systems-based hematology, health equity research, and global health. According to the program’s website, HFFTP’s goal is to add 50 new academic hematologists nationwide by 2030, in an effort to “improve the lives of patients with blood and bone marrow disorders.”
Additionally, classic hematologists are aiming to attract younger physicians and trainees to their field by introducing them to the various rewarding aspects of dealing with patients with inherited, chronic blood diseases. Programs like the Partners Physicians Academy (PPA), a 5-day training course that is specifically designed to encourage and retain young hematology students as classical hematologists, are essential to this effort.
“Along with preparing physicians to work in an HTC, programs like the Hematology Focused Fellowship Training Program and the Partners Physicians Academy are so important because they might convince young doctors to stick with non–oncology-based hematology careers, through the right mix of knowing about exciting research like gene therapy, financial and mentorship support, and a desire to meet unmet medical need,” explained Dr. Valentino.
The next PPA is taking place Sept. 18-22 in Indianapolis.
Dr. Singal, Dr. Valentino, and Mr. Pugliese had no financial disclosures to report.
Over decades, the shrinking pool of CHs – who are compensated far less than hematologist-oncologists – has put patients at risk without access to adequate and timely care. To alleviate this crisis, individual doctors and national organizations are taking action and making more resources available to CHs and their patients.
`Vicious cycle’
The root cause of the CH shortage can be traced to a dramatic reduction in the number of physicians trained in this field, as Leonard Valentino, MD, President of the National Bleeding Disorders Foundation in New York, explained in an interview.
“There is a vicious cycle where there’s not enough classical hematologists to be program directors, and therefore trainees are often steered to fellowships in oncology,” said Dr. Valentino.
According to data published in JAMA, in 1995 there were 74 classical hematology programs in the United States; by 2018, there were only 2, During this same time period, the number of combined hematology/oncology training programs (HOPs) nearly doubled, from 75 to 146. However, it is estimated that less than 5% of graduates of adult HOPs pursued a career in classical hematology, as reported in Blood Advances. This low percentage can be attributed, at least in part, to the emphasis that most HOPs place on oncology.
Dr. Valentino noted that financial pressures are also diverting medical students from becoming CHs, adding that a hematologist-oncologist can make three times the annual salary of a CH.
Furthermore, when CHs treat bleeding and clotting disorders, they often need to meet with a patient for a 60- to 90-minute initial consultation, then they go on to provide a lifetime of labor-intensive care.
“This work is neither verticalized [that is, supported by radiologists, surgeons, and a cadre of nurses], nor is it billable per hour on a scale comparable to what oncologists can charge,” Dr. Valentino explained.
The survey published in Blood Advances illustrates the consequences of such a disparity in income potential: 34% of hematology/oncology fellows surveyed were likely to enter solid tumor oncology, while 20% and 4.6% would proceed to malignant hematology and CH, respectively.
Toll on patients
Primary care doctors treat some common blood disorders, but they almost always refer more difficult or complicated cases to a shrinking population of CHs.
“For many Americans, it is getting more difficult to find providers who subspecialize in hemostasis and thrombosis disorders. Patients can expect prolonged waiting times to get evaluated after a referral” said Mukul Singal, MD, of the Indiana Hemophilia and Thrombosis Center in Indianapolis.
Dr. Singal said the shortage is so acute that “at many institutions, malignant hematologists or oncologists are having to staff in-patient hematology consult services and see outpatient classical hematology patients. General hematologist/oncologists or medical oncologists are often not as comfortable or experienced with dealing with some of the complex CH conditions.”
A working care model, without enough doctors
In 1975, responding to patient advocacy groups, the federal government began funding hemophilia treatment centers (HTCs). Such centers offer a comprehensive care model that gives patients access to practitioners and administrative staff with the expertise to help them stay as healthy as possible. According to the Centers for Disease Control and Prevention, people with hemophilia who used an HTC were 40% less likely to die of a hemophilia-related complication and 40% less likely to be hospitalized for bleeding complications, compared to those who did not receive such specialized care.
“HTCs are effective at keeping patients out of the hospital and engaged in their lives. Between 80% and 95% of hemophilia patients get their care from an HTC and more patients want more services from them,” said Joe Pugliese, president of the Hemophilia Alliance in Lansdale, Pa.
Expanding care to meet patient demand is challenged by the restrictions on doctors’ salaries. All 140 U.S.-based HTCs share a $4.9 million federal grant but, by law, they can’t pay any provider more than $211,000 a year. “These restrictions push many people to industry, leaving too few doctors to meet patient demand,” Mr. Pugliese explained.
The fact that most HTCs are located in or near major cities also presents patients with the challenge of commuting, sometimes across state lines, to see a specialist. However, an uptick in telemedicine has provided one bright spot for many patients, allowing care to be brought to them.
The Hemophilia Alliance is also working on a multifaceted approach to change the rules, so that CHs are offered better compensation. “We have lobbyists in Washington, as well as an advocacy committee and a payer committee working to better support the HTC model,” Mr. Pugliese said.
Beyond the paycheck: Supporting CHs and patients
As market and regulatory restrictions make it difficult to boost the pay of CHs, doctors and nonprofit organizations are collaborating to support young CHs and bring more into the field. The American Society of Hematology has started and fully funded the Hematology Focused Fellowship Training Program (HFFTP). This program pairs comprehensive classical hematology training with education in transfusion medicine, sickle cell disease, hemostasis/thrombosis, systems-based hematology, health equity research, and global health. According to the program’s website, HFFTP’s goal is to add 50 new academic hematologists nationwide by 2030, in an effort to “improve the lives of patients with blood and bone marrow disorders.”
Additionally, classic hematologists are aiming to attract younger physicians and trainees to their field by introducing them to the various rewarding aspects of dealing with patients with inherited, chronic blood diseases. Programs like the Partners Physicians Academy (PPA), a 5-day training course that is specifically designed to encourage and retain young hematology students as classical hematologists, are essential to this effort.
“Along with preparing physicians to work in an HTC, programs like the Hematology Focused Fellowship Training Program and the Partners Physicians Academy are so important because they might convince young doctors to stick with non–oncology-based hematology careers, through the right mix of knowing about exciting research like gene therapy, financial and mentorship support, and a desire to meet unmet medical need,” explained Dr. Valentino.
The next PPA is taking place Sept. 18-22 in Indianapolis.
Dr. Singal, Dr. Valentino, and Mr. Pugliese had no financial disclosures to report.
Over decades, the shrinking pool of CHs – who are compensated far less than hematologist-oncologists – has put patients at risk without access to adequate and timely care. To alleviate this crisis, individual doctors and national organizations are taking action and making more resources available to CHs and their patients.
`Vicious cycle’
The root cause of the CH shortage can be traced to a dramatic reduction in the number of physicians trained in this field, as Leonard Valentino, MD, President of the National Bleeding Disorders Foundation in New York, explained in an interview.
“There is a vicious cycle where there’s not enough classical hematologists to be program directors, and therefore trainees are often steered to fellowships in oncology,” said Dr. Valentino.
According to data published in JAMA, in 1995 there were 74 classical hematology programs in the United States; by 2018, there were only 2, During this same time period, the number of combined hematology/oncology training programs (HOPs) nearly doubled, from 75 to 146. However, it is estimated that less than 5% of graduates of adult HOPs pursued a career in classical hematology, as reported in Blood Advances. This low percentage can be attributed, at least in part, to the emphasis that most HOPs place on oncology.
Dr. Valentino noted that financial pressures are also diverting medical students from becoming CHs, adding that a hematologist-oncologist can make three times the annual salary of a CH.
Furthermore, when CHs treat bleeding and clotting disorders, they often need to meet with a patient for a 60- to 90-minute initial consultation, then they go on to provide a lifetime of labor-intensive care.
“This work is neither verticalized [that is, supported by radiologists, surgeons, and a cadre of nurses], nor is it billable per hour on a scale comparable to what oncologists can charge,” Dr. Valentino explained.
The survey published in Blood Advances illustrates the consequences of such a disparity in income potential: 34% of hematology/oncology fellows surveyed were likely to enter solid tumor oncology, while 20% and 4.6% would proceed to malignant hematology and CH, respectively.
Toll on patients
Primary care doctors treat some common blood disorders, but they almost always refer more difficult or complicated cases to a shrinking population of CHs.
“For many Americans, it is getting more difficult to find providers who subspecialize in hemostasis and thrombosis disorders. Patients can expect prolonged waiting times to get evaluated after a referral” said Mukul Singal, MD, of the Indiana Hemophilia and Thrombosis Center in Indianapolis.
Dr. Singal said the shortage is so acute that “at many institutions, malignant hematologists or oncologists are having to staff in-patient hematology consult services and see outpatient classical hematology patients. General hematologist/oncologists or medical oncologists are often not as comfortable or experienced with dealing with some of the complex CH conditions.”
A working care model, without enough doctors
In 1975, responding to patient advocacy groups, the federal government began funding hemophilia treatment centers (HTCs). Such centers offer a comprehensive care model that gives patients access to practitioners and administrative staff with the expertise to help them stay as healthy as possible. According to the Centers for Disease Control and Prevention, people with hemophilia who used an HTC were 40% less likely to die of a hemophilia-related complication and 40% less likely to be hospitalized for bleeding complications, compared to those who did not receive such specialized care.
“HTCs are effective at keeping patients out of the hospital and engaged in their lives. Between 80% and 95% of hemophilia patients get their care from an HTC and more patients want more services from them,” said Joe Pugliese, president of the Hemophilia Alliance in Lansdale, Pa.
Expanding care to meet patient demand is challenged by the restrictions on doctors’ salaries. All 140 U.S.-based HTCs share a $4.9 million federal grant but, by law, they can’t pay any provider more than $211,000 a year. “These restrictions push many people to industry, leaving too few doctors to meet patient demand,” Mr. Pugliese explained.
The fact that most HTCs are located in or near major cities also presents patients with the challenge of commuting, sometimes across state lines, to see a specialist. However, an uptick in telemedicine has provided one bright spot for many patients, allowing care to be brought to them.
The Hemophilia Alliance is also working on a multifaceted approach to change the rules, so that CHs are offered better compensation. “We have lobbyists in Washington, as well as an advocacy committee and a payer committee working to better support the HTC model,” Mr. Pugliese said.
Beyond the paycheck: Supporting CHs and patients
As market and regulatory restrictions make it difficult to boost the pay of CHs, doctors and nonprofit organizations are collaborating to support young CHs and bring more into the field. The American Society of Hematology has started and fully funded the Hematology Focused Fellowship Training Program (HFFTP). This program pairs comprehensive classical hematology training with education in transfusion medicine, sickle cell disease, hemostasis/thrombosis, systems-based hematology, health equity research, and global health. According to the program’s website, HFFTP’s goal is to add 50 new academic hematologists nationwide by 2030, in an effort to “improve the lives of patients with blood and bone marrow disorders.”
Additionally, classic hematologists are aiming to attract younger physicians and trainees to their field by introducing them to the various rewarding aspects of dealing with patients with inherited, chronic blood diseases. Programs like the Partners Physicians Academy (PPA), a 5-day training course that is specifically designed to encourage and retain young hematology students as classical hematologists, are essential to this effort.
“Along with preparing physicians to work in an HTC, programs like the Hematology Focused Fellowship Training Program and the Partners Physicians Academy are so important because they might convince young doctors to stick with non–oncology-based hematology careers, through the right mix of knowing about exciting research like gene therapy, financial and mentorship support, and a desire to meet unmet medical need,” explained Dr. Valentino.
The next PPA is taking place Sept. 18-22 in Indianapolis.
Dr. Singal, Dr. Valentino, and Mr. Pugliese had no financial disclosures to report.
Do doctors have a legal right to work from home because of health issues or disability?
A radiologist who claims he was forced to resign after requesting to work from home has settled his discrimination lawsuit with a New York hospital.
Although the case was resolved without a definitive win, legal analysts say the complaint raises important questions about whether some physicians have the right to work from home.
Since the pandemic, employers across the country have become more accepting of professionals working remotely.
Richard Heiden, MD, sued New York City Health and Hospitals in 2020, claiming discrimination and retaliation violations under the American with Disabilities Act (ADA) and the New York State Human Rights Law. Dr. Heiden, who has ulcerative colitis, had asked to work off-site during the start of the pandemic, but the hospital denied his accommodation request. Shortly later, administrators accused Dr. Heiden of poor performance and requested he resign or administrators would terminate him, according to his lawsuit.
Attorneys for New York City Health and Hospitals contended that Dr. Heiden was a poorly performing radiologist who was undergoing a performance review at the time of his accommodation request. The radiologist’s departure was related to the results of the review and had nothing to do with his disability or accommodation request, according to the hospital.
The undisclosed settlement ends a 3-year court battle between Dr. Heiden and the hospital corporation.
In an email, Laura Williams, an attorney for the hospital corporation, said that “the settlement was in the best interest of all parties.”
Dr. Heiden and his attorneys also did not respond to requests for comment.
A critical piece to the puzzle is understanding who is protected under the ADA and is therefore entitled to reasonable accommodations, said Doron Dorfman, JSD, an associate professor at Seton Hall University Law School in Newark, N.J., who focuses on disability law.
A common misconception is that only physicians with a physical disability are “disabled,” he said. However, under the law, a disabled individual is anyone with a physical or mental impairment – including mental illness – that limits major life activities; a person with a history of such impairment; or a person who is perceived by others as having an impairment.
“The law is much broader than many people think,” he said. “I think a lot of people don’t think about those with invisible disabilities, such as people with allergies, those who are immunocompromised, those with chronic illnesses. A lot of people don’t see themselves as disabled, and a lot of employers don’t see them as disabled.”
Working from home has not historically been considered a “reasonable accommodation” under the ADA, Mr. Dorfman said. However, that appears to be changing.
“There has been a sea change,” Mr. Dorfman said. “The question is coming before the courts more frequently, and recent legal decisions show judges may be altering their views on the subject.”
What led to the doctor’s lawsuit?
Dr. Heiden, a longtime radiologist, had practiced at Lincoln Medical and Mental Health Center for about a year when he requested to work remotely. (Lincoln is operated by New York City Health and Hospitals.) At the time, the governor of New York had ordered a statewide lockdown because of COVID-19, and Dr. Heiden expressed concern that his ulcerative colitis made him a high-risk individual for the virus, according to court documents.
In his March 22, 2020, request, Dr. Heiden said that, except for fluoroscopy, his job could be done entirely from his home, according to a district court summary of the case. He also offered to pay for any costs associated with the remote work setup.
Around the same time, New York City Health and Hospitals permitted its facilities to issue a limited number of workstations to radiologists to facilitate remote work in the event of COVID-related staffing shortages. Administrators were in the process of acquiring remote radiology workstations and determining which radiologists at Lincoln would receive them, according to the case summary.
On March 24, the chair of radiology at Lincoln met with Dr. Heiden to review the results of a recent focused professional practice evaluation (FPPE). An FPPE refers to an intensive review of an expansive selection of patient cases handled by the subject physician. During the meeting, the chair that claimed Dr. Heiden was a poor performer and was accurate in his assessments 93.8% of the time, which was below the hospital’s 97% threshold, according to Dr. Heiden’s lawsuit. Dr. Heiden disagreed with the results, and the two engaged in several more meetings.
Meanwhile, Dr. Heiden’s accommodation request was forwarded to other administrators. In an email introduced into court evidence, the chair indicated he did not support the accommodation, writing that Dr. Heiden’s “skill set does not meet the criteria for the initial installations” of the workstations.
On March 26, 2020, the chair allegedly asked Dr. Heiden to either resign or he would be terminated and reported to the New York State Office of Professional Medical Conduct. Four days later, Dr. Heiden learned that his accommodation request had been denied. He resigned on April 2, 2020.
In his lawsuit, Dr. Heiden claimed that the hospital discriminated against him on the basis of his disability in violation of ADA by denying him equal terms and conditions of employment and failing to provide a reasonable accommodation.
The defendants, who included the radiology chair, did not dispute that Dr. Heiden was asked to resign or that administrators warned termination, but they argued the impetus was his FPPE results and a history of inaccurate interpretations. Other clinicians and physicians had expressed concerns about Dr. Heiden’s “lack of clarity [and] interpretive errors,” according to deposition testimony. The hospital emphasized the FPPE had concluded before Dr. Heiden’s accommodation request was made.
New York City Health and Hospitals requested a federal judge dismiss the lawsuit for lack of valid claims. In January 2023, U.S. District Judge Lewis Liman allowed the case to proceed, ruling that some of Dr. Heiden’s claims had merit.
“Plaintiff has satisfied his obligation to proffer sufficient evidence to create an inference of retaliatory or discriminatory intent,” Judge Liman wrote in his decision. “[The chair] had not always planned to ask for plaintiff’s resignation based on the results of the FPPE completed on March 10, 2020. The decision to ask for that resignation arose shortly after the request for the accommodation. And there is evidence from which the jury could find that [the chair] was not receptive to making the accommodation.”
A jury trial was scheduled for July 2023, but the parties reached a settlement on May 31, 2023.
Is working from home reasonable for physicians?
The widespread swing to remote work in recent years has paved a smoother road for physicians who request the accommodation, said Peter Poullos, MD, clinical associate professor of radiology, gastroenterology, and hepatology at Stanford (Calif.) University and founder and cochair of the Stanford Medicine Alliance for Disability Inclusion and Equity.
“There is now a precedent and examples all over that working from home for some is a viable alternative to working in the hospital or a clinic,” Dr. Poullos said. “If a lawyer can point to instances of other people having received the same accommodation, even if the accommodation was given to someone without a disability, it’s much harder for an employer to say: ‘It’s not possible.’ Because clearly, it is.”
A key factor is the employee’s job duties and whether the employee can complete them remotely, said Mr. Dorfman. With physicians, the reasonableness would heavily depend on their specialty.
A radiologist, for example, would probably have a stronger case for performing their duties remotely compared with a surgeon, Dr. Poullos said.
In general, whether an accommodation is reasonable is decided on a case-by-case basis and usually includes reviewing supporting documentation from a medical provider, said Emily Harvey, a Denver-based disability law attorney. Employers are allowed to deny accommodations if they would cause an undue burden to the employer or fundamentally alter the nature or operation of the job or business.
“When it comes to the ADA, and disability rights in general, the analysis is based on the need of the individual,” she said. “Two people with identical diagnoses could need vastly different accommodations to be successful in the same job.”
Mr. Dorfman added that employers are only required to provide an accommodation that is reasonable under the circumstances, whether or not that accommodation meets the preferred request of the employee. For instance, if an immunocompromised physician asked to work from home, but the employer could ensure that all those working around the physician will mask, that could be reasonable enough.
A recent case analysis by Bloomberg Law shows that more courts are siding with employees who request remote work, compared with in past years. Employees who made disability-related remote work requests prevailed in 40% of federal court rulings from 2021 to 2023 versusa success rate of 30% from 2017 to 2019, according to the July 2023 analysis.
The analysis shows that employers still win the majority of the time, but that the gap is closing, Mr. Dorfman said.
In a September 2020 decision, for example, a Massachusetts District Court ruled in favor of an employee with asthma who was precluding from working at home by a behavioral and mental health agency. U.S. Magistrate Judge Katherine Robertson said that the manager was entitled to telework as a reasonable accommodation under the ADA for 60 days or until further notice. The lawsuit was settled in 2021.
“I think judges are much more used to working from home themselves,” Mr. Dorfman said. “That may affect their sense of accepting remote work as a reasonable accommodation. Their personal experience with it [may] actually inform their view of the topic.”
Your accommodation request was denied: Now what?
If you are unsure about your rights under the ADA, a first step is understanding the law’s protections and learning the obligations of your employer.
Keep in mind that not everyone at your workplace may understand the law and what is required, said Dr. Poullos. When making a request to work from home, ensure that you’re using the right words and asking the right people, he advised. Some physicians, for instance, may only discuss the request with their direct supervisor and give up when the request is denied. “The employee might say, ‘I’ve been dealing with some medical issues and I’m really tired and need to adjust my schedule.’ They don’t mention the word ‘disability,’ they don’t mention the ADA, they don’t mention the word ‘accommodation,’ and so that might not trigger the appropriate response.”
Lisa Meeks, PhD, an expert and researcher in disabilities in medical education, encourages physicians and others to follow the appeals process at their institution if they feel their accommodation request has been unjustly denied.
Research shows that physicians who make accommodation requests rarely escalate denials to an appeal, grievance, or complaint, said Dr. Meeks, cohost of the Docs With Disabilities podcast and director of the Docs With Disabilities Initiative. The initiative aims to use research, education, and stories to drive change in perceptions, disability policy, and procedures in health professions and in biomedical and science education.
If an accommodation cannot be agreed on, doctors can reach out the Equal Employment Opportunity Commission and file a discrimination charge. The agency will review the case and provide an opinion on whether the charge has merit. The EEOC’s decision is not binding in court, and even if the agency believes the charge has no merit, employees still have the right to sue, he said.
Ms. Harvey added that the EEOC has many resources on its website, and that most states also have civil rights agencies that have additional resources. Every state and U.S. territory also has a protection and advocacy organization that may be able to help. Physicians can also review their state bar to locate and consult with disability rights attorneys.
Although it may seem like an uphill battle to push for an accommodation, it can be worth it in the end, said Michael Argenyi, MD, an addiction medicine specialist and assistant professor at the University of Massachusetts, Worcester. Dr. Argenyi, who has hearing loss, was featured on the Docs With Disabilities podcast.
“It’s difficult to ‘rock the boat’ and ask for support from the C-suite for employees with disabilities, or to rearrange a small medical office budget to establish a byline just for accommodations,” Dr. Argenyi said. “Yet, the payoff is worthwhile – patients and fellow colleagues notice commitments to diversity building and inclusion.”
A version of this article appeared on Medscape.com.
A radiologist who claims he was forced to resign after requesting to work from home has settled his discrimination lawsuit with a New York hospital.
Although the case was resolved without a definitive win, legal analysts say the complaint raises important questions about whether some physicians have the right to work from home.
Since the pandemic, employers across the country have become more accepting of professionals working remotely.
Richard Heiden, MD, sued New York City Health and Hospitals in 2020, claiming discrimination and retaliation violations under the American with Disabilities Act (ADA) and the New York State Human Rights Law. Dr. Heiden, who has ulcerative colitis, had asked to work off-site during the start of the pandemic, but the hospital denied his accommodation request. Shortly later, administrators accused Dr. Heiden of poor performance and requested he resign or administrators would terminate him, according to his lawsuit.
Attorneys for New York City Health and Hospitals contended that Dr. Heiden was a poorly performing radiologist who was undergoing a performance review at the time of his accommodation request. The radiologist’s departure was related to the results of the review and had nothing to do with his disability or accommodation request, according to the hospital.
The undisclosed settlement ends a 3-year court battle between Dr. Heiden and the hospital corporation.
In an email, Laura Williams, an attorney for the hospital corporation, said that “the settlement was in the best interest of all parties.”
Dr. Heiden and his attorneys also did not respond to requests for comment.
A critical piece to the puzzle is understanding who is protected under the ADA and is therefore entitled to reasonable accommodations, said Doron Dorfman, JSD, an associate professor at Seton Hall University Law School in Newark, N.J., who focuses on disability law.
A common misconception is that only physicians with a physical disability are “disabled,” he said. However, under the law, a disabled individual is anyone with a physical or mental impairment – including mental illness – that limits major life activities; a person with a history of such impairment; or a person who is perceived by others as having an impairment.
“The law is much broader than many people think,” he said. “I think a lot of people don’t think about those with invisible disabilities, such as people with allergies, those who are immunocompromised, those with chronic illnesses. A lot of people don’t see themselves as disabled, and a lot of employers don’t see them as disabled.”
Working from home has not historically been considered a “reasonable accommodation” under the ADA, Mr. Dorfman said. However, that appears to be changing.
“There has been a sea change,” Mr. Dorfman said. “The question is coming before the courts more frequently, and recent legal decisions show judges may be altering their views on the subject.”
What led to the doctor’s lawsuit?
Dr. Heiden, a longtime radiologist, had practiced at Lincoln Medical and Mental Health Center for about a year when he requested to work remotely. (Lincoln is operated by New York City Health and Hospitals.) At the time, the governor of New York had ordered a statewide lockdown because of COVID-19, and Dr. Heiden expressed concern that his ulcerative colitis made him a high-risk individual for the virus, according to court documents.
In his March 22, 2020, request, Dr. Heiden said that, except for fluoroscopy, his job could be done entirely from his home, according to a district court summary of the case. He also offered to pay for any costs associated with the remote work setup.
Around the same time, New York City Health and Hospitals permitted its facilities to issue a limited number of workstations to radiologists to facilitate remote work in the event of COVID-related staffing shortages. Administrators were in the process of acquiring remote radiology workstations and determining which radiologists at Lincoln would receive them, according to the case summary.
On March 24, the chair of radiology at Lincoln met with Dr. Heiden to review the results of a recent focused professional practice evaluation (FPPE). An FPPE refers to an intensive review of an expansive selection of patient cases handled by the subject physician. During the meeting, the chair that claimed Dr. Heiden was a poor performer and was accurate in his assessments 93.8% of the time, which was below the hospital’s 97% threshold, according to Dr. Heiden’s lawsuit. Dr. Heiden disagreed with the results, and the two engaged in several more meetings.
Meanwhile, Dr. Heiden’s accommodation request was forwarded to other administrators. In an email introduced into court evidence, the chair indicated he did not support the accommodation, writing that Dr. Heiden’s “skill set does not meet the criteria for the initial installations” of the workstations.
On March 26, 2020, the chair allegedly asked Dr. Heiden to either resign or he would be terminated and reported to the New York State Office of Professional Medical Conduct. Four days later, Dr. Heiden learned that his accommodation request had been denied. He resigned on April 2, 2020.
In his lawsuit, Dr. Heiden claimed that the hospital discriminated against him on the basis of his disability in violation of ADA by denying him equal terms and conditions of employment and failing to provide a reasonable accommodation.
The defendants, who included the radiology chair, did not dispute that Dr. Heiden was asked to resign or that administrators warned termination, but they argued the impetus was his FPPE results and a history of inaccurate interpretations. Other clinicians and physicians had expressed concerns about Dr. Heiden’s “lack of clarity [and] interpretive errors,” according to deposition testimony. The hospital emphasized the FPPE had concluded before Dr. Heiden’s accommodation request was made.
New York City Health and Hospitals requested a federal judge dismiss the lawsuit for lack of valid claims. In January 2023, U.S. District Judge Lewis Liman allowed the case to proceed, ruling that some of Dr. Heiden’s claims had merit.
“Plaintiff has satisfied his obligation to proffer sufficient evidence to create an inference of retaliatory or discriminatory intent,” Judge Liman wrote in his decision. “[The chair] had not always planned to ask for plaintiff’s resignation based on the results of the FPPE completed on March 10, 2020. The decision to ask for that resignation arose shortly after the request for the accommodation. And there is evidence from which the jury could find that [the chair] was not receptive to making the accommodation.”
A jury trial was scheduled for July 2023, but the parties reached a settlement on May 31, 2023.
Is working from home reasonable for physicians?
The widespread swing to remote work in recent years has paved a smoother road for physicians who request the accommodation, said Peter Poullos, MD, clinical associate professor of radiology, gastroenterology, and hepatology at Stanford (Calif.) University and founder and cochair of the Stanford Medicine Alliance for Disability Inclusion and Equity.
“There is now a precedent and examples all over that working from home for some is a viable alternative to working in the hospital or a clinic,” Dr. Poullos said. “If a lawyer can point to instances of other people having received the same accommodation, even if the accommodation was given to someone without a disability, it’s much harder for an employer to say: ‘It’s not possible.’ Because clearly, it is.”
A key factor is the employee’s job duties and whether the employee can complete them remotely, said Mr. Dorfman. With physicians, the reasonableness would heavily depend on their specialty.
A radiologist, for example, would probably have a stronger case for performing their duties remotely compared with a surgeon, Dr. Poullos said.
In general, whether an accommodation is reasonable is decided on a case-by-case basis and usually includes reviewing supporting documentation from a medical provider, said Emily Harvey, a Denver-based disability law attorney. Employers are allowed to deny accommodations if they would cause an undue burden to the employer or fundamentally alter the nature or operation of the job or business.
“When it comes to the ADA, and disability rights in general, the analysis is based on the need of the individual,” she said. “Two people with identical diagnoses could need vastly different accommodations to be successful in the same job.”
Mr. Dorfman added that employers are only required to provide an accommodation that is reasonable under the circumstances, whether or not that accommodation meets the preferred request of the employee. For instance, if an immunocompromised physician asked to work from home, but the employer could ensure that all those working around the physician will mask, that could be reasonable enough.
A recent case analysis by Bloomberg Law shows that more courts are siding with employees who request remote work, compared with in past years. Employees who made disability-related remote work requests prevailed in 40% of federal court rulings from 2021 to 2023 versusa success rate of 30% from 2017 to 2019, according to the July 2023 analysis.
The analysis shows that employers still win the majority of the time, but that the gap is closing, Mr. Dorfman said.
In a September 2020 decision, for example, a Massachusetts District Court ruled in favor of an employee with asthma who was precluding from working at home by a behavioral and mental health agency. U.S. Magistrate Judge Katherine Robertson said that the manager was entitled to telework as a reasonable accommodation under the ADA for 60 days or until further notice. The lawsuit was settled in 2021.
“I think judges are much more used to working from home themselves,” Mr. Dorfman said. “That may affect their sense of accepting remote work as a reasonable accommodation. Their personal experience with it [may] actually inform their view of the topic.”
Your accommodation request was denied: Now what?
If you are unsure about your rights under the ADA, a first step is understanding the law’s protections and learning the obligations of your employer.
Keep in mind that not everyone at your workplace may understand the law and what is required, said Dr. Poullos. When making a request to work from home, ensure that you’re using the right words and asking the right people, he advised. Some physicians, for instance, may only discuss the request with their direct supervisor and give up when the request is denied. “The employee might say, ‘I’ve been dealing with some medical issues and I’m really tired and need to adjust my schedule.’ They don’t mention the word ‘disability,’ they don’t mention the ADA, they don’t mention the word ‘accommodation,’ and so that might not trigger the appropriate response.”
Lisa Meeks, PhD, an expert and researcher in disabilities in medical education, encourages physicians and others to follow the appeals process at their institution if they feel their accommodation request has been unjustly denied.
Research shows that physicians who make accommodation requests rarely escalate denials to an appeal, grievance, or complaint, said Dr. Meeks, cohost of the Docs With Disabilities podcast and director of the Docs With Disabilities Initiative. The initiative aims to use research, education, and stories to drive change in perceptions, disability policy, and procedures in health professions and in biomedical and science education.
If an accommodation cannot be agreed on, doctors can reach out the Equal Employment Opportunity Commission and file a discrimination charge. The agency will review the case and provide an opinion on whether the charge has merit. The EEOC’s decision is not binding in court, and even if the agency believes the charge has no merit, employees still have the right to sue, he said.
Ms. Harvey added that the EEOC has many resources on its website, and that most states also have civil rights agencies that have additional resources. Every state and U.S. territory also has a protection and advocacy organization that may be able to help. Physicians can also review their state bar to locate and consult with disability rights attorneys.
Although it may seem like an uphill battle to push for an accommodation, it can be worth it in the end, said Michael Argenyi, MD, an addiction medicine specialist and assistant professor at the University of Massachusetts, Worcester. Dr. Argenyi, who has hearing loss, was featured on the Docs With Disabilities podcast.
“It’s difficult to ‘rock the boat’ and ask for support from the C-suite for employees with disabilities, or to rearrange a small medical office budget to establish a byline just for accommodations,” Dr. Argenyi said. “Yet, the payoff is worthwhile – patients and fellow colleagues notice commitments to diversity building and inclusion.”
A version of this article appeared on Medscape.com.
A radiologist who claims he was forced to resign after requesting to work from home has settled his discrimination lawsuit with a New York hospital.
Although the case was resolved without a definitive win, legal analysts say the complaint raises important questions about whether some physicians have the right to work from home.
Since the pandemic, employers across the country have become more accepting of professionals working remotely.
Richard Heiden, MD, sued New York City Health and Hospitals in 2020, claiming discrimination and retaliation violations under the American with Disabilities Act (ADA) and the New York State Human Rights Law. Dr. Heiden, who has ulcerative colitis, had asked to work off-site during the start of the pandemic, but the hospital denied his accommodation request. Shortly later, administrators accused Dr. Heiden of poor performance and requested he resign or administrators would terminate him, according to his lawsuit.
Attorneys for New York City Health and Hospitals contended that Dr. Heiden was a poorly performing radiologist who was undergoing a performance review at the time of his accommodation request. The radiologist’s departure was related to the results of the review and had nothing to do with his disability or accommodation request, according to the hospital.
The undisclosed settlement ends a 3-year court battle between Dr. Heiden and the hospital corporation.
In an email, Laura Williams, an attorney for the hospital corporation, said that “the settlement was in the best interest of all parties.”
Dr. Heiden and his attorneys also did not respond to requests for comment.
A critical piece to the puzzle is understanding who is protected under the ADA and is therefore entitled to reasonable accommodations, said Doron Dorfman, JSD, an associate professor at Seton Hall University Law School in Newark, N.J., who focuses on disability law.
A common misconception is that only physicians with a physical disability are “disabled,” he said. However, under the law, a disabled individual is anyone with a physical or mental impairment – including mental illness – that limits major life activities; a person with a history of such impairment; or a person who is perceived by others as having an impairment.
“The law is much broader than many people think,” he said. “I think a lot of people don’t think about those with invisible disabilities, such as people with allergies, those who are immunocompromised, those with chronic illnesses. A lot of people don’t see themselves as disabled, and a lot of employers don’t see them as disabled.”
Working from home has not historically been considered a “reasonable accommodation” under the ADA, Mr. Dorfman said. However, that appears to be changing.
“There has been a sea change,” Mr. Dorfman said. “The question is coming before the courts more frequently, and recent legal decisions show judges may be altering their views on the subject.”
What led to the doctor’s lawsuit?
Dr. Heiden, a longtime radiologist, had practiced at Lincoln Medical and Mental Health Center for about a year when he requested to work remotely. (Lincoln is operated by New York City Health and Hospitals.) At the time, the governor of New York had ordered a statewide lockdown because of COVID-19, and Dr. Heiden expressed concern that his ulcerative colitis made him a high-risk individual for the virus, according to court documents.
In his March 22, 2020, request, Dr. Heiden said that, except for fluoroscopy, his job could be done entirely from his home, according to a district court summary of the case. He also offered to pay for any costs associated with the remote work setup.
Around the same time, New York City Health and Hospitals permitted its facilities to issue a limited number of workstations to radiologists to facilitate remote work in the event of COVID-related staffing shortages. Administrators were in the process of acquiring remote radiology workstations and determining which radiologists at Lincoln would receive them, according to the case summary.
On March 24, the chair of radiology at Lincoln met with Dr. Heiden to review the results of a recent focused professional practice evaluation (FPPE). An FPPE refers to an intensive review of an expansive selection of patient cases handled by the subject physician. During the meeting, the chair that claimed Dr. Heiden was a poor performer and was accurate in his assessments 93.8% of the time, which was below the hospital’s 97% threshold, according to Dr. Heiden’s lawsuit. Dr. Heiden disagreed with the results, and the two engaged in several more meetings.
Meanwhile, Dr. Heiden’s accommodation request was forwarded to other administrators. In an email introduced into court evidence, the chair indicated he did not support the accommodation, writing that Dr. Heiden’s “skill set does not meet the criteria for the initial installations” of the workstations.
On March 26, 2020, the chair allegedly asked Dr. Heiden to either resign or he would be terminated and reported to the New York State Office of Professional Medical Conduct. Four days later, Dr. Heiden learned that his accommodation request had been denied. He resigned on April 2, 2020.
In his lawsuit, Dr. Heiden claimed that the hospital discriminated against him on the basis of his disability in violation of ADA by denying him equal terms and conditions of employment and failing to provide a reasonable accommodation.
The defendants, who included the radiology chair, did not dispute that Dr. Heiden was asked to resign or that administrators warned termination, but they argued the impetus was his FPPE results and a history of inaccurate interpretations. Other clinicians and physicians had expressed concerns about Dr. Heiden’s “lack of clarity [and] interpretive errors,” according to deposition testimony. The hospital emphasized the FPPE had concluded before Dr. Heiden’s accommodation request was made.
New York City Health and Hospitals requested a federal judge dismiss the lawsuit for lack of valid claims. In January 2023, U.S. District Judge Lewis Liman allowed the case to proceed, ruling that some of Dr. Heiden’s claims had merit.
“Plaintiff has satisfied his obligation to proffer sufficient evidence to create an inference of retaliatory or discriminatory intent,” Judge Liman wrote in his decision. “[The chair] had not always planned to ask for plaintiff’s resignation based on the results of the FPPE completed on March 10, 2020. The decision to ask for that resignation arose shortly after the request for the accommodation. And there is evidence from which the jury could find that [the chair] was not receptive to making the accommodation.”
A jury trial was scheduled for July 2023, but the parties reached a settlement on May 31, 2023.
Is working from home reasonable for physicians?
The widespread swing to remote work in recent years has paved a smoother road for physicians who request the accommodation, said Peter Poullos, MD, clinical associate professor of radiology, gastroenterology, and hepatology at Stanford (Calif.) University and founder and cochair of the Stanford Medicine Alliance for Disability Inclusion and Equity.
“There is now a precedent and examples all over that working from home for some is a viable alternative to working in the hospital or a clinic,” Dr. Poullos said. “If a lawyer can point to instances of other people having received the same accommodation, even if the accommodation was given to someone without a disability, it’s much harder for an employer to say: ‘It’s not possible.’ Because clearly, it is.”
A key factor is the employee’s job duties and whether the employee can complete them remotely, said Mr. Dorfman. With physicians, the reasonableness would heavily depend on their specialty.
A radiologist, for example, would probably have a stronger case for performing their duties remotely compared with a surgeon, Dr. Poullos said.
In general, whether an accommodation is reasonable is decided on a case-by-case basis and usually includes reviewing supporting documentation from a medical provider, said Emily Harvey, a Denver-based disability law attorney. Employers are allowed to deny accommodations if they would cause an undue burden to the employer or fundamentally alter the nature or operation of the job or business.
“When it comes to the ADA, and disability rights in general, the analysis is based on the need of the individual,” she said. “Two people with identical diagnoses could need vastly different accommodations to be successful in the same job.”
Mr. Dorfman added that employers are only required to provide an accommodation that is reasonable under the circumstances, whether or not that accommodation meets the preferred request of the employee. For instance, if an immunocompromised physician asked to work from home, but the employer could ensure that all those working around the physician will mask, that could be reasonable enough.
A recent case analysis by Bloomberg Law shows that more courts are siding with employees who request remote work, compared with in past years. Employees who made disability-related remote work requests prevailed in 40% of federal court rulings from 2021 to 2023 versusa success rate of 30% from 2017 to 2019, according to the July 2023 analysis.
The analysis shows that employers still win the majority of the time, but that the gap is closing, Mr. Dorfman said.
In a September 2020 decision, for example, a Massachusetts District Court ruled in favor of an employee with asthma who was precluding from working at home by a behavioral and mental health agency. U.S. Magistrate Judge Katherine Robertson said that the manager was entitled to telework as a reasonable accommodation under the ADA for 60 days or until further notice. The lawsuit was settled in 2021.
“I think judges are much more used to working from home themselves,” Mr. Dorfman said. “That may affect their sense of accepting remote work as a reasonable accommodation. Their personal experience with it [may] actually inform their view of the topic.”
Your accommodation request was denied: Now what?
If you are unsure about your rights under the ADA, a first step is understanding the law’s protections and learning the obligations of your employer.
Keep in mind that not everyone at your workplace may understand the law and what is required, said Dr. Poullos. When making a request to work from home, ensure that you’re using the right words and asking the right people, he advised. Some physicians, for instance, may only discuss the request with their direct supervisor and give up when the request is denied. “The employee might say, ‘I’ve been dealing with some medical issues and I’m really tired and need to adjust my schedule.’ They don’t mention the word ‘disability,’ they don’t mention the ADA, they don’t mention the word ‘accommodation,’ and so that might not trigger the appropriate response.”
Lisa Meeks, PhD, an expert and researcher in disabilities in medical education, encourages physicians and others to follow the appeals process at their institution if they feel their accommodation request has been unjustly denied.
Research shows that physicians who make accommodation requests rarely escalate denials to an appeal, grievance, or complaint, said Dr. Meeks, cohost of the Docs With Disabilities podcast and director of the Docs With Disabilities Initiative. The initiative aims to use research, education, and stories to drive change in perceptions, disability policy, and procedures in health professions and in biomedical and science education.
If an accommodation cannot be agreed on, doctors can reach out the Equal Employment Opportunity Commission and file a discrimination charge. The agency will review the case and provide an opinion on whether the charge has merit. The EEOC’s decision is not binding in court, and even if the agency believes the charge has no merit, employees still have the right to sue, he said.
Ms. Harvey added that the EEOC has many resources on its website, and that most states also have civil rights agencies that have additional resources. Every state and U.S. territory also has a protection and advocacy organization that may be able to help. Physicians can also review their state bar to locate and consult with disability rights attorneys.
Although it may seem like an uphill battle to push for an accommodation, it can be worth it in the end, said Michael Argenyi, MD, an addiction medicine specialist and assistant professor at the University of Massachusetts, Worcester. Dr. Argenyi, who has hearing loss, was featured on the Docs With Disabilities podcast.
“It’s difficult to ‘rock the boat’ and ask for support from the C-suite for employees with disabilities, or to rearrange a small medical office budget to establish a byline just for accommodations,” Dr. Argenyi said. “Yet, the payoff is worthwhile – patients and fellow colleagues notice commitments to diversity building and inclusion.”
A version of this article appeared on Medscape.com.
The top tax breaks that physicians use
Plenty of perks come along with earning a physician’s salary, but a low tax rate isn’t among them. Medscape’s Physicians and Taxes Report 2023 shows that last year, doctors paid an average of nearly $100,000 in state and federal taxes, and three-quarters of them thought that they were paying too much to Uncle Sam. In most cases, it’s impossible to eliminate that tax bill, but physicians told us they have found ways to minimize it.
“The percentage you have to pay in taxes escalates as you earn more money, and most doctors are at the maximum rate,” says Paul Joseph, a certified public accountant and founder of Joseph & Joseph Tax & Payroll in Williamston, Mich. “So every dollar you can deduct from your income is worth more.”
To claim most of these options, you’ll need to itemize your deductions when filing your taxes.
Contribute to charity
Claimed by 70% of physicians in 2022.
Who’s eligible: Anyone.
How it works: If you itemize your taxes, you can deduct the value of cash, securities, or property donations to 501(c)(3) organizations. You’ll need a receipt from the charity and a third-party appraisal for any property donations worth more than $5,000.
Pro tip: Donating stocks that have appreciated in value can deliver additional tax benefits: You get to write off both the value of the contribution and avoid capital gains taxes that you’d face for selling the security.
Contribute to a pre-tax 401(k) account
Claimed by 60% of physicians in 2022.
Who’s eligible: Those who work for a company that sponsors a 401(k) plan.
How it works: Contributions to a 401(k) or 403(b) account come directly out of your paycheck, pre-tax, and grow tax-free until you withdraw them in retirement. Many companies offer a match on contributions. In 2023, you can contribute up to $22,500 ($30,000 if you’re age 50 or older) to a 401(k) account.
Pro tip: If you’re maxing out your 401(k) account, you can stash money in other tax-advantaged accounts such as a health savings account (if you have a high-deductible health plan) or an individual retirement account (IRA). Although employees with access to a 401(k) may not get the pre-tax advantage of the IRA contributions, the money will grow tax-free through retirement, and you may have access to additional investment options unavailable in your workplace plan.
“You want to maximize your retirement contributions,” says Mark Steber, the chief tax information officer for Jackson Hewitt Tax Services. “If you’re not taking full advantage of them, you’re probably leaving some tax dollars on the table.”
If you’re self-employed and don’t have access to a workplace plan, there are several options for tax-advantaged retirement savings, including a SEP IRA and a solo 401(k).
Deduct interest on a home mortgage
Claimed by 52% of physicians.
Who’s eligible: Most homeowners who have a mortgage.
How it works: Homeowners can deduct the interest paid on the first $750,000 of their mortgage. (Those who have had the same mortgage since before December 16, 2007, can deduct interest on the first $1 million of their loan.)
Pro tip: If you purchased a home this year and bought points to reduce the rate, you may be able to deduct the cost of those points on your taxes.
Physicians might also be eligible for other home-related tax benefits, such as for green home improvements under the Inflation Reduction Act or for home equity loans used to improve the value of your home.
Write off eligible business expenses
Claimed by 46% of physicians.
Who’s eligible: Physicians who own all or a portion of their practice, as well as those who work as consultants or contractors paid with a 1099.
How it works: Doctors who run their business using an LLC or S corporation can itemize the deductions on their Schedule C. There are dozens of deductions that might qualify, including for office space and supplies, medical equipment, uniforms, staff wages and benefits, and state and local tax payments. Physicians who work as consultants can deduct home office expenses, travel costs, and the price of supplies purchased for the job.
“For business expenses, you want to make sure that you’re tracking those expenses on an ongoing basis, rather than trying to reconstruct something at the end of the year from 8 months ago,” Mr. Joseph says. “You want to have a system in place that’s calculating those expenses every single day.”
Pro tip: The Tax Cuts and Jobs Act of 2017 also allows owners of pass-through businesses to deduct up to 20% of their business income.
“Not all physicians will qualify for that, because they are in a service-based business and many of them make too much money, but it’s always a good idea to look at whether that’s something they’re eligible for and make sure that they claim it,” says Eric Bronnenkant, head of tax at New York–based investment company Betterment.
Contribute to a 529 college savings plan
Claimed by 27% of physicians.
Who’s eligible: Those who live in the 37 states that offer a credit or deduction for 529 plan contributions.
How it works: The rules and amounts that qualify vary significantly by state. Most states offer benefits for contributions to in-state accounts only, whereas others offer a tax break for contributions to any 529 account.
Although there is no federal income tax benefit for contributions to a 529 plan, the money grows tax-free until tapped for qualified education expenses, which include both private primary and high school tuition and college costs. Starting in 2024, up to $35,000 in unused funds can roll over into a Roth IRA for the beneficiary.
“It’s not just about the immediate deduction with a 529 account,” says Brian Copeland, partner and director of financial planning with Hightower Wealth Advisors in St. Louis. “It’s not saving you a lot on day one; it’s more about as that account grows, you don’t have to pay taxes on it along the way, so you’re sheltering it from taxes for the 18 years you’re saving for your kids’ college.”
Pro tip: Even if you live in a state without a state income tax or without a tax break for 529 contributions, opening an account can be a smart financial move. Because you don’t need to choose an in-state plan for the tax breaks, look for one that offers low fees and investment options that you like.
Sell investments at a loss
Claimed by 22% of physicians.
Who’s eligible: Anyone who has sold stocks, mutual funds, or other investments at a loss.
How it works: After selling a security that has lost value, you can deduct the value of that loss on your taxes to offset capital gains in the same year. If you have more losses than gains, you can use the losses to offset up to $3,000 in ordinary income per year. If you have more than $3,000 in losses, you can carry those losses forward to offset future income or capital gains.
Pro tip: In years with a lot of market volatility, such as this one, there’s potential to engage in “tax loss harvesting” in which you intentionally sell securities that have lost value to realize the losses for the tax benefits. Keep in mind that if you sell a security at a loss, you cannot repurchase the same security within 30 days – the IRS sees that as a “wash sale,” which does not qualify for a capital loss for tax purposes.
Contribute to a backdoor Roth IRA
Claimed by 20% of physicians.
Who’s eligible: Anyone who wishes to contribute to a Roth IRA but is not allowed to do so because their income is too high.
How it works: High earners typically don’t qualify for contributions to a Roth IRA, in which contributions go in after taxes but grow tax-free and distributions in retirement are also tax-free. But there are no income requirements for making after-tax contributions to a traditional and then converting it to a Roth IRA.
There are, however, complex tax rules for those who also have a traditional IRA that’s funded with pre-tax dollars. If that’s the case, work with a tax pro or financial advisor to determine whether a backdoor Roth conversion is the most tax-efficient approach for your situation.
Pro tip: A growing number of workplace retirement plans now include an option for Roth contributions. There are no income limits on a Roth 401(k), so contributing to that type of an account could be a smart route for taxpayers for whom a backdoor conversion doesn’t make sense.
A version of this article appeared on Medscape.com.
Plenty of perks come along with earning a physician’s salary, but a low tax rate isn’t among them. Medscape’s Physicians and Taxes Report 2023 shows that last year, doctors paid an average of nearly $100,000 in state and federal taxes, and three-quarters of them thought that they were paying too much to Uncle Sam. In most cases, it’s impossible to eliminate that tax bill, but physicians told us they have found ways to minimize it.
“The percentage you have to pay in taxes escalates as you earn more money, and most doctors are at the maximum rate,” says Paul Joseph, a certified public accountant and founder of Joseph & Joseph Tax & Payroll in Williamston, Mich. “So every dollar you can deduct from your income is worth more.”
To claim most of these options, you’ll need to itemize your deductions when filing your taxes.
Contribute to charity
Claimed by 70% of physicians in 2022.
Who’s eligible: Anyone.
How it works: If you itemize your taxes, you can deduct the value of cash, securities, or property donations to 501(c)(3) organizations. You’ll need a receipt from the charity and a third-party appraisal for any property donations worth more than $5,000.
Pro tip: Donating stocks that have appreciated in value can deliver additional tax benefits: You get to write off both the value of the contribution and avoid capital gains taxes that you’d face for selling the security.
Contribute to a pre-tax 401(k) account
Claimed by 60% of physicians in 2022.
Who’s eligible: Those who work for a company that sponsors a 401(k) plan.
How it works: Contributions to a 401(k) or 403(b) account come directly out of your paycheck, pre-tax, and grow tax-free until you withdraw them in retirement. Many companies offer a match on contributions. In 2023, you can contribute up to $22,500 ($30,000 if you’re age 50 or older) to a 401(k) account.
Pro tip: If you’re maxing out your 401(k) account, you can stash money in other tax-advantaged accounts such as a health savings account (if you have a high-deductible health plan) or an individual retirement account (IRA). Although employees with access to a 401(k) may not get the pre-tax advantage of the IRA contributions, the money will grow tax-free through retirement, and you may have access to additional investment options unavailable in your workplace plan.
“You want to maximize your retirement contributions,” says Mark Steber, the chief tax information officer for Jackson Hewitt Tax Services. “If you’re not taking full advantage of them, you’re probably leaving some tax dollars on the table.”
If you’re self-employed and don’t have access to a workplace plan, there are several options for tax-advantaged retirement savings, including a SEP IRA and a solo 401(k).
Deduct interest on a home mortgage
Claimed by 52% of physicians.
Who’s eligible: Most homeowners who have a mortgage.
How it works: Homeowners can deduct the interest paid on the first $750,000 of their mortgage. (Those who have had the same mortgage since before December 16, 2007, can deduct interest on the first $1 million of their loan.)
Pro tip: If you purchased a home this year and bought points to reduce the rate, you may be able to deduct the cost of those points on your taxes.
Physicians might also be eligible for other home-related tax benefits, such as for green home improvements under the Inflation Reduction Act or for home equity loans used to improve the value of your home.
Write off eligible business expenses
Claimed by 46% of physicians.
Who’s eligible: Physicians who own all or a portion of their practice, as well as those who work as consultants or contractors paid with a 1099.
How it works: Doctors who run their business using an LLC or S corporation can itemize the deductions on their Schedule C. There are dozens of deductions that might qualify, including for office space and supplies, medical equipment, uniforms, staff wages and benefits, and state and local tax payments. Physicians who work as consultants can deduct home office expenses, travel costs, and the price of supplies purchased for the job.
“For business expenses, you want to make sure that you’re tracking those expenses on an ongoing basis, rather than trying to reconstruct something at the end of the year from 8 months ago,” Mr. Joseph says. “You want to have a system in place that’s calculating those expenses every single day.”
Pro tip: The Tax Cuts and Jobs Act of 2017 also allows owners of pass-through businesses to deduct up to 20% of their business income.
“Not all physicians will qualify for that, because they are in a service-based business and many of them make too much money, but it’s always a good idea to look at whether that’s something they’re eligible for and make sure that they claim it,” says Eric Bronnenkant, head of tax at New York–based investment company Betterment.
Contribute to a 529 college savings plan
Claimed by 27% of physicians.
Who’s eligible: Those who live in the 37 states that offer a credit or deduction for 529 plan contributions.
How it works: The rules and amounts that qualify vary significantly by state. Most states offer benefits for contributions to in-state accounts only, whereas others offer a tax break for contributions to any 529 account.
Although there is no federal income tax benefit for contributions to a 529 plan, the money grows tax-free until tapped for qualified education expenses, which include both private primary and high school tuition and college costs. Starting in 2024, up to $35,000 in unused funds can roll over into a Roth IRA for the beneficiary.
“It’s not just about the immediate deduction with a 529 account,” says Brian Copeland, partner and director of financial planning with Hightower Wealth Advisors in St. Louis. “It’s not saving you a lot on day one; it’s more about as that account grows, you don’t have to pay taxes on it along the way, so you’re sheltering it from taxes for the 18 years you’re saving for your kids’ college.”
Pro tip: Even if you live in a state without a state income tax or without a tax break for 529 contributions, opening an account can be a smart financial move. Because you don’t need to choose an in-state plan for the tax breaks, look for one that offers low fees and investment options that you like.
Sell investments at a loss
Claimed by 22% of physicians.
Who’s eligible: Anyone who has sold stocks, mutual funds, or other investments at a loss.
How it works: After selling a security that has lost value, you can deduct the value of that loss on your taxes to offset capital gains in the same year. If you have more losses than gains, you can use the losses to offset up to $3,000 in ordinary income per year. If you have more than $3,000 in losses, you can carry those losses forward to offset future income or capital gains.
Pro tip: In years with a lot of market volatility, such as this one, there’s potential to engage in “tax loss harvesting” in which you intentionally sell securities that have lost value to realize the losses for the tax benefits. Keep in mind that if you sell a security at a loss, you cannot repurchase the same security within 30 days – the IRS sees that as a “wash sale,” which does not qualify for a capital loss for tax purposes.
Contribute to a backdoor Roth IRA
Claimed by 20% of physicians.
Who’s eligible: Anyone who wishes to contribute to a Roth IRA but is not allowed to do so because their income is too high.
How it works: High earners typically don’t qualify for contributions to a Roth IRA, in which contributions go in after taxes but grow tax-free and distributions in retirement are also tax-free. But there are no income requirements for making after-tax contributions to a traditional and then converting it to a Roth IRA.
There are, however, complex tax rules for those who also have a traditional IRA that’s funded with pre-tax dollars. If that’s the case, work with a tax pro or financial advisor to determine whether a backdoor Roth conversion is the most tax-efficient approach for your situation.
Pro tip: A growing number of workplace retirement plans now include an option for Roth contributions. There are no income limits on a Roth 401(k), so contributing to that type of an account could be a smart route for taxpayers for whom a backdoor conversion doesn’t make sense.
A version of this article appeared on Medscape.com.
Plenty of perks come along with earning a physician’s salary, but a low tax rate isn’t among them. Medscape’s Physicians and Taxes Report 2023 shows that last year, doctors paid an average of nearly $100,000 in state and federal taxes, and three-quarters of them thought that they were paying too much to Uncle Sam. In most cases, it’s impossible to eliminate that tax bill, but physicians told us they have found ways to minimize it.
“The percentage you have to pay in taxes escalates as you earn more money, and most doctors are at the maximum rate,” says Paul Joseph, a certified public accountant and founder of Joseph & Joseph Tax & Payroll in Williamston, Mich. “So every dollar you can deduct from your income is worth more.”
To claim most of these options, you’ll need to itemize your deductions when filing your taxes.
Contribute to charity
Claimed by 70% of physicians in 2022.
Who’s eligible: Anyone.
How it works: If you itemize your taxes, you can deduct the value of cash, securities, or property donations to 501(c)(3) organizations. You’ll need a receipt from the charity and a third-party appraisal for any property donations worth more than $5,000.
Pro tip: Donating stocks that have appreciated in value can deliver additional tax benefits: You get to write off both the value of the contribution and avoid capital gains taxes that you’d face for selling the security.
Contribute to a pre-tax 401(k) account
Claimed by 60% of physicians in 2022.
Who’s eligible: Those who work for a company that sponsors a 401(k) plan.
How it works: Contributions to a 401(k) or 403(b) account come directly out of your paycheck, pre-tax, and grow tax-free until you withdraw them in retirement. Many companies offer a match on contributions. In 2023, you can contribute up to $22,500 ($30,000 if you’re age 50 or older) to a 401(k) account.
Pro tip: If you’re maxing out your 401(k) account, you can stash money in other tax-advantaged accounts such as a health savings account (if you have a high-deductible health plan) or an individual retirement account (IRA). Although employees with access to a 401(k) may not get the pre-tax advantage of the IRA contributions, the money will grow tax-free through retirement, and you may have access to additional investment options unavailable in your workplace plan.
“You want to maximize your retirement contributions,” says Mark Steber, the chief tax information officer for Jackson Hewitt Tax Services. “If you’re not taking full advantage of them, you’re probably leaving some tax dollars on the table.”
If you’re self-employed and don’t have access to a workplace plan, there are several options for tax-advantaged retirement savings, including a SEP IRA and a solo 401(k).
Deduct interest on a home mortgage
Claimed by 52% of physicians.
Who’s eligible: Most homeowners who have a mortgage.
How it works: Homeowners can deduct the interest paid on the first $750,000 of their mortgage. (Those who have had the same mortgage since before December 16, 2007, can deduct interest on the first $1 million of their loan.)
Pro tip: If you purchased a home this year and bought points to reduce the rate, you may be able to deduct the cost of those points on your taxes.
Physicians might also be eligible for other home-related tax benefits, such as for green home improvements under the Inflation Reduction Act or for home equity loans used to improve the value of your home.
Write off eligible business expenses
Claimed by 46% of physicians.
Who’s eligible: Physicians who own all or a portion of their practice, as well as those who work as consultants or contractors paid with a 1099.
How it works: Doctors who run their business using an LLC or S corporation can itemize the deductions on their Schedule C. There are dozens of deductions that might qualify, including for office space and supplies, medical equipment, uniforms, staff wages and benefits, and state and local tax payments. Physicians who work as consultants can deduct home office expenses, travel costs, and the price of supplies purchased for the job.
“For business expenses, you want to make sure that you’re tracking those expenses on an ongoing basis, rather than trying to reconstruct something at the end of the year from 8 months ago,” Mr. Joseph says. “You want to have a system in place that’s calculating those expenses every single day.”
Pro tip: The Tax Cuts and Jobs Act of 2017 also allows owners of pass-through businesses to deduct up to 20% of their business income.
“Not all physicians will qualify for that, because they are in a service-based business and many of them make too much money, but it’s always a good idea to look at whether that’s something they’re eligible for and make sure that they claim it,” says Eric Bronnenkant, head of tax at New York–based investment company Betterment.
Contribute to a 529 college savings plan
Claimed by 27% of physicians.
Who’s eligible: Those who live in the 37 states that offer a credit or deduction for 529 plan contributions.
How it works: The rules and amounts that qualify vary significantly by state. Most states offer benefits for contributions to in-state accounts only, whereas others offer a tax break for contributions to any 529 account.
Although there is no federal income tax benefit for contributions to a 529 plan, the money grows tax-free until tapped for qualified education expenses, which include both private primary and high school tuition and college costs. Starting in 2024, up to $35,000 in unused funds can roll over into a Roth IRA for the beneficiary.
“It’s not just about the immediate deduction with a 529 account,” says Brian Copeland, partner and director of financial planning with Hightower Wealth Advisors in St. Louis. “It’s not saving you a lot on day one; it’s more about as that account grows, you don’t have to pay taxes on it along the way, so you’re sheltering it from taxes for the 18 years you’re saving for your kids’ college.”
Pro tip: Even if you live in a state without a state income tax or without a tax break for 529 contributions, opening an account can be a smart financial move. Because you don’t need to choose an in-state plan for the tax breaks, look for one that offers low fees and investment options that you like.
Sell investments at a loss
Claimed by 22% of physicians.
Who’s eligible: Anyone who has sold stocks, mutual funds, or other investments at a loss.
How it works: After selling a security that has lost value, you can deduct the value of that loss on your taxes to offset capital gains in the same year. If you have more losses than gains, you can use the losses to offset up to $3,000 in ordinary income per year. If you have more than $3,000 in losses, you can carry those losses forward to offset future income or capital gains.
Pro tip: In years with a lot of market volatility, such as this one, there’s potential to engage in “tax loss harvesting” in which you intentionally sell securities that have lost value to realize the losses for the tax benefits. Keep in mind that if you sell a security at a loss, you cannot repurchase the same security within 30 days – the IRS sees that as a “wash sale,” which does not qualify for a capital loss for tax purposes.
Contribute to a backdoor Roth IRA
Claimed by 20% of physicians.
Who’s eligible: Anyone who wishes to contribute to a Roth IRA but is not allowed to do so because their income is too high.
How it works: High earners typically don’t qualify for contributions to a Roth IRA, in which contributions go in after taxes but grow tax-free and distributions in retirement are also tax-free. But there are no income requirements for making after-tax contributions to a traditional and then converting it to a Roth IRA.
There are, however, complex tax rules for those who also have a traditional IRA that’s funded with pre-tax dollars. If that’s the case, work with a tax pro or financial advisor to determine whether a backdoor Roth conversion is the most tax-efficient approach for your situation.
Pro tip: A growing number of workplace retirement plans now include an option for Roth contributions. There are no income limits on a Roth 401(k), so contributing to that type of an account could be a smart route for taxpayers for whom a backdoor conversion doesn’t make sense.
A version of this article appeared on Medscape.com.
Many patients with NSCLC receive immunotherapy ‘indefinitely’ – Are they benefiting?
Most patients with non–small cell lung cancer (NSCLC) who are long-term responders to immunotherapy will continue receiving treatment beyond 2 years. However, the best available evidence to date indicates that receiving immunotherapy after this 2-year mark likely offers no survival benefit.
Is it an overabundance of caution? A desire for more definitive data? Or is it simply a judgment call oncologists make on the basis of the individual patient?
Lova Sun, MD, MSCE, of the University of Pennsylvania in Philadelphia, believes the general inconsistency between the data and clinical practice “likely reflects significant hesitation on the part of clinicians, patients, or both to stop a treatment that is still ‘working.’ ”
H. Jack West, MD, agreed, adding that “in an ambiguous situation, a U.S.-based population is going to err on the side of overtreatment.”
Without “incontrovertible evidence” that immunotherapy should stop at 2 years, “many, many, many patients and clinicians are going to favor continuing ‘doing what you’re doing’ in the absence of either prohibitive toxicity or clinically significant disease progression,” said Dr. West of the City of Hope Comprehensive Cancer Center, Duarte, Calif.
One factor adding to this ambiguity: Most pivotal studies that examine first-line immunotherapy in NSCLC limit therapy duration to 2 years.
Another key factor is the absence of prospective data as to when to stop treatment for these patients, according to Martin Reck, MD, PhD, head of thoracic oncology at the Lung Clinic Grosshansdorf (Germany).
“We have never prospectively investigated the correlation of the duration of a checkpoint blockade and the efficacy of treatment,” Dr. Reck said. “And this is a big problem.” It means “we really do not know how long we should treat the patient.”
To make matters muddier, some data do suggest that more therapy may be better. The recent Checkmate 153 trial, for instance, found that patients who had no signs of disease progression and who received 1-year fixed-duration nivolumab had significantly shorter progression-free and overall survival than those who received treatment indefinitely.
However, randomized trials with longer-term follow-up suggest durable responses can be maintained for years after immunotherapy is stopped.
Data from the KEYNOTE-024 trial, for instance, showed that more than 45% of patients with metastatic NSCLC and high tumor PD-L1 expression who received pembrolizumab for 2 years remained alive at 5 years without further treatment or disease progression. Another trial, KEYNOTE-407, demonstrated similar 5-year survival outcomes among patients with advanced squamous NSCLC, regardless of PD-L1 status, who completed 2 years of chemotherapy plus pembrolizumab followed by maintenance pembrolizumab.
With these studies, however, “we can only speculate about whether the proportion of patients alive without progression would be substantially higher if treatment with immunotherapy continued longer,” Dr. West wrote in a recent editorial .
Perhaps the most telling data so far come from a recent retrospective analysis from Dr. Sun and colleagues. The researchers directly compared survival outcomes among patients who continued receiving immunotherapy indefinitely with outcomes among patients for whom immunotherapy was discontinued at 2 years.
The JAMA Oncology study, which focused on 706 patients with NSCLC who completed 2 years of therapy, found that only 16% stopped receiving immune checkpoint inhibitor therapy at 2 years, whereas the remaining 84% continued receiving treatment indefinitely.
Among patients who continued receiving immunotherapy for 2 additional years, overall survival was not better than among those who stopped receiving immunotherapy at the 2-year mark. Even among the 11 patients whose condition progressed when therapy was discontinued, most still did well after treatment was resumed.
However, the retrospective design of the study limits its impact.
Without more definitive “data about when the treatment can be stopped,” many continue “indefinitely as long as the patient is tolerating treatment and the disease is not progressing,” Conor E. Steuer, MD, and Suresh S. Ramalingam, MD, of Winship Cancer Institute at Emory University, Atlanta, wrote in a recent review.
Impact on practice?
Dr. Sun views her team’s findings not as a recommendation to halt immunotherapy for every patient at 2 years but rather as “one piece of data that may provide reassurance to providers and patients who wish to stop at 2 years.”
Ultimately, however, the decision as to when or whether to stop immunotherapy for long-term responders is “an individualized one that requires shared decision-making and consideration of each patient’s clinical history, preferences, and risk tolerance,” Dr. Sun explained.
Dr. Reck agreed, noting that until prospective trials evaluate a fixed approach, the duration of immunotherapy “has to be determined by the treating physician and the individual patient.”
For a patient with metastatic NSCLC who is having an excellent response to checkpoint blockade, “we are somewhat afraid to stop the immunotherapy,” explained Dr. Reck, “because we are afraid the disease might relapse.” However, he noted, for patients who have a stable response to therapy, it may make sense to consider discontinuing checkpoint blockade.
Outside of survival outcomes, oncologists should also consider quality of life. Stopping treatment at 2 years comes with a “lower risk of toxic effects, less time in treatment for patients, and considerably lower costs for our health care system,” said Dr. West.
But for a fixed strategy to become more standard practice, the burden of proof is high, Dr. West said.
Jonathan W. Goldman, MD, says he understands the mentality, “If it’s going well, why would I change?”
In his experience, at 2 years of immunotherapy, most patients “say they’re feeling great” and “don’t mind coming in every 4 or 6 weeks, depending on the drug,” said Dr. Goldman, director of clinical trials in thoracic oncology at UCLA Medical Center in Santa Monica, Calif.
Dr. Goldman noted that in the future, instead of continuing immunotherapy indefinitely, clinicians may aim to maintain the patient “in the best response possible,” adding an intervention, such as stereotactic body radiotherapy or radiologic ablation, when needed.
“It may be that many of these long-term disease control patients are not cured in a traditional sense,” Dr. Goldman said, “but have controlled cancer that could potentially last years or even decades with ongoing care.”
Dr. Sun has relationships with Regeneron, GenMab, Seagen, and Bayer and has received institutional funding from Blueprint Research, Seagen Research, and IO Biotech Research. Dr. West has relationships with AstraZeneca, Genentech/Roche, Merck, and Regeneron outside the submitted work. Dr. Reck has relationships with Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Daiichi-Sankyo, GSK, Lilly, Merck, MSD, Mirati, Novartis, Roche Regeneron, and Pfizer.
A version of this article appeared on Medscape.com.
Most patients with non–small cell lung cancer (NSCLC) who are long-term responders to immunotherapy will continue receiving treatment beyond 2 years. However, the best available evidence to date indicates that receiving immunotherapy after this 2-year mark likely offers no survival benefit.
Is it an overabundance of caution? A desire for more definitive data? Or is it simply a judgment call oncologists make on the basis of the individual patient?
Lova Sun, MD, MSCE, of the University of Pennsylvania in Philadelphia, believes the general inconsistency between the data and clinical practice “likely reflects significant hesitation on the part of clinicians, patients, or both to stop a treatment that is still ‘working.’ ”
H. Jack West, MD, agreed, adding that “in an ambiguous situation, a U.S.-based population is going to err on the side of overtreatment.”
Without “incontrovertible evidence” that immunotherapy should stop at 2 years, “many, many, many patients and clinicians are going to favor continuing ‘doing what you’re doing’ in the absence of either prohibitive toxicity or clinically significant disease progression,” said Dr. West of the City of Hope Comprehensive Cancer Center, Duarte, Calif.
One factor adding to this ambiguity: Most pivotal studies that examine first-line immunotherapy in NSCLC limit therapy duration to 2 years.
Another key factor is the absence of prospective data as to when to stop treatment for these patients, according to Martin Reck, MD, PhD, head of thoracic oncology at the Lung Clinic Grosshansdorf (Germany).
“We have never prospectively investigated the correlation of the duration of a checkpoint blockade and the efficacy of treatment,” Dr. Reck said. “And this is a big problem.” It means “we really do not know how long we should treat the patient.”
To make matters muddier, some data do suggest that more therapy may be better. The recent Checkmate 153 trial, for instance, found that patients who had no signs of disease progression and who received 1-year fixed-duration nivolumab had significantly shorter progression-free and overall survival than those who received treatment indefinitely.
However, randomized trials with longer-term follow-up suggest durable responses can be maintained for years after immunotherapy is stopped.
Data from the KEYNOTE-024 trial, for instance, showed that more than 45% of patients with metastatic NSCLC and high tumor PD-L1 expression who received pembrolizumab for 2 years remained alive at 5 years without further treatment or disease progression. Another trial, KEYNOTE-407, demonstrated similar 5-year survival outcomes among patients with advanced squamous NSCLC, regardless of PD-L1 status, who completed 2 years of chemotherapy plus pembrolizumab followed by maintenance pembrolizumab.
With these studies, however, “we can only speculate about whether the proportion of patients alive without progression would be substantially higher if treatment with immunotherapy continued longer,” Dr. West wrote in a recent editorial .
Perhaps the most telling data so far come from a recent retrospective analysis from Dr. Sun and colleagues. The researchers directly compared survival outcomes among patients who continued receiving immunotherapy indefinitely with outcomes among patients for whom immunotherapy was discontinued at 2 years.
The JAMA Oncology study, which focused on 706 patients with NSCLC who completed 2 years of therapy, found that only 16% stopped receiving immune checkpoint inhibitor therapy at 2 years, whereas the remaining 84% continued receiving treatment indefinitely.
Among patients who continued receiving immunotherapy for 2 additional years, overall survival was not better than among those who stopped receiving immunotherapy at the 2-year mark. Even among the 11 patients whose condition progressed when therapy was discontinued, most still did well after treatment was resumed.
However, the retrospective design of the study limits its impact.
Without more definitive “data about when the treatment can be stopped,” many continue “indefinitely as long as the patient is tolerating treatment and the disease is not progressing,” Conor E. Steuer, MD, and Suresh S. Ramalingam, MD, of Winship Cancer Institute at Emory University, Atlanta, wrote in a recent review.
Impact on practice?
Dr. Sun views her team’s findings not as a recommendation to halt immunotherapy for every patient at 2 years but rather as “one piece of data that may provide reassurance to providers and patients who wish to stop at 2 years.”
Ultimately, however, the decision as to when or whether to stop immunotherapy for long-term responders is “an individualized one that requires shared decision-making and consideration of each patient’s clinical history, preferences, and risk tolerance,” Dr. Sun explained.
Dr. Reck agreed, noting that until prospective trials evaluate a fixed approach, the duration of immunotherapy “has to be determined by the treating physician and the individual patient.”
For a patient with metastatic NSCLC who is having an excellent response to checkpoint blockade, “we are somewhat afraid to stop the immunotherapy,” explained Dr. Reck, “because we are afraid the disease might relapse.” However, he noted, for patients who have a stable response to therapy, it may make sense to consider discontinuing checkpoint blockade.
Outside of survival outcomes, oncologists should also consider quality of life. Stopping treatment at 2 years comes with a “lower risk of toxic effects, less time in treatment for patients, and considerably lower costs for our health care system,” said Dr. West.
But for a fixed strategy to become more standard practice, the burden of proof is high, Dr. West said.
Jonathan W. Goldman, MD, says he understands the mentality, “If it’s going well, why would I change?”
In his experience, at 2 years of immunotherapy, most patients “say they’re feeling great” and “don’t mind coming in every 4 or 6 weeks, depending on the drug,” said Dr. Goldman, director of clinical trials in thoracic oncology at UCLA Medical Center in Santa Monica, Calif.
Dr. Goldman noted that in the future, instead of continuing immunotherapy indefinitely, clinicians may aim to maintain the patient “in the best response possible,” adding an intervention, such as stereotactic body radiotherapy or radiologic ablation, when needed.
“It may be that many of these long-term disease control patients are not cured in a traditional sense,” Dr. Goldman said, “but have controlled cancer that could potentially last years or even decades with ongoing care.”
Dr. Sun has relationships with Regeneron, GenMab, Seagen, and Bayer and has received institutional funding from Blueprint Research, Seagen Research, and IO Biotech Research. Dr. West has relationships with AstraZeneca, Genentech/Roche, Merck, and Regeneron outside the submitted work. Dr. Reck has relationships with Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Daiichi-Sankyo, GSK, Lilly, Merck, MSD, Mirati, Novartis, Roche Regeneron, and Pfizer.
A version of this article appeared on Medscape.com.
Most patients with non–small cell lung cancer (NSCLC) who are long-term responders to immunotherapy will continue receiving treatment beyond 2 years. However, the best available evidence to date indicates that receiving immunotherapy after this 2-year mark likely offers no survival benefit.
Is it an overabundance of caution? A desire for more definitive data? Or is it simply a judgment call oncologists make on the basis of the individual patient?
Lova Sun, MD, MSCE, of the University of Pennsylvania in Philadelphia, believes the general inconsistency between the data and clinical practice “likely reflects significant hesitation on the part of clinicians, patients, or both to stop a treatment that is still ‘working.’ ”
H. Jack West, MD, agreed, adding that “in an ambiguous situation, a U.S.-based population is going to err on the side of overtreatment.”
Without “incontrovertible evidence” that immunotherapy should stop at 2 years, “many, many, many patients and clinicians are going to favor continuing ‘doing what you’re doing’ in the absence of either prohibitive toxicity or clinically significant disease progression,” said Dr. West of the City of Hope Comprehensive Cancer Center, Duarte, Calif.
One factor adding to this ambiguity: Most pivotal studies that examine first-line immunotherapy in NSCLC limit therapy duration to 2 years.
Another key factor is the absence of prospective data as to when to stop treatment for these patients, according to Martin Reck, MD, PhD, head of thoracic oncology at the Lung Clinic Grosshansdorf (Germany).
“We have never prospectively investigated the correlation of the duration of a checkpoint blockade and the efficacy of treatment,” Dr. Reck said. “And this is a big problem.” It means “we really do not know how long we should treat the patient.”
To make matters muddier, some data do suggest that more therapy may be better. The recent Checkmate 153 trial, for instance, found that patients who had no signs of disease progression and who received 1-year fixed-duration nivolumab had significantly shorter progression-free and overall survival than those who received treatment indefinitely.
However, randomized trials with longer-term follow-up suggest durable responses can be maintained for years after immunotherapy is stopped.
Data from the KEYNOTE-024 trial, for instance, showed that more than 45% of patients with metastatic NSCLC and high tumor PD-L1 expression who received pembrolizumab for 2 years remained alive at 5 years without further treatment or disease progression. Another trial, KEYNOTE-407, demonstrated similar 5-year survival outcomes among patients with advanced squamous NSCLC, regardless of PD-L1 status, who completed 2 years of chemotherapy plus pembrolizumab followed by maintenance pembrolizumab.
With these studies, however, “we can only speculate about whether the proportion of patients alive without progression would be substantially higher if treatment with immunotherapy continued longer,” Dr. West wrote in a recent editorial .
Perhaps the most telling data so far come from a recent retrospective analysis from Dr. Sun and colleagues. The researchers directly compared survival outcomes among patients who continued receiving immunotherapy indefinitely with outcomes among patients for whom immunotherapy was discontinued at 2 years.
The JAMA Oncology study, which focused on 706 patients with NSCLC who completed 2 years of therapy, found that only 16% stopped receiving immune checkpoint inhibitor therapy at 2 years, whereas the remaining 84% continued receiving treatment indefinitely.
Among patients who continued receiving immunotherapy for 2 additional years, overall survival was not better than among those who stopped receiving immunotherapy at the 2-year mark. Even among the 11 patients whose condition progressed when therapy was discontinued, most still did well after treatment was resumed.
However, the retrospective design of the study limits its impact.
Without more definitive “data about when the treatment can be stopped,” many continue “indefinitely as long as the patient is tolerating treatment and the disease is not progressing,” Conor E. Steuer, MD, and Suresh S. Ramalingam, MD, of Winship Cancer Institute at Emory University, Atlanta, wrote in a recent review.
Impact on practice?
Dr. Sun views her team’s findings not as a recommendation to halt immunotherapy for every patient at 2 years but rather as “one piece of data that may provide reassurance to providers and patients who wish to stop at 2 years.”
Ultimately, however, the decision as to when or whether to stop immunotherapy for long-term responders is “an individualized one that requires shared decision-making and consideration of each patient’s clinical history, preferences, and risk tolerance,” Dr. Sun explained.
Dr. Reck agreed, noting that until prospective trials evaluate a fixed approach, the duration of immunotherapy “has to be determined by the treating physician and the individual patient.”
For a patient with metastatic NSCLC who is having an excellent response to checkpoint blockade, “we are somewhat afraid to stop the immunotherapy,” explained Dr. Reck, “because we are afraid the disease might relapse.” However, he noted, for patients who have a stable response to therapy, it may make sense to consider discontinuing checkpoint blockade.
Outside of survival outcomes, oncologists should also consider quality of life. Stopping treatment at 2 years comes with a “lower risk of toxic effects, less time in treatment for patients, and considerably lower costs for our health care system,” said Dr. West.
But for a fixed strategy to become more standard practice, the burden of proof is high, Dr. West said.
Jonathan W. Goldman, MD, says he understands the mentality, “If it’s going well, why would I change?”
In his experience, at 2 years of immunotherapy, most patients “say they’re feeling great” and “don’t mind coming in every 4 or 6 weeks, depending on the drug,” said Dr. Goldman, director of clinical trials in thoracic oncology at UCLA Medical Center in Santa Monica, Calif.
Dr. Goldman noted that in the future, instead of continuing immunotherapy indefinitely, clinicians may aim to maintain the patient “in the best response possible,” adding an intervention, such as stereotactic body radiotherapy or radiologic ablation, when needed.
“It may be that many of these long-term disease control patients are not cured in a traditional sense,” Dr. Goldman said, “but have controlled cancer that could potentially last years or even decades with ongoing care.”
Dr. Sun has relationships with Regeneron, GenMab, Seagen, and Bayer and has received institutional funding from Blueprint Research, Seagen Research, and IO Biotech Research. Dr. West has relationships with AstraZeneca, Genentech/Roche, Merck, and Regeneron outside the submitted work. Dr. Reck has relationships with Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Daiichi-Sankyo, GSK, Lilly, Merck, MSD, Mirati, Novartis, Roche Regeneron, and Pfizer.
A version of this article appeared on Medscape.com.
Antigen tests: After pandemic success, time for bigger role?
Before the pandemic, most of the public probably had a fleeting and limited familiarity with lateral flow tests (LFTs), also known as rapid antigen tests. Perhaps they used, or awaited the results of, a lateral flow home pregnancy test, which detects human chorionic gonadotropin in urine.
Then came COVID-19, and the need for large-scale testing. By late 2022, more than 3 billion tests for SARS-CoV-2 had been done worldwide. Although testing with reverse-transcription polymerase chain reaction (PCR) is the gold standard for diagnosing COVID, LFTs made possible large-scale testing at low cost with rapid results.
As of Sept. 12, the Food and Drug Administration lists 32 rapid antigen tests with emergency use authorizations (EUAs) for home use.
Now, many experts conclude, it’s time to expand the role of LFTs so the technology can help detect a host of other diseases. In a Nature Reviews bioengineering report, global experts from the United States, the United Kingdom, and other countries pointed out that commercial LFTs are currently not available for four of the eight known priority diseases of epidemic potential: Crimean-Congo hemorrhagic fever, Middle East respiratory syndrome coronavirus, Nipah and other henipaviruses, and Rift Valley fever.
Expansion should not only include more tests for more diseases, some experts say, but also make use of existing technology to provide “full-circle” care. After a rapid test, for instance, users could download a mobile phone app, transmit the results to their health care provider, and then set up an appointment if needed or get a prescribed medication at the pharmacy.
Medical community on board
Clinicians support increased availability of LFTs, said Eric J. Topol, MD, professor and executive vice president of Scripps Research, La Jolla, Calif.“Rapid antigen tests are critical, made a big difference in the pandemic, and will be used increasingly for many other applications in the years ahead,” Dr. Topol said in an email.
Physicians welcome their potential, agreed William Schaffner, MD, professor of preventive medicine and infectious disease specialist at Vanderbilt University Medical Center, Nashville, Tenn. At the start of the pandemic, when he was briefed about a lateral flow device in development, he said, “I was blown away by the technology, ease of use, rapidity of getting a result, its reasonable accuracy and its anticipated relatively low price.”
Clinicians would probably see many advantages to having more LFTs for more diseases, Dr. Schaffner said, because they are of use not only at home but also in doctors’ offices and in emergency departments. Their increased use “would help [people] make quick decisions about treatment, especially for flu and COVID.”
How LFTs work
LFTs are capable of targeting antigens, such as for the COVID tests, and antibodies such as IgG or IgM. The tests are also capable of detecting nucleic acids, although the availability of these tests is currently rare.
First, a sample from blood, urine, saliva or other bodily sources is placed onto a sample pad. It travels to a conjugate pad containing antibodies. If the target being looked for is present, the target and antibodies bind and, as the sample moves along to the test line, produces a positive result line along with the control line (to show that the test worked).
Global market outlook
By 2030, the lateral flow assays market is predicted to rise to $14.1 billion, according to a report issued in September by the firm Research and Markets. In 2022, the market was estimated at $9.4 billion, with $3.6 billion of that in the United States.
The report details the performances of 55 major competitors, such as Abbott Laboratories, Siemens, and QuidelOrtho, but smaller companies and start-ups are also involved in LFT development.
LFTs: Pros and cons
Although LFTs give rapid results, their accuracy is lower than that of PCR, especially the sensitivity. For COVID antigen LFTs, the sensitivity ranges from 34.1% to 88.1%, with an overall specificity of 99.6%, according to a Cochrane Review report. The analytical sensitivity performance of PCR testing for COVID is near 100%.
Everyone acknowledges the accuracy challenge of LFTs. The technologies “are generally thought to have limitations of detection that for some applications may present a challenge,” said Douglas C. Bryant, president and CEO of QuidelOrtho, San Diego, which counts the QuickVue rapid test for COVID detection among its products.
However, Mr. Bryant added, “as we saw during the pandemic, there was a place for more sensitive PCR-based technologies that are often run in a lab and there was a place for the use of rapid tests: The key is knowing the strengths and best use cases when applying the different technologies.”
One strength, he said, was that the tests “were shown to be highly effective at detecting active, infectious cases of SARS-CoV-2 and the rapid turnaround time allowed patients to isolate themselves from others quickly to help curb the spread of infection to others.” Another advantage was the ability to screen high-risk populations such as nursing homes to detect positive cases and help prevent outbreaks.
The pandemic familiarized people with the tests, said Jeremy Stackawitz, CEO of Senzo, a start-up in vitro diagnostics company developing an amplified LFT platform for rapid tests for flu, tuberculosis, COVID, and Clostridioides difficile. People liked using them. Physicians generally accepted them. It works great with tele-doc. It works great with personalized medicine.
Now, he said, people used to the COVID self-tests are asking: “Where is my strep test? Where is my sexual health test?”
FDA’s perspective on LFTs
The FDA has no one-size-fits-all standard for evaluating LFTs.
“LFTs are evaluated with respect to their individual indications and the pathway under which they are being reviewed,” said James McKinney, an FDA spokesperson. “A performance recommendation for one type of lateral flow test may not be appropriate for another.”
EUAs, such as those given for the COVID at-home tests, require different levels of evidence than traditional premarket review, he said, whether de novo marketing authorization, 510(k) premarket notification, or premarket approval. The EUAs are evaluated with a risk-benefit analysis to speed up the time it takes to make the devices available.
And, Mr. McKinney said, for some devices, the FDA provides recommendations on the expected performance through guidance documents. For instance, for rapid devices developed to detect influenza A virus antigen, the FDA recommends including enough sample to generate sensitivity of greater than 60% and testing at least 50 samples.
LFTs: The potential, the challenges
Mr. Stackawitz predicted that, as more LFT self-tests become available, more people will seek care, just as they did with the COVID rapid tests. A 22-year-old who thinks he has chlamydia may balk at going to a doctor right away. However, “if he can go buy a soda and a test at CVS, it’s different, it really is. With a little anonymity, people will seek care.”
He has a vision shared by other experts: That testing technology will evolve so that after getting the results at home, people would follow through by sending those results to their health care provider and obtaining needed care or medication. In his opinion, this is superior to the traditional way, which often involves visiting a doctor with symptoms, going for tests, waiting for results, and then beginning treatment.
“It would make more sense if you came in knowing your results,” Mr. Stackawitz said. “It’s a much smarter pathway, gives better outcomes for the patient, is much quicker and at much less cost. And it frees up time for doctors. I think most physicians would embrace that.”
Although rapid testing is gaining well-deserved recognition, funding is an issue, according to the Nature Reviews report. Those experts warned that “a reduction in funding for LFT research post COVID-19 may hamper efforts to capitalize on gains in decentralized testing, especially self-testing, which may be critical to address future pandemic threats.”
A version of this article first appeared on Medscape.com.
Before the pandemic, most of the public probably had a fleeting and limited familiarity with lateral flow tests (LFTs), also known as rapid antigen tests. Perhaps they used, or awaited the results of, a lateral flow home pregnancy test, which detects human chorionic gonadotropin in urine.
Then came COVID-19, and the need for large-scale testing. By late 2022, more than 3 billion tests for SARS-CoV-2 had been done worldwide. Although testing with reverse-transcription polymerase chain reaction (PCR) is the gold standard for diagnosing COVID, LFTs made possible large-scale testing at low cost with rapid results.
As of Sept. 12, the Food and Drug Administration lists 32 rapid antigen tests with emergency use authorizations (EUAs) for home use.
Now, many experts conclude, it’s time to expand the role of LFTs so the technology can help detect a host of other diseases. In a Nature Reviews bioengineering report, global experts from the United States, the United Kingdom, and other countries pointed out that commercial LFTs are currently not available for four of the eight known priority diseases of epidemic potential: Crimean-Congo hemorrhagic fever, Middle East respiratory syndrome coronavirus, Nipah and other henipaviruses, and Rift Valley fever.
Expansion should not only include more tests for more diseases, some experts say, but also make use of existing technology to provide “full-circle” care. After a rapid test, for instance, users could download a mobile phone app, transmit the results to their health care provider, and then set up an appointment if needed or get a prescribed medication at the pharmacy.
Medical community on board
Clinicians support increased availability of LFTs, said Eric J. Topol, MD, professor and executive vice president of Scripps Research, La Jolla, Calif.“Rapid antigen tests are critical, made a big difference in the pandemic, and will be used increasingly for many other applications in the years ahead,” Dr. Topol said in an email.
Physicians welcome their potential, agreed William Schaffner, MD, professor of preventive medicine and infectious disease specialist at Vanderbilt University Medical Center, Nashville, Tenn. At the start of the pandemic, when he was briefed about a lateral flow device in development, he said, “I was blown away by the technology, ease of use, rapidity of getting a result, its reasonable accuracy and its anticipated relatively low price.”
Clinicians would probably see many advantages to having more LFTs for more diseases, Dr. Schaffner said, because they are of use not only at home but also in doctors’ offices and in emergency departments. Their increased use “would help [people] make quick decisions about treatment, especially for flu and COVID.”
How LFTs work
LFTs are capable of targeting antigens, such as for the COVID tests, and antibodies such as IgG or IgM. The tests are also capable of detecting nucleic acids, although the availability of these tests is currently rare.
First, a sample from blood, urine, saliva or other bodily sources is placed onto a sample pad. It travels to a conjugate pad containing antibodies. If the target being looked for is present, the target and antibodies bind and, as the sample moves along to the test line, produces a positive result line along with the control line (to show that the test worked).
Global market outlook
By 2030, the lateral flow assays market is predicted to rise to $14.1 billion, according to a report issued in September by the firm Research and Markets. In 2022, the market was estimated at $9.4 billion, with $3.6 billion of that in the United States.
The report details the performances of 55 major competitors, such as Abbott Laboratories, Siemens, and QuidelOrtho, but smaller companies and start-ups are also involved in LFT development.
LFTs: Pros and cons
Although LFTs give rapid results, their accuracy is lower than that of PCR, especially the sensitivity. For COVID antigen LFTs, the sensitivity ranges from 34.1% to 88.1%, with an overall specificity of 99.6%, according to a Cochrane Review report. The analytical sensitivity performance of PCR testing for COVID is near 100%.
Everyone acknowledges the accuracy challenge of LFTs. The technologies “are generally thought to have limitations of detection that for some applications may present a challenge,” said Douglas C. Bryant, president and CEO of QuidelOrtho, San Diego, which counts the QuickVue rapid test for COVID detection among its products.
However, Mr. Bryant added, “as we saw during the pandemic, there was a place for more sensitive PCR-based technologies that are often run in a lab and there was a place for the use of rapid tests: The key is knowing the strengths and best use cases when applying the different technologies.”
One strength, he said, was that the tests “were shown to be highly effective at detecting active, infectious cases of SARS-CoV-2 and the rapid turnaround time allowed patients to isolate themselves from others quickly to help curb the spread of infection to others.” Another advantage was the ability to screen high-risk populations such as nursing homes to detect positive cases and help prevent outbreaks.
The pandemic familiarized people with the tests, said Jeremy Stackawitz, CEO of Senzo, a start-up in vitro diagnostics company developing an amplified LFT platform for rapid tests for flu, tuberculosis, COVID, and Clostridioides difficile. People liked using them. Physicians generally accepted them. It works great with tele-doc. It works great with personalized medicine.
Now, he said, people used to the COVID self-tests are asking: “Where is my strep test? Where is my sexual health test?”
FDA’s perspective on LFTs
The FDA has no one-size-fits-all standard for evaluating LFTs.
“LFTs are evaluated with respect to their individual indications and the pathway under which they are being reviewed,” said James McKinney, an FDA spokesperson. “A performance recommendation for one type of lateral flow test may not be appropriate for another.”
EUAs, such as those given for the COVID at-home tests, require different levels of evidence than traditional premarket review, he said, whether de novo marketing authorization, 510(k) premarket notification, or premarket approval. The EUAs are evaluated with a risk-benefit analysis to speed up the time it takes to make the devices available.
And, Mr. McKinney said, for some devices, the FDA provides recommendations on the expected performance through guidance documents. For instance, for rapid devices developed to detect influenza A virus antigen, the FDA recommends including enough sample to generate sensitivity of greater than 60% and testing at least 50 samples.
LFTs: The potential, the challenges
Mr. Stackawitz predicted that, as more LFT self-tests become available, more people will seek care, just as they did with the COVID rapid tests. A 22-year-old who thinks he has chlamydia may balk at going to a doctor right away. However, “if he can go buy a soda and a test at CVS, it’s different, it really is. With a little anonymity, people will seek care.”
He has a vision shared by other experts: That testing technology will evolve so that after getting the results at home, people would follow through by sending those results to their health care provider and obtaining needed care or medication. In his opinion, this is superior to the traditional way, which often involves visiting a doctor with symptoms, going for tests, waiting for results, and then beginning treatment.
“It would make more sense if you came in knowing your results,” Mr. Stackawitz said. “It’s a much smarter pathway, gives better outcomes for the patient, is much quicker and at much less cost. And it frees up time for doctors. I think most physicians would embrace that.”
Although rapid testing is gaining well-deserved recognition, funding is an issue, according to the Nature Reviews report. Those experts warned that “a reduction in funding for LFT research post COVID-19 may hamper efforts to capitalize on gains in decentralized testing, especially self-testing, which may be critical to address future pandemic threats.”
A version of this article first appeared on Medscape.com.
Before the pandemic, most of the public probably had a fleeting and limited familiarity with lateral flow tests (LFTs), also known as rapid antigen tests. Perhaps they used, or awaited the results of, a lateral flow home pregnancy test, which detects human chorionic gonadotropin in urine.
Then came COVID-19, and the need for large-scale testing. By late 2022, more than 3 billion tests for SARS-CoV-2 had been done worldwide. Although testing with reverse-transcription polymerase chain reaction (PCR) is the gold standard for diagnosing COVID, LFTs made possible large-scale testing at low cost with rapid results.
As of Sept. 12, the Food and Drug Administration lists 32 rapid antigen tests with emergency use authorizations (EUAs) for home use.
Now, many experts conclude, it’s time to expand the role of LFTs so the technology can help detect a host of other diseases. In a Nature Reviews bioengineering report, global experts from the United States, the United Kingdom, and other countries pointed out that commercial LFTs are currently not available for four of the eight known priority diseases of epidemic potential: Crimean-Congo hemorrhagic fever, Middle East respiratory syndrome coronavirus, Nipah and other henipaviruses, and Rift Valley fever.
Expansion should not only include more tests for more diseases, some experts say, but also make use of existing technology to provide “full-circle” care. After a rapid test, for instance, users could download a mobile phone app, transmit the results to their health care provider, and then set up an appointment if needed or get a prescribed medication at the pharmacy.
Medical community on board
Clinicians support increased availability of LFTs, said Eric J. Topol, MD, professor and executive vice president of Scripps Research, La Jolla, Calif.“Rapid antigen tests are critical, made a big difference in the pandemic, and will be used increasingly for many other applications in the years ahead,” Dr. Topol said in an email.
Physicians welcome their potential, agreed William Schaffner, MD, professor of preventive medicine and infectious disease specialist at Vanderbilt University Medical Center, Nashville, Tenn. At the start of the pandemic, when he was briefed about a lateral flow device in development, he said, “I was blown away by the technology, ease of use, rapidity of getting a result, its reasonable accuracy and its anticipated relatively low price.”
Clinicians would probably see many advantages to having more LFTs for more diseases, Dr. Schaffner said, because they are of use not only at home but also in doctors’ offices and in emergency departments. Their increased use “would help [people] make quick decisions about treatment, especially for flu and COVID.”
How LFTs work
LFTs are capable of targeting antigens, such as for the COVID tests, and antibodies such as IgG or IgM. The tests are also capable of detecting nucleic acids, although the availability of these tests is currently rare.
First, a sample from blood, urine, saliva or other bodily sources is placed onto a sample pad. It travels to a conjugate pad containing antibodies. If the target being looked for is present, the target and antibodies bind and, as the sample moves along to the test line, produces a positive result line along with the control line (to show that the test worked).
Global market outlook
By 2030, the lateral flow assays market is predicted to rise to $14.1 billion, according to a report issued in September by the firm Research and Markets. In 2022, the market was estimated at $9.4 billion, with $3.6 billion of that in the United States.
The report details the performances of 55 major competitors, such as Abbott Laboratories, Siemens, and QuidelOrtho, but smaller companies and start-ups are also involved in LFT development.
LFTs: Pros and cons
Although LFTs give rapid results, their accuracy is lower than that of PCR, especially the sensitivity. For COVID antigen LFTs, the sensitivity ranges from 34.1% to 88.1%, with an overall specificity of 99.6%, according to a Cochrane Review report. The analytical sensitivity performance of PCR testing for COVID is near 100%.
Everyone acknowledges the accuracy challenge of LFTs. The technologies “are generally thought to have limitations of detection that for some applications may present a challenge,” said Douglas C. Bryant, president and CEO of QuidelOrtho, San Diego, which counts the QuickVue rapid test for COVID detection among its products.
However, Mr. Bryant added, “as we saw during the pandemic, there was a place for more sensitive PCR-based technologies that are often run in a lab and there was a place for the use of rapid tests: The key is knowing the strengths and best use cases when applying the different technologies.”
One strength, he said, was that the tests “were shown to be highly effective at detecting active, infectious cases of SARS-CoV-2 and the rapid turnaround time allowed patients to isolate themselves from others quickly to help curb the spread of infection to others.” Another advantage was the ability to screen high-risk populations such as nursing homes to detect positive cases and help prevent outbreaks.
The pandemic familiarized people with the tests, said Jeremy Stackawitz, CEO of Senzo, a start-up in vitro diagnostics company developing an amplified LFT platform for rapid tests for flu, tuberculosis, COVID, and Clostridioides difficile. People liked using them. Physicians generally accepted them. It works great with tele-doc. It works great with personalized medicine.
Now, he said, people used to the COVID self-tests are asking: “Where is my strep test? Where is my sexual health test?”
FDA’s perspective on LFTs
The FDA has no one-size-fits-all standard for evaluating LFTs.
“LFTs are evaluated with respect to their individual indications and the pathway under which they are being reviewed,” said James McKinney, an FDA spokesperson. “A performance recommendation for one type of lateral flow test may not be appropriate for another.”
EUAs, such as those given for the COVID at-home tests, require different levels of evidence than traditional premarket review, he said, whether de novo marketing authorization, 510(k) premarket notification, or premarket approval. The EUAs are evaluated with a risk-benefit analysis to speed up the time it takes to make the devices available.
And, Mr. McKinney said, for some devices, the FDA provides recommendations on the expected performance through guidance documents. For instance, for rapid devices developed to detect influenza A virus antigen, the FDA recommends including enough sample to generate sensitivity of greater than 60% and testing at least 50 samples.
LFTs: The potential, the challenges
Mr. Stackawitz predicted that, as more LFT self-tests become available, more people will seek care, just as they did with the COVID rapid tests. A 22-year-old who thinks he has chlamydia may balk at going to a doctor right away. However, “if he can go buy a soda and a test at CVS, it’s different, it really is. With a little anonymity, people will seek care.”
He has a vision shared by other experts: That testing technology will evolve so that after getting the results at home, people would follow through by sending those results to their health care provider and obtaining needed care or medication. In his opinion, this is superior to the traditional way, which often involves visiting a doctor with symptoms, going for tests, waiting for results, and then beginning treatment.
“It would make more sense if you came in knowing your results,” Mr. Stackawitz said. “It’s a much smarter pathway, gives better outcomes for the patient, is much quicker and at much less cost. And it frees up time for doctors. I think most physicians would embrace that.”
Although rapid testing is gaining well-deserved recognition, funding is an issue, according to the Nature Reviews report. Those experts warned that “a reduction in funding for LFT research post COVID-19 may hamper efforts to capitalize on gains in decentralized testing, especially self-testing, which may be critical to address future pandemic threats.”
A version of this article first appeared on Medscape.com.
Beyond cystic fibrosis: Genetics of PF and other lung diseases
The remarkable story of cystic fibrosis (CF) – from gene discovery in 1989 to highly effective precision-medicine therapies today – inspires Christine Kim Garcia, MD, PhD, as she searches for rare mutations in genes linked to inherited forms of lung fibrosis, termed familial pulmonary fibrosis (FPF).
“Cystic fibrosis has provided a framework for approaching the genetics of lung fibrosis,” said Dr. Garcia, Frode Jensen Professor of Medicine and chief of the pulmonology, allergy, and critical care medicine division at Columbia University, and director of the Columbia Precision Medicine Initiative, both in New York.
Pulmonary fibrosis is more complicated than CF. “Mutations in more than 10 different genes can lead to the increased heritable risk of pulmonary fibrosis that we find in families. Different mutations exist for each gene. Sometimes the mutations are so rare that they are only found in a single family,” she said. “In addition, different subtypes of fibrotic interstitial lung disease can be linked to the same mutation and found in the same family.”
Despite these complexities, genetic discoveries in PF have illuminated pathophysiologic pathways and are driving the research that Dr. Garcia and other experts hope will lead to helpful prognostic tools and to precision therapies. And already, at institutions like Columbia, genetic discoveries are changing clinical care, driving treatment decisions and spurring family screening.
Thomas Ferkol, MD, whose research focuses on genetic factors that contribute to suppurative airway diseases such as CF and primary ciliary dyskinesia (PCD), similarly regards CF as a road map for genetics research and genetic testing in practice.
“The treatments we’re doing now for CF are increasingly based on the genetics of the individual,” said Dr. Ferkol, professor and division chief for pediatric pulmonology at the University of North Carolina at Chapel Hill, where the UNC Children’s Hospital hosts a rare and genetic lung disease program. For PCD, genetic testing has become a front-line diagnostic tool. But in the future, he hopes, it will also become a determinant for personalized treatment for children with PCD.
The cystic fibrosis transmembrane conductance regulator (CFTR) gene was the first lung disease gene to be discovered using gene-mapping techniques. Since then, and especially in the last 15-20 years, “there’s been a lot of progress in the identification of genes for which mutations and variations cause specific forms of pulmonary disease, many of which can now establish a firm diagnosis, and some of which lead to very directed changes in management. There has also been great progress in the availability of genetic testing,” said Benjamin A. Raby, MD, MPH, director of the Pulmonary Genetics Center at Brigham and Women’s Hospital, Boston, which sees patients with a host of cystic lung diseases, bronchiectasic lung diseases, fibrotic lung diseases, and other conditions, including pulmonary fibrosis and PCD.
Pulmonary fibrosis in adults and PCD in children are two examples of lung diseases for which genetic discoveries have exploded in recent years, with important implications for care now and in the future.
Leveraging genetic testing in PF
FPF describes families with two or more members with PF within three degrees of relationship; it is a designation believed to affect 20%-25% of people with PF and occurs predominantly later in the adult years (after 50 years of age), most commonly in autosomal dominant fashion, and amidst a stew of genetic risks, environmental exposures, and other insults.
Dr. Garcia and other researchers have uncovered two main types of genes in which rare variants can give rise to a heritable risk of FP: Genes that contribute to the maintenance of telomere length, and genes involved in surfactant metabolism. [Last year, Dr. Garcia and colleagues reported their discovery of both rare and common variants in a “spindle gene,” KIF15, in patients with IPF, suggesting an additional pathogenic pathway. The gene controls dynamics of cell division. (Am J Respir Crit Care Med. 2022;206[1]:p 56-69.)]
Detection of telomere pathway involvement – most commonly involving the TERT gene – is consequential because patients with telomere-associated gene mutations “tend to progress faster and have a more aggressive disease course than patients without these mutations … regardless of how their scans or biopsies look,” as do patients who have short age-adjusted telomere length, said Dr. Chad Newton, MD, who directs the Interstitial Lung Disease program at the University of Texas Southwestern and researches the genetics of ILD.
Dr. Newton and Dr. Garcia advise patients with PF and a positive family history to undergo panel-based genetic sequencing, along with telomere length measurement. They also advise that undiagnosed first-degree relatives consider what’s called “cascade testing” – genetic sequencing for any pathogenic or likely pathogenic rare variants found in the patient’s investigation. (Dr. Garcia, who cochairs a National Institutes of Health–funded interstitial lung disease curation panel, said she finds evidence of a pathogenic or likely pathogenic variant in about 25% of patients with a family history of PF.)
“We can use this genetic information to consider starting early [antifibrotic] treatment to try to delay progression … just as we would with other forms of pulmonary fibrosis,” Dr. Newton said, “and to expand our reach to others not sitting in our clinics who have the same rare condition or are at risk.”
After cascade testing, Dr. Garcia said, she invites family members with positive results to have baseline CT scans and pulmonary function testing. “And if there’s anything abnormal, we’re inviting them to have regular follow-up testing,” she said, “because we advise starting antifibrotic treatment at the very first sign of disease worsening.”
Such an approach to genetic testing for patients and relatives is described in a statement commissioned by the Pulmonary Fibrosis Foundation and published last year in the journal Chest (2022:162[2]:394-405). The statement, for which Dr. Newton and Dr. Garcia were among the authors, also lists clinical features within patients and families suggestive of a possible genetic pathway, and describes the potential yield for identifying a variant in different clinical scenarios.
Pathogenic variants in telomere genes as well as findings of short telomere length are associated with various extrapulmonary manifestations such as liver dysfunction, bone marrow dysfunction, and head and neck cancers, Dr. Newton said, making surveillance and referrals important. (Rare variants and short telomere length are associated with disease progression across several non-IPF diagnoses as well.)
Moreover, short telomeres may signal the need to avoid long-term immunosuppression. Research published in 2019 from multiple cohorts, and led by Dr. Newton and Dr. Garcia, showed that short telomere length is associated with worse outcomes (faster time to composite death, transplant, FVC decline, and hospitalization) in patients with IPF who received immunosuppression. These adverse outcomes were not found in IPF patients with normal telomere lengths who received similar immunosuppression (Am J Respir Crit Care Med. 2019;200(3):336-347).
Gene sequencing and telomere length measurement are described in the 2020 Chest statement on the role of genetic testing in PF as yielding “different yet complementary information.” Short age-adjusted telomere length (less than the 10th percentile) is common in those with pathogenic variants in telomere genes, but it can also occur in the absence of identifiable rare telomere-related variants, the statement says. Telomere length testing can be helpful, it notes, in determining the significance of a “variant of unknown significance (VUS)” if gene sequencing identifies one.
The future of genetic screening for PF
Future genetic screening approaches for PF may cast an even wider net while better stratifying risk for family members. At Brigham and Women’s Hospital, where family screening was a major impetus for the 2008 founding of the Pulmonary Genetics Center, research published several years ago by Dr. Raby and his colleagues found that 31% of 107 asymptomatic first-degree relatives of patients with PF had interstitial lung abnormalities on chest CTs – whether or not a family history was reported – and 18% had clear radiographic or physiological manifestations of fibrosis (Am J Respir Crit Care Med. 2020;201[10]:1240-8).
“That’s more than 10-fold higher than what we thought we’d see, based on prior literature. … And the numbers were pretty much the same whether or not there was a family history of fibrosis reported by the patient,” said Dr. Raby, also the Leila and Irving Perlmutter professor of pediatrics at Harvard Medical School, Boston, and chief of the division of pulmonary medicine at Boston Children’s Hospital. “We used to think we only needed to worry about genetic risk when there was a family history. But now we see that sporadic cases are also driven by genetics.”
Their study also included a 2-year follow-up chest CT, in which the majority of the screened relatives participated. Of those, 65% who had interstitial changes at baseline showed progression. Four percent of those without interstitial abnormalities at baseline developed abnormalities (Am J Respir Crit Care Med. 2023;207[2]:211-4). “The fact that 65% progressed suggests that in the majority of patients what we’re finding is something that’s real and is going to be clinically meaningful for patients,” he said.
Genetic signatures
A next phase of research at Brigham & Women’s and Boston Children’s, he said, will address PF’s “complex genetic signature” and test polygenic risk scores for idiopathic PF that take into account not only rare genetic variants that can be solidly linked to disease but many common genetic variants being detected in genome-wide association studies. [By definition, common variants, otherwise known as single-nucleotide polymorphisms (SNPs) occur with greater frequency in the general population (> 5%), generally reside within noncoding regions, and may contribute to disease risk but alone do not cause disease.]
“As technologies and genetic studies improve, we’re seeing we can estimate much better the likelihood of disease than we could 10 years ago,” he said. A “potent” common variant called the MUC5B promoter polymorphism has been shown to confer a 3-fold to 20-fold increased risk for PF, he noted. (Polygenic risk scores are also being developed, he said, for asthma and chronic obstructive pulmonary disease.)
“Every time one sees a patient with PF that is thought to be idiopathic one should start thinking about their at-risk family members, particularly their siblings,” Dr. Raby said. But in doing so, “wouldn’t it be wonderful if we could use polygenic risk scores to assure some [family members] that they’re in the lowest tier of risk and might need pulmonary function studies every 5 years, for example, versus someone we’d want to see more frequently, versus someone [for whom] we’d want to start preventive therapy at the earlier signs of declining lung function?”
Moving forward, he and the others said, the field needs more research to determine how genetic risk factors predict disease progression and prospective clinical trials to test whether long-term outcomes are indeed improved by early institution of antifibrotic therapy and other genetics-driven management decisions. “The data we’re using to inform prognosis and treatment decisions are compelling, but a lot of it is based on cohort studies and retrospective research,” Dr. Newton said.
Multi-institutional transomics studies and other research projects are underway, meanwhile, to build upon gene identifications and learn more about the pathobiology of PF. “We know about two big genetic pathways … but we need to sort it all out,” he said. For instance, “are there intermediate pathways? And where does it actually start? What kind of cell?”
Genetics’ impact on PCD
About 20 years ago, only two genes were linked to PCD, a largely autosomal recessive disorder that results from abnormalities in the cilia and subsequently improper airway clearance. Today, said Dr. Ferkol, there are over 50 known genes that, if defective, can lead to PCD.
“Based on our latest estimates, I’d say we can diagnose people using genetics about 70%, maybe 80%, of the time,” Dr. Ferkol said. Genetic testing has become a first-line diagnostic tool for PCD in North America – a significant development given that a definitive diagnosis has long been challenging, he said.
A genetics-based diagnosis of PCD is sometimes challenged by the finding of variants of unknown significance (VUSs) on genetic testing (often missense mutations) “because some of the genes involved are huge,” noted Dr. Ferkol, who coleads the NIH-funded Genetic Disorders of Mucociliary Clearance Consortium. “But many times, it’s straightforward.”
Children with PCD have repeated or persistent upper respiratory tract infections beginning early in life – like chronic rhinosinusitis or suppurative otitis media – and chronic bronchitis, leading to bronchiectasis. About half of patients have a spectrum of laterality defects, where organs are malpositioned in a mirror image of normal. Some individuals also have cardiac defects, and subfertility in both males and females can frequently occur.
Just as it has become increasingly clear that CF exists as a continuum, with milder and variant forms having been recognized since the advent of genetic testing, “we’re finding genotype-phenotype relationships in PCD,” Dr. Ferkol said. “Certain individuals have more rapid pulmonary decline, which is related in part to their genetics.”
With PCD, “I’m convinced this is a continuum. Some patients have unmistakable, clear-cut PCD, but I’m sure we’re going to find individuals who have milder variants in these PCD-associated genes that lead to milder disease,” he said.
There are no specific treatments that will correct cilia dysfunction, and current therapy options are borrowed from other diseases such as asthma and CF. However, newer treatments targeting specific genetic defects are in early clinical studies. Will the gene discoveries and more research open up new avenues for treating PCD, as happened in CF? Dr. Ferkol hopes so.
Approximately 2,000 genetic variants have been identified in the CFTR gene, though not all are pathogenic. “The newer, highly effective modulators used in CF target a particular CFTR mutation class, so some drugs will work for some people with the disease, but not all,” Dr. Ferkol said. “It’s personalized medicine.”
Modulator therapies designed to correct the malfunctioning proteins made by the CFTR gene have profoundly changed the lives of many with CF, improving lung function and everyday symptoms for patients, allowing them to lead near-normal lives. “It’s astonishing,” he said.
Dr. Garcia reported consulting for Rejuvenation Technologies and Rejuveron Telomere Therapeutics; in addition, her laboratory has received support from Boehringer Ingelheim and Astrazeneca for investigator-initiated research. Dr. Newton reported he has performed consulting for Boehringer Ingelheim. Dr. Ferkol reported involvement in a longitudinal study defining endpoints for future clinical PCD trials funded by ReCode Therapeutics and leadership of an international clinical trial for PCD supported by Parion Sciences. He has received honoraria from the Cystic Fibrosis Foundation and serves as a member of the ReCode Therapeutics PCD Clinical Steering Committee. Dr. Raby reported no relevant disclosures.
The remarkable story of cystic fibrosis (CF) – from gene discovery in 1989 to highly effective precision-medicine therapies today – inspires Christine Kim Garcia, MD, PhD, as she searches for rare mutations in genes linked to inherited forms of lung fibrosis, termed familial pulmonary fibrosis (FPF).
“Cystic fibrosis has provided a framework for approaching the genetics of lung fibrosis,” said Dr. Garcia, Frode Jensen Professor of Medicine and chief of the pulmonology, allergy, and critical care medicine division at Columbia University, and director of the Columbia Precision Medicine Initiative, both in New York.
Pulmonary fibrosis is more complicated than CF. “Mutations in more than 10 different genes can lead to the increased heritable risk of pulmonary fibrosis that we find in families. Different mutations exist for each gene. Sometimes the mutations are so rare that they are only found in a single family,” she said. “In addition, different subtypes of fibrotic interstitial lung disease can be linked to the same mutation and found in the same family.”
Despite these complexities, genetic discoveries in PF have illuminated pathophysiologic pathways and are driving the research that Dr. Garcia and other experts hope will lead to helpful prognostic tools and to precision therapies. And already, at institutions like Columbia, genetic discoveries are changing clinical care, driving treatment decisions and spurring family screening.
Thomas Ferkol, MD, whose research focuses on genetic factors that contribute to suppurative airway diseases such as CF and primary ciliary dyskinesia (PCD), similarly regards CF as a road map for genetics research and genetic testing in practice.
“The treatments we’re doing now for CF are increasingly based on the genetics of the individual,” said Dr. Ferkol, professor and division chief for pediatric pulmonology at the University of North Carolina at Chapel Hill, where the UNC Children’s Hospital hosts a rare and genetic lung disease program. For PCD, genetic testing has become a front-line diagnostic tool. But in the future, he hopes, it will also become a determinant for personalized treatment for children with PCD.
The cystic fibrosis transmembrane conductance regulator (CFTR) gene was the first lung disease gene to be discovered using gene-mapping techniques. Since then, and especially in the last 15-20 years, “there’s been a lot of progress in the identification of genes for which mutations and variations cause specific forms of pulmonary disease, many of which can now establish a firm diagnosis, and some of which lead to very directed changes in management. There has also been great progress in the availability of genetic testing,” said Benjamin A. Raby, MD, MPH, director of the Pulmonary Genetics Center at Brigham and Women’s Hospital, Boston, which sees patients with a host of cystic lung diseases, bronchiectasic lung diseases, fibrotic lung diseases, and other conditions, including pulmonary fibrosis and PCD.
Pulmonary fibrosis in adults and PCD in children are two examples of lung diseases for which genetic discoveries have exploded in recent years, with important implications for care now and in the future.
Leveraging genetic testing in PF
FPF describes families with two or more members with PF within three degrees of relationship; it is a designation believed to affect 20%-25% of people with PF and occurs predominantly later in the adult years (after 50 years of age), most commonly in autosomal dominant fashion, and amidst a stew of genetic risks, environmental exposures, and other insults.
Dr. Garcia and other researchers have uncovered two main types of genes in which rare variants can give rise to a heritable risk of FP: Genes that contribute to the maintenance of telomere length, and genes involved in surfactant metabolism. [Last year, Dr. Garcia and colleagues reported their discovery of both rare and common variants in a “spindle gene,” KIF15, in patients with IPF, suggesting an additional pathogenic pathway. The gene controls dynamics of cell division. (Am J Respir Crit Care Med. 2022;206[1]:p 56-69.)]
Detection of telomere pathway involvement – most commonly involving the TERT gene – is consequential because patients with telomere-associated gene mutations “tend to progress faster and have a more aggressive disease course than patients without these mutations … regardless of how their scans or biopsies look,” as do patients who have short age-adjusted telomere length, said Dr. Chad Newton, MD, who directs the Interstitial Lung Disease program at the University of Texas Southwestern and researches the genetics of ILD.
Dr. Newton and Dr. Garcia advise patients with PF and a positive family history to undergo panel-based genetic sequencing, along with telomere length measurement. They also advise that undiagnosed first-degree relatives consider what’s called “cascade testing” – genetic sequencing for any pathogenic or likely pathogenic rare variants found in the patient’s investigation. (Dr. Garcia, who cochairs a National Institutes of Health–funded interstitial lung disease curation panel, said she finds evidence of a pathogenic or likely pathogenic variant in about 25% of patients with a family history of PF.)
“We can use this genetic information to consider starting early [antifibrotic] treatment to try to delay progression … just as we would with other forms of pulmonary fibrosis,” Dr. Newton said, “and to expand our reach to others not sitting in our clinics who have the same rare condition or are at risk.”
After cascade testing, Dr. Garcia said, she invites family members with positive results to have baseline CT scans and pulmonary function testing. “And if there’s anything abnormal, we’re inviting them to have regular follow-up testing,” she said, “because we advise starting antifibrotic treatment at the very first sign of disease worsening.”
Such an approach to genetic testing for patients and relatives is described in a statement commissioned by the Pulmonary Fibrosis Foundation and published last year in the journal Chest (2022:162[2]:394-405). The statement, for which Dr. Newton and Dr. Garcia were among the authors, also lists clinical features within patients and families suggestive of a possible genetic pathway, and describes the potential yield for identifying a variant in different clinical scenarios.
Pathogenic variants in telomere genes as well as findings of short telomere length are associated with various extrapulmonary manifestations such as liver dysfunction, bone marrow dysfunction, and head and neck cancers, Dr. Newton said, making surveillance and referrals important. (Rare variants and short telomere length are associated with disease progression across several non-IPF diagnoses as well.)
Moreover, short telomeres may signal the need to avoid long-term immunosuppression. Research published in 2019 from multiple cohorts, and led by Dr. Newton and Dr. Garcia, showed that short telomere length is associated with worse outcomes (faster time to composite death, transplant, FVC decline, and hospitalization) in patients with IPF who received immunosuppression. These adverse outcomes were not found in IPF patients with normal telomere lengths who received similar immunosuppression (Am J Respir Crit Care Med. 2019;200(3):336-347).
Gene sequencing and telomere length measurement are described in the 2020 Chest statement on the role of genetic testing in PF as yielding “different yet complementary information.” Short age-adjusted telomere length (less than the 10th percentile) is common in those with pathogenic variants in telomere genes, but it can also occur in the absence of identifiable rare telomere-related variants, the statement says. Telomere length testing can be helpful, it notes, in determining the significance of a “variant of unknown significance (VUS)” if gene sequencing identifies one.
The future of genetic screening for PF
Future genetic screening approaches for PF may cast an even wider net while better stratifying risk for family members. At Brigham and Women’s Hospital, where family screening was a major impetus for the 2008 founding of the Pulmonary Genetics Center, research published several years ago by Dr. Raby and his colleagues found that 31% of 107 asymptomatic first-degree relatives of patients with PF had interstitial lung abnormalities on chest CTs – whether or not a family history was reported – and 18% had clear radiographic or physiological manifestations of fibrosis (Am J Respir Crit Care Med. 2020;201[10]:1240-8).
“That’s more than 10-fold higher than what we thought we’d see, based on prior literature. … And the numbers were pretty much the same whether or not there was a family history of fibrosis reported by the patient,” said Dr. Raby, also the Leila and Irving Perlmutter professor of pediatrics at Harvard Medical School, Boston, and chief of the division of pulmonary medicine at Boston Children’s Hospital. “We used to think we only needed to worry about genetic risk when there was a family history. But now we see that sporadic cases are also driven by genetics.”
Their study also included a 2-year follow-up chest CT, in which the majority of the screened relatives participated. Of those, 65% who had interstitial changes at baseline showed progression. Four percent of those without interstitial abnormalities at baseline developed abnormalities (Am J Respir Crit Care Med. 2023;207[2]:211-4). “The fact that 65% progressed suggests that in the majority of patients what we’re finding is something that’s real and is going to be clinically meaningful for patients,” he said.
Genetic signatures
A next phase of research at Brigham & Women’s and Boston Children’s, he said, will address PF’s “complex genetic signature” and test polygenic risk scores for idiopathic PF that take into account not only rare genetic variants that can be solidly linked to disease but many common genetic variants being detected in genome-wide association studies. [By definition, common variants, otherwise known as single-nucleotide polymorphisms (SNPs) occur with greater frequency in the general population (> 5%), generally reside within noncoding regions, and may contribute to disease risk but alone do not cause disease.]
“As technologies and genetic studies improve, we’re seeing we can estimate much better the likelihood of disease than we could 10 years ago,” he said. A “potent” common variant called the MUC5B promoter polymorphism has been shown to confer a 3-fold to 20-fold increased risk for PF, he noted. (Polygenic risk scores are also being developed, he said, for asthma and chronic obstructive pulmonary disease.)
“Every time one sees a patient with PF that is thought to be idiopathic one should start thinking about their at-risk family members, particularly their siblings,” Dr. Raby said. But in doing so, “wouldn’t it be wonderful if we could use polygenic risk scores to assure some [family members] that they’re in the lowest tier of risk and might need pulmonary function studies every 5 years, for example, versus someone we’d want to see more frequently, versus someone [for whom] we’d want to start preventive therapy at the earlier signs of declining lung function?”
Moving forward, he and the others said, the field needs more research to determine how genetic risk factors predict disease progression and prospective clinical trials to test whether long-term outcomes are indeed improved by early institution of antifibrotic therapy and other genetics-driven management decisions. “The data we’re using to inform prognosis and treatment decisions are compelling, but a lot of it is based on cohort studies and retrospective research,” Dr. Newton said.
Multi-institutional transomics studies and other research projects are underway, meanwhile, to build upon gene identifications and learn more about the pathobiology of PF. “We know about two big genetic pathways … but we need to sort it all out,” he said. For instance, “are there intermediate pathways? And where does it actually start? What kind of cell?”
Genetics’ impact on PCD
About 20 years ago, only two genes were linked to PCD, a largely autosomal recessive disorder that results from abnormalities in the cilia and subsequently improper airway clearance. Today, said Dr. Ferkol, there are over 50 known genes that, if defective, can lead to PCD.
“Based on our latest estimates, I’d say we can diagnose people using genetics about 70%, maybe 80%, of the time,” Dr. Ferkol said. Genetic testing has become a first-line diagnostic tool for PCD in North America – a significant development given that a definitive diagnosis has long been challenging, he said.
A genetics-based diagnosis of PCD is sometimes challenged by the finding of variants of unknown significance (VUSs) on genetic testing (often missense mutations) “because some of the genes involved are huge,” noted Dr. Ferkol, who coleads the NIH-funded Genetic Disorders of Mucociliary Clearance Consortium. “But many times, it’s straightforward.”
Children with PCD have repeated or persistent upper respiratory tract infections beginning early in life – like chronic rhinosinusitis or suppurative otitis media – and chronic bronchitis, leading to bronchiectasis. About half of patients have a spectrum of laterality defects, where organs are malpositioned in a mirror image of normal. Some individuals also have cardiac defects, and subfertility in both males and females can frequently occur.
Just as it has become increasingly clear that CF exists as a continuum, with milder and variant forms having been recognized since the advent of genetic testing, “we’re finding genotype-phenotype relationships in PCD,” Dr. Ferkol said. “Certain individuals have more rapid pulmonary decline, which is related in part to their genetics.”
With PCD, “I’m convinced this is a continuum. Some patients have unmistakable, clear-cut PCD, but I’m sure we’re going to find individuals who have milder variants in these PCD-associated genes that lead to milder disease,” he said.
There are no specific treatments that will correct cilia dysfunction, and current therapy options are borrowed from other diseases such as asthma and CF. However, newer treatments targeting specific genetic defects are in early clinical studies. Will the gene discoveries and more research open up new avenues for treating PCD, as happened in CF? Dr. Ferkol hopes so.
Approximately 2,000 genetic variants have been identified in the CFTR gene, though not all are pathogenic. “The newer, highly effective modulators used in CF target a particular CFTR mutation class, so some drugs will work for some people with the disease, but not all,” Dr. Ferkol said. “It’s personalized medicine.”
Modulator therapies designed to correct the malfunctioning proteins made by the CFTR gene have profoundly changed the lives of many with CF, improving lung function and everyday symptoms for patients, allowing them to lead near-normal lives. “It’s astonishing,” he said.
Dr. Garcia reported consulting for Rejuvenation Technologies and Rejuveron Telomere Therapeutics; in addition, her laboratory has received support from Boehringer Ingelheim and Astrazeneca for investigator-initiated research. Dr. Newton reported he has performed consulting for Boehringer Ingelheim. Dr. Ferkol reported involvement in a longitudinal study defining endpoints for future clinical PCD trials funded by ReCode Therapeutics and leadership of an international clinical trial for PCD supported by Parion Sciences. He has received honoraria from the Cystic Fibrosis Foundation and serves as a member of the ReCode Therapeutics PCD Clinical Steering Committee. Dr. Raby reported no relevant disclosures.
The remarkable story of cystic fibrosis (CF) – from gene discovery in 1989 to highly effective precision-medicine therapies today – inspires Christine Kim Garcia, MD, PhD, as she searches for rare mutations in genes linked to inherited forms of lung fibrosis, termed familial pulmonary fibrosis (FPF).
“Cystic fibrosis has provided a framework for approaching the genetics of lung fibrosis,” said Dr. Garcia, Frode Jensen Professor of Medicine and chief of the pulmonology, allergy, and critical care medicine division at Columbia University, and director of the Columbia Precision Medicine Initiative, both in New York.
Pulmonary fibrosis is more complicated than CF. “Mutations in more than 10 different genes can lead to the increased heritable risk of pulmonary fibrosis that we find in families. Different mutations exist for each gene. Sometimes the mutations are so rare that they are only found in a single family,” she said. “In addition, different subtypes of fibrotic interstitial lung disease can be linked to the same mutation and found in the same family.”
Despite these complexities, genetic discoveries in PF have illuminated pathophysiologic pathways and are driving the research that Dr. Garcia and other experts hope will lead to helpful prognostic tools and to precision therapies. And already, at institutions like Columbia, genetic discoveries are changing clinical care, driving treatment decisions and spurring family screening.
Thomas Ferkol, MD, whose research focuses on genetic factors that contribute to suppurative airway diseases such as CF and primary ciliary dyskinesia (PCD), similarly regards CF as a road map for genetics research and genetic testing in practice.
“The treatments we’re doing now for CF are increasingly based on the genetics of the individual,” said Dr. Ferkol, professor and division chief for pediatric pulmonology at the University of North Carolina at Chapel Hill, where the UNC Children’s Hospital hosts a rare and genetic lung disease program. For PCD, genetic testing has become a front-line diagnostic tool. But in the future, he hopes, it will also become a determinant for personalized treatment for children with PCD.
The cystic fibrosis transmembrane conductance regulator (CFTR) gene was the first lung disease gene to be discovered using gene-mapping techniques. Since then, and especially in the last 15-20 years, “there’s been a lot of progress in the identification of genes for which mutations and variations cause specific forms of pulmonary disease, many of which can now establish a firm diagnosis, and some of which lead to very directed changes in management. There has also been great progress in the availability of genetic testing,” said Benjamin A. Raby, MD, MPH, director of the Pulmonary Genetics Center at Brigham and Women’s Hospital, Boston, which sees patients with a host of cystic lung diseases, bronchiectasic lung diseases, fibrotic lung diseases, and other conditions, including pulmonary fibrosis and PCD.
Pulmonary fibrosis in adults and PCD in children are two examples of lung diseases for which genetic discoveries have exploded in recent years, with important implications for care now and in the future.
Leveraging genetic testing in PF
FPF describes families with two or more members with PF within three degrees of relationship; it is a designation believed to affect 20%-25% of people with PF and occurs predominantly later in the adult years (after 50 years of age), most commonly in autosomal dominant fashion, and amidst a stew of genetic risks, environmental exposures, and other insults.
Dr. Garcia and other researchers have uncovered two main types of genes in which rare variants can give rise to a heritable risk of FP: Genes that contribute to the maintenance of telomere length, and genes involved in surfactant metabolism. [Last year, Dr. Garcia and colleagues reported their discovery of both rare and common variants in a “spindle gene,” KIF15, in patients with IPF, suggesting an additional pathogenic pathway. The gene controls dynamics of cell division. (Am J Respir Crit Care Med. 2022;206[1]:p 56-69.)]
Detection of telomere pathway involvement – most commonly involving the TERT gene – is consequential because patients with telomere-associated gene mutations “tend to progress faster and have a more aggressive disease course than patients without these mutations … regardless of how their scans or biopsies look,” as do patients who have short age-adjusted telomere length, said Dr. Chad Newton, MD, who directs the Interstitial Lung Disease program at the University of Texas Southwestern and researches the genetics of ILD.
Dr. Newton and Dr. Garcia advise patients with PF and a positive family history to undergo panel-based genetic sequencing, along with telomere length measurement. They also advise that undiagnosed first-degree relatives consider what’s called “cascade testing” – genetic sequencing for any pathogenic or likely pathogenic rare variants found in the patient’s investigation. (Dr. Garcia, who cochairs a National Institutes of Health–funded interstitial lung disease curation panel, said she finds evidence of a pathogenic or likely pathogenic variant in about 25% of patients with a family history of PF.)
“We can use this genetic information to consider starting early [antifibrotic] treatment to try to delay progression … just as we would with other forms of pulmonary fibrosis,” Dr. Newton said, “and to expand our reach to others not sitting in our clinics who have the same rare condition or are at risk.”
After cascade testing, Dr. Garcia said, she invites family members with positive results to have baseline CT scans and pulmonary function testing. “And if there’s anything abnormal, we’re inviting them to have regular follow-up testing,” she said, “because we advise starting antifibrotic treatment at the very first sign of disease worsening.”
Such an approach to genetic testing for patients and relatives is described in a statement commissioned by the Pulmonary Fibrosis Foundation and published last year in the journal Chest (2022:162[2]:394-405). The statement, for which Dr. Newton and Dr. Garcia were among the authors, also lists clinical features within patients and families suggestive of a possible genetic pathway, and describes the potential yield for identifying a variant in different clinical scenarios.
Pathogenic variants in telomere genes as well as findings of short telomere length are associated with various extrapulmonary manifestations such as liver dysfunction, bone marrow dysfunction, and head and neck cancers, Dr. Newton said, making surveillance and referrals important. (Rare variants and short telomere length are associated with disease progression across several non-IPF diagnoses as well.)
Moreover, short telomeres may signal the need to avoid long-term immunosuppression. Research published in 2019 from multiple cohorts, and led by Dr. Newton and Dr. Garcia, showed that short telomere length is associated with worse outcomes (faster time to composite death, transplant, FVC decline, and hospitalization) in patients with IPF who received immunosuppression. These adverse outcomes were not found in IPF patients with normal telomere lengths who received similar immunosuppression (Am J Respir Crit Care Med. 2019;200(3):336-347).
Gene sequencing and telomere length measurement are described in the 2020 Chest statement on the role of genetic testing in PF as yielding “different yet complementary information.” Short age-adjusted telomere length (less than the 10th percentile) is common in those with pathogenic variants in telomere genes, but it can also occur in the absence of identifiable rare telomere-related variants, the statement says. Telomere length testing can be helpful, it notes, in determining the significance of a “variant of unknown significance (VUS)” if gene sequencing identifies one.
The future of genetic screening for PF
Future genetic screening approaches for PF may cast an even wider net while better stratifying risk for family members. At Brigham and Women’s Hospital, where family screening was a major impetus for the 2008 founding of the Pulmonary Genetics Center, research published several years ago by Dr. Raby and his colleagues found that 31% of 107 asymptomatic first-degree relatives of patients with PF had interstitial lung abnormalities on chest CTs – whether or not a family history was reported – and 18% had clear radiographic or physiological manifestations of fibrosis (Am J Respir Crit Care Med. 2020;201[10]:1240-8).
“That’s more than 10-fold higher than what we thought we’d see, based on prior literature. … And the numbers were pretty much the same whether or not there was a family history of fibrosis reported by the patient,” said Dr. Raby, also the Leila and Irving Perlmutter professor of pediatrics at Harvard Medical School, Boston, and chief of the division of pulmonary medicine at Boston Children’s Hospital. “We used to think we only needed to worry about genetic risk when there was a family history. But now we see that sporadic cases are also driven by genetics.”
Their study also included a 2-year follow-up chest CT, in which the majority of the screened relatives participated. Of those, 65% who had interstitial changes at baseline showed progression. Four percent of those without interstitial abnormalities at baseline developed abnormalities (Am J Respir Crit Care Med. 2023;207[2]:211-4). “The fact that 65% progressed suggests that in the majority of patients what we’re finding is something that’s real and is going to be clinically meaningful for patients,” he said.
Genetic signatures
A next phase of research at Brigham & Women’s and Boston Children’s, he said, will address PF’s “complex genetic signature” and test polygenic risk scores for idiopathic PF that take into account not only rare genetic variants that can be solidly linked to disease but many common genetic variants being detected in genome-wide association studies. [By definition, common variants, otherwise known as single-nucleotide polymorphisms (SNPs) occur with greater frequency in the general population (> 5%), generally reside within noncoding regions, and may contribute to disease risk but alone do not cause disease.]
“As technologies and genetic studies improve, we’re seeing we can estimate much better the likelihood of disease than we could 10 years ago,” he said. A “potent” common variant called the MUC5B promoter polymorphism has been shown to confer a 3-fold to 20-fold increased risk for PF, he noted. (Polygenic risk scores are also being developed, he said, for asthma and chronic obstructive pulmonary disease.)
“Every time one sees a patient with PF that is thought to be idiopathic one should start thinking about their at-risk family members, particularly their siblings,” Dr. Raby said. But in doing so, “wouldn’t it be wonderful if we could use polygenic risk scores to assure some [family members] that they’re in the lowest tier of risk and might need pulmonary function studies every 5 years, for example, versus someone we’d want to see more frequently, versus someone [for whom] we’d want to start preventive therapy at the earlier signs of declining lung function?”
Moving forward, he and the others said, the field needs more research to determine how genetic risk factors predict disease progression and prospective clinical trials to test whether long-term outcomes are indeed improved by early institution of antifibrotic therapy and other genetics-driven management decisions. “The data we’re using to inform prognosis and treatment decisions are compelling, but a lot of it is based on cohort studies and retrospective research,” Dr. Newton said.
Multi-institutional transomics studies and other research projects are underway, meanwhile, to build upon gene identifications and learn more about the pathobiology of PF. “We know about two big genetic pathways … but we need to sort it all out,” he said. For instance, “are there intermediate pathways? And where does it actually start? What kind of cell?”
Genetics’ impact on PCD
About 20 years ago, only two genes were linked to PCD, a largely autosomal recessive disorder that results from abnormalities in the cilia and subsequently improper airway clearance. Today, said Dr. Ferkol, there are over 50 known genes that, if defective, can lead to PCD.
“Based on our latest estimates, I’d say we can diagnose people using genetics about 70%, maybe 80%, of the time,” Dr. Ferkol said. Genetic testing has become a first-line diagnostic tool for PCD in North America – a significant development given that a definitive diagnosis has long been challenging, he said.
A genetics-based diagnosis of PCD is sometimes challenged by the finding of variants of unknown significance (VUSs) on genetic testing (often missense mutations) “because some of the genes involved are huge,” noted Dr. Ferkol, who coleads the NIH-funded Genetic Disorders of Mucociliary Clearance Consortium. “But many times, it’s straightforward.”
Children with PCD have repeated or persistent upper respiratory tract infections beginning early in life – like chronic rhinosinusitis or suppurative otitis media – and chronic bronchitis, leading to bronchiectasis. About half of patients have a spectrum of laterality defects, where organs are malpositioned in a mirror image of normal. Some individuals also have cardiac defects, and subfertility in both males and females can frequently occur.
Just as it has become increasingly clear that CF exists as a continuum, with milder and variant forms having been recognized since the advent of genetic testing, “we’re finding genotype-phenotype relationships in PCD,” Dr. Ferkol said. “Certain individuals have more rapid pulmonary decline, which is related in part to their genetics.”
With PCD, “I’m convinced this is a continuum. Some patients have unmistakable, clear-cut PCD, but I’m sure we’re going to find individuals who have milder variants in these PCD-associated genes that lead to milder disease,” he said.
There are no specific treatments that will correct cilia dysfunction, and current therapy options are borrowed from other diseases such as asthma and CF. However, newer treatments targeting specific genetic defects are in early clinical studies. Will the gene discoveries and more research open up new avenues for treating PCD, as happened in CF? Dr. Ferkol hopes so.
Approximately 2,000 genetic variants have been identified in the CFTR gene, though not all are pathogenic. “The newer, highly effective modulators used in CF target a particular CFTR mutation class, so some drugs will work for some people with the disease, but not all,” Dr. Ferkol said. “It’s personalized medicine.”
Modulator therapies designed to correct the malfunctioning proteins made by the CFTR gene have profoundly changed the lives of many with CF, improving lung function and everyday symptoms for patients, allowing them to lead near-normal lives. “It’s astonishing,” he said.
Dr. Garcia reported consulting for Rejuvenation Technologies and Rejuveron Telomere Therapeutics; in addition, her laboratory has received support from Boehringer Ingelheim and Astrazeneca for investigator-initiated research. Dr. Newton reported he has performed consulting for Boehringer Ingelheim. Dr. Ferkol reported involvement in a longitudinal study defining endpoints for future clinical PCD trials funded by ReCode Therapeutics and leadership of an international clinical trial for PCD supported by Parion Sciences. He has received honoraria from the Cystic Fibrosis Foundation and serves as a member of the ReCode Therapeutics PCD Clinical Steering Committee. Dr. Raby reported no relevant disclosures.
PCPs prep for ‘less predictable’ respiratory virus season
Hospitalizations for COVID-19 in the United States have increased for 8 weeks in a row.
Data from Florida and Georgia signal that respiratory syncytial virus (RSV) season has begun.
As for flu shots, experts say patients with long COVID should get them in 2023, although federal health agencies have not addressed that specific question.
Paul G. Auwaerter, MD, MBA, an infectious disease consultant, said many patients in his primary care practice worry about “the big three” – COVID, influenza, and RSV.
They discussed how to handle COVID boosters, the use of Paxlovid, vaccine hesitancy, and the correct order of operations for patients getting vaccinated against all three diseases.
Paul G. Auwaerter, MD, MBA, clinical director of the division of infectious diseases and the Sherrilyn and Ken Fisher Professor of Medicine at Johns Hopkins University, BaltimoreQuestion: How should primary care physicians be preparing to handle what everyone is predicting will be a major surge in cases of respiratory infections?
Auwaerter: Although I’m an infectious disease consultant, I still have a small primary care practice. So, I field questions for my patients all the time, and many patients, especially those with health problems, are worried about the big three: RSV, COVID, and influenza – at least, my more motivated patients are.
People frequently ask if they need the COVID booster. I think that’s been something many people think maybe they can avoid. The good news is that the early in vitro data suggest that the XBB1.5x-based vaccine seems to offer sufficient neutralizing activity against the circulating newer variants since the vaccine was approved earlier this year. I am suggesting that everyone get a booster, especially those at high risk, because we know that the risk for hospitalization decreases based on earlier studies for 4-6 months after a COVID booster. We can simultaneously administer the revised COVID booster vaccine and the annual influenza vaccine. The timing is good, as influenza immunization should be accomplished by October or early November at the latest. Like many parts of the country, we in Maryland are in the middle of a COVID boomlet. I have issued more Paxlovid prescriptions since mid-August than I did all spring and early summer.
Q: Are you seeing a lot of rebound COVID in your patients taking Paxlovid [nirmatrelvir/ritonavir]?
Dr. Auwaerter: I think the frequency is probably around 10%. It has been quoted much higher – at 20% – but careful studies have put it down at just single digits. I think it just depends on symptomatology and how you ask the question. But I think it’s important that I try to persuade people to take a direct-acting antiviral if they’re in a high-risk category rather than tough it out. Increasing data suggest taking an antiviral also reduces the risk for long COVID. Also, we know that rebound symptoms are not always infectious virus. Sometimes, they’re just inflammatory. Unless a person is immune suppressed, they rarely have a culturable virus 7-8 days after onset of symptoms. So, for most people, I don’t administer second courses of Paxlovid, although I know some physicians do. One has to realize the risk for hospitalization from a rebound is tiny, and many people don’t even have infectious virus when they take the second course of a drug such as Paxlovid.
Q: You mentioned motivated patients, which seems to be an important factor to consider, particularly for new vaccines.
Dr. Auwaerter: There are always early adopters who are less afraid. And then some people say: This is a brand-new vaccine; I’m going to wait for a year to let this shake out, and make sure it seems safe. People more engaged in their health have asked me about the RSV vaccine. For anyone who has cardiopulmonary problems and other major health problems, I’ve advised it. But if someone’s in good health and 65 or 70, the RSV illness is probably pretty mild if they get it. For them, I would say the vaccine is optional.
For people over 75, I have been advising the RSV vaccine because that is a group we tend to see hospitalized with RSV; they’re the highest-risk group, similar to COVID. The older you are, the more likely this infection will land you in the hospital. You can acquire RSV even if you don’t have young grandchildren around.
Q: You have called respiratory virus seasons unstable? What does it mean, and what is the significance for clinicians?
Dr. Auwaerter: It’s less predictable than in the past. If you had a cough and fever, you could think it was influenza if you knew you had influenza circulating in your community. Maybe you thought about RSV for your immunocompromised or older patients, but we didn’t have any therapy for it anyway. I sometimes refer to the respiratory virus season as a cage match between the major infections. Last year, RSV came out first, and we got some influenza and COVID. What does the situation look like this year? I don’t know at this point, but we are seeing more COVID earlier. What’s different is we continue to have the emergence of viral variants of SARS-CoV-2. Also, with both influenza and COVID, it’s harder to make a clinical judgment about what people have.
I think we have to rely more on tests to treat these patients. Options include having point of care testing in the office for rapid results (molecular assays preferred) for both influenza and SARS-CoV-2 or home antigen testing. There are home kits that do test for both if influenza is known to be circulating significantly in the community. But there are still barriers. For one, COVID and COVID/influenza antigen kits are no longer free, although some health insurance companies do provide COVID kits free of charge. In offices, you don’t want to have ill people with respiratory infections in your waiting room unless you can isolate or have negative pressure rooms. Do you ask for masking in your offices? Telemedicine has been a big help since the pandemic in managing nonsevere respiratory infections at home; however, you must be licensed in the state to practice, which limits helping your out-of-state patients.
Q: How has the advent of in-home antigen tests changed practice?
Dr. Auwaerter: Home antigen tests have been groundbreaking in facilitating care. When I see patients via telemedicine, I don’t want to prescribe medications for influenza and COVID to people simultaneously. I want to pick one or the other – and now I’m able to ask for a COVID test or a COVID/influenza test if the patient or family is able to get a kit. Some offices do have real-time molecular testing, which is the ideal and the CDC-recommended approach, but they’re expensive, and not everyone has access to them.
Q: People talk about the “tripledemic,” but does doing so ignore the fourth horseman of the respiratory apocalypse: pneumococcal pneumonia?
Dr. Auwaerter: Pneumonia remains a leading cause of hospitalization, except we’ve seen much more viral than bacterial pneumonia in recent years of the pandemic. We’ve lost sight, and pneumococcal pneumonia is important, especially in older patients. What we have seen pretty clearly is a rise in group A streptococcal infections. This is another consequence of the pandemic, where people did not socialize for a year or 2. There was much less group A strep infection in younger children, and even in adults, the amount of invasive group A streptococcal infections has clearly taken a jump, according to the NHS in Great Britain. Our pediatric practices here at Johns Hopkins are seeing far more cases of acute rheumatic fever than they’ve seen in decades. And I think, again, this is a consequence of the frequency of group A strep infections definitely taking an uptick. And that was no doubt probably from social mitigation measures and just an interruption in normal circumstances that bacterial and respiratory pathogens tend to circulate and colonize.
Q: Do you have any concerns about immunogenicity or side effects associated with receiving several vaccines at once?
Dr. Auwaerter: I think three injections at once is only for the heroic, and there is actually no guidance for getting all three at the moment. COVID, RSV, and influenza are not live vaccines. I’ve been recommending the new COVID booster and flu together, and then wait 2 weeks and then get RSV or vice-versa. A part of the reason is RSV is new. People have gotten COVID and flu vaccines before; they’re no different than in the past in terms of anticipating adverse effects. But RSV is new, so I’ve usually been recommending that as a standalone to gauge if there are issues as an RSV booster may be recommended at some point down the road.
Q: Unfortunately, some people are going to see or hear misinformation that the COVID boosters have not been properly tested or proven safe. What’s your response to the patient who says something to that effect?
Dr. Auwaerter: My response is, the basic components of the vaccine are the same, right? If you have the mRNA vaccine, you’re getting the vaccine components, the lipids, and the mRNA coding for spike proteins, which has just been modified slightly to adjust to the Omicron subvariant composition. We do the same thing with the influenza vaccine every year, and we don’t see much change in the side effect profile. I think it’s important for my staff in the office and myself to be very comfortable to field questions such as these.
We try to inform all of our staff about a vaccine, especially a new one like RSV, just so they have some comfort level with it, whether they’re getting it or not. Vaccine-hesitant patients need very little to dissuade and to take a pass – to the probable detriment of their health and their family’s health. We know the influenza vaccine helps reduce absenteeism and transmission in addition to reducing serious illness in high-risk patients. Even COVID vaccine efficacy is not as robust as initially reported, falling from 95% to under 70% depending on the study – you are provided with protection against serious illness and hospitalization. The same goes for influenza, and that’s how we try to pitch it to people. Are they going to get the flu? Maybe, but you didn’t land in the hospital. That’s why it’s these vaccines are so important.
Spencer H. Durham, PharmD, associate clinical professor in the department of pharmacy practice at Auburn (Ala.) University, and clinical pharmacist, Internal Medicine & Infectious Diseases, at the UAB Heersink School of Medicine in Huntsville.Q: What is known, if anything, about the risks/desirability of giving three vaccinations at once to patients (particularly older patients) – flu, COVID-19 and RSV? Any potential vaccine interactions physicians should know about?
Dr. Durham: There are currently no data about giving all three of these vaccines together at the same time. However, there is both data and practical experience of giving both the flu and COVID vaccines at the same time. The best approach right now for these three vaccines would be to get the flu and COVID vaccines at the same time, then give the RSV vaccine at a different date. In general, they should be separated by about 2 weeks, although it does not matter in what order they are given (that is, patients could get RSV first, then flu/COVID, or they could get flu/COVID first, followed by RSV).
Having said this, there is no theoretical reason why patients couldn’t get all three at once, so if there is only one opportunity to vaccinate a patient, then it would be okay to give all three. But, if the patient can come for two separate visits, the recommendation would currently be to separate these. In the future, there likely will be data on giving all three vaccines at once, so it may not be an issue to administer all three at the same time.
Lastly, I would point out that the RSV vaccine is not necessarily recommended for everyone age 60 and above. The Advisory Committee on Immunization Practices recommends using shared clinical decision-making to determine if that vaccine is right for the patient. In general, the flu and COVID vaccines are recommended for everyone, although the specific COVID recommendations for fall 2023 have not yet been released. There are no particular vaccine interactions that are concerning with these vaccines.
Q: What if any special considerations are there regarding the storage, handling, and ordering of these vaccines? Should primary care practices take any special steps they might not already be taking?
Dr. Durham: I don’t think there are any special considerations that providers might not already be doing. All of the vaccines do require refrigeration, but each individual product may vary some on beyond-use dates or how long they are good after being reconstituted. All providers administering these vaccines should carefully examine the labeling of each individual product to ensure correct storage and handling. In addition, the Centers for Disease Control and Prevention has an online toolkit for vaccine storage and handling and can be found at https://www.cdc.gov/vaccines/hcp/admin/storage/toolkit/index.html.
Santina J. G. Wheat, MD, MPH, vice chair of diversity, equity, and inclusion, department of family and community medicine, and associate professor of family and community medicine, Northwestern University, ChicagoQ: What can primary care doctors/family physicians and their staff do to increase patient access to the vaccines? Any lessons learned from the earlier phases of the pandemic that might pertain not only to COVID-19 but also to RSV and/or influenza?
Dr. Wheat: I think the most important thing family physicians can do is speak with their patients about the importance of vaccines and specific recommendations they have for the situations of individuals and families. When vaccines started becoming available, I had many patients who wanted to hear from me – as their primary physician – what I truly thought and what I was planning to do for my own family.
I also think if our teams can know where vaccines are easily accessible, that makes it much easier for our patients. I have heard great stories and seen my own clinical support staff look at websites with patients to help them find the best location to get vaccines. In particular, about the RSV vaccine, I have had a handful of patients already come to ask me about my recommendations. When vaccines are available at my location, I find it much easier for my patients to be willing to get vaccinated. Similarly, if I am sending patients to pick up a prescription and they can get it at the same time, I have found success in them being willing to be vaccinated while picking up their prescription. In both instances, they do not need to make an additional stop; they are just able to be vaccinated while already at the clinic or pharmacy.
Q: Do you see any extra difficulties involved in trying to get groups of patients – in this case, older people – to be receptive to three vaccines, especially in this climate where it appears a growing number of people are hostile to immunization?
Dr. Wheat: Recently, I have found myself negotiating vaccines with patients not just with these, but as recommendations have changed for vaccines such as the pneumococcal vaccines and the hepatitis B vaccines. I think primary care providers can recommend all of them, but still help patients prioritize what is most important for that patient and family. For example, if welcoming a new baby soon, they might prioritize the vaccines for pertussis or influenza over the hepatitis vaccine with a plan to revisit the conversations later.
I have had some patients tell me they have gotten enough vaccines – and we know that even before the pandemic there was resistance to the influenza vaccine for some. I think we need to be prepared to address the concerns and, at times, the apathy. We also need to ask every time, because we never know which visit will be the one when a patient agrees.
Dr. Auwaerter reported financial relationships with Pfizer, Shionogi, Gilead, and Wellstat. Dr. Durham and Dr. Wheat disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Hospitalizations for COVID-19 in the United States have increased for 8 weeks in a row.
Data from Florida and Georgia signal that respiratory syncytial virus (RSV) season has begun.
As for flu shots, experts say patients with long COVID should get them in 2023, although federal health agencies have not addressed that specific question.
Paul G. Auwaerter, MD, MBA, an infectious disease consultant, said many patients in his primary care practice worry about “the big three” – COVID, influenza, and RSV.
They discussed how to handle COVID boosters, the use of Paxlovid, vaccine hesitancy, and the correct order of operations for patients getting vaccinated against all three diseases.
Paul G. Auwaerter, MD, MBA, clinical director of the division of infectious diseases and the Sherrilyn and Ken Fisher Professor of Medicine at Johns Hopkins University, BaltimoreQuestion: How should primary care physicians be preparing to handle what everyone is predicting will be a major surge in cases of respiratory infections?
Auwaerter: Although I’m an infectious disease consultant, I still have a small primary care practice. So, I field questions for my patients all the time, and many patients, especially those with health problems, are worried about the big three: RSV, COVID, and influenza – at least, my more motivated patients are.
People frequently ask if they need the COVID booster. I think that’s been something many people think maybe they can avoid. The good news is that the early in vitro data suggest that the XBB1.5x-based vaccine seems to offer sufficient neutralizing activity against the circulating newer variants since the vaccine was approved earlier this year. I am suggesting that everyone get a booster, especially those at high risk, because we know that the risk for hospitalization decreases based on earlier studies for 4-6 months after a COVID booster. We can simultaneously administer the revised COVID booster vaccine and the annual influenza vaccine. The timing is good, as influenza immunization should be accomplished by October or early November at the latest. Like many parts of the country, we in Maryland are in the middle of a COVID boomlet. I have issued more Paxlovid prescriptions since mid-August than I did all spring and early summer.
Q: Are you seeing a lot of rebound COVID in your patients taking Paxlovid [nirmatrelvir/ritonavir]?
Dr. Auwaerter: I think the frequency is probably around 10%. It has been quoted much higher – at 20% – but careful studies have put it down at just single digits. I think it just depends on symptomatology and how you ask the question. But I think it’s important that I try to persuade people to take a direct-acting antiviral if they’re in a high-risk category rather than tough it out. Increasing data suggest taking an antiviral also reduces the risk for long COVID. Also, we know that rebound symptoms are not always infectious virus. Sometimes, they’re just inflammatory. Unless a person is immune suppressed, they rarely have a culturable virus 7-8 days after onset of symptoms. So, for most people, I don’t administer second courses of Paxlovid, although I know some physicians do. One has to realize the risk for hospitalization from a rebound is tiny, and many people don’t even have infectious virus when they take the second course of a drug such as Paxlovid.
Q: You mentioned motivated patients, which seems to be an important factor to consider, particularly for new vaccines.
Dr. Auwaerter: There are always early adopters who are less afraid. And then some people say: This is a brand-new vaccine; I’m going to wait for a year to let this shake out, and make sure it seems safe. People more engaged in their health have asked me about the RSV vaccine. For anyone who has cardiopulmonary problems and other major health problems, I’ve advised it. But if someone’s in good health and 65 or 70, the RSV illness is probably pretty mild if they get it. For them, I would say the vaccine is optional.
For people over 75, I have been advising the RSV vaccine because that is a group we tend to see hospitalized with RSV; they’re the highest-risk group, similar to COVID. The older you are, the more likely this infection will land you in the hospital. You can acquire RSV even if you don’t have young grandchildren around.
Q: You have called respiratory virus seasons unstable? What does it mean, and what is the significance for clinicians?
Dr. Auwaerter: It’s less predictable than in the past. If you had a cough and fever, you could think it was influenza if you knew you had influenza circulating in your community. Maybe you thought about RSV for your immunocompromised or older patients, but we didn’t have any therapy for it anyway. I sometimes refer to the respiratory virus season as a cage match between the major infections. Last year, RSV came out first, and we got some influenza and COVID. What does the situation look like this year? I don’t know at this point, but we are seeing more COVID earlier. What’s different is we continue to have the emergence of viral variants of SARS-CoV-2. Also, with both influenza and COVID, it’s harder to make a clinical judgment about what people have.
I think we have to rely more on tests to treat these patients. Options include having point of care testing in the office for rapid results (molecular assays preferred) for both influenza and SARS-CoV-2 or home antigen testing. There are home kits that do test for both if influenza is known to be circulating significantly in the community. But there are still barriers. For one, COVID and COVID/influenza antigen kits are no longer free, although some health insurance companies do provide COVID kits free of charge. In offices, you don’t want to have ill people with respiratory infections in your waiting room unless you can isolate or have negative pressure rooms. Do you ask for masking in your offices? Telemedicine has been a big help since the pandemic in managing nonsevere respiratory infections at home; however, you must be licensed in the state to practice, which limits helping your out-of-state patients.
Q: How has the advent of in-home antigen tests changed practice?
Dr. Auwaerter: Home antigen tests have been groundbreaking in facilitating care. When I see patients via telemedicine, I don’t want to prescribe medications for influenza and COVID to people simultaneously. I want to pick one or the other – and now I’m able to ask for a COVID test or a COVID/influenza test if the patient or family is able to get a kit. Some offices do have real-time molecular testing, which is the ideal and the CDC-recommended approach, but they’re expensive, and not everyone has access to them.
Q: People talk about the “tripledemic,” but does doing so ignore the fourth horseman of the respiratory apocalypse: pneumococcal pneumonia?
Dr. Auwaerter: Pneumonia remains a leading cause of hospitalization, except we’ve seen much more viral than bacterial pneumonia in recent years of the pandemic. We’ve lost sight, and pneumococcal pneumonia is important, especially in older patients. What we have seen pretty clearly is a rise in group A streptococcal infections. This is another consequence of the pandemic, where people did not socialize for a year or 2. There was much less group A strep infection in younger children, and even in adults, the amount of invasive group A streptococcal infections has clearly taken a jump, according to the NHS in Great Britain. Our pediatric practices here at Johns Hopkins are seeing far more cases of acute rheumatic fever than they’ve seen in decades. And I think, again, this is a consequence of the frequency of group A strep infections definitely taking an uptick. And that was no doubt probably from social mitigation measures and just an interruption in normal circumstances that bacterial and respiratory pathogens tend to circulate and colonize.
Q: Do you have any concerns about immunogenicity or side effects associated with receiving several vaccines at once?
Dr. Auwaerter: I think three injections at once is only for the heroic, and there is actually no guidance for getting all three at the moment. COVID, RSV, and influenza are not live vaccines. I’ve been recommending the new COVID booster and flu together, and then wait 2 weeks and then get RSV or vice-versa. A part of the reason is RSV is new. People have gotten COVID and flu vaccines before; they’re no different than in the past in terms of anticipating adverse effects. But RSV is new, so I’ve usually been recommending that as a standalone to gauge if there are issues as an RSV booster may be recommended at some point down the road.
Q: Unfortunately, some people are going to see or hear misinformation that the COVID boosters have not been properly tested or proven safe. What’s your response to the patient who says something to that effect?
Dr. Auwaerter: My response is, the basic components of the vaccine are the same, right? If you have the mRNA vaccine, you’re getting the vaccine components, the lipids, and the mRNA coding for spike proteins, which has just been modified slightly to adjust to the Omicron subvariant composition. We do the same thing with the influenza vaccine every year, and we don’t see much change in the side effect profile. I think it’s important for my staff in the office and myself to be very comfortable to field questions such as these.
We try to inform all of our staff about a vaccine, especially a new one like RSV, just so they have some comfort level with it, whether they’re getting it or not. Vaccine-hesitant patients need very little to dissuade and to take a pass – to the probable detriment of their health and their family’s health. We know the influenza vaccine helps reduce absenteeism and transmission in addition to reducing serious illness in high-risk patients. Even COVID vaccine efficacy is not as robust as initially reported, falling from 95% to under 70% depending on the study – you are provided with protection against serious illness and hospitalization. The same goes for influenza, and that’s how we try to pitch it to people. Are they going to get the flu? Maybe, but you didn’t land in the hospital. That’s why it’s these vaccines are so important.
Spencer H. Durham, PharmD, associate clinical professor in the department of pharmacy practice at Auburn (Ala.) University, and clinical pharmacist, Internal Medicine & Infectious Diseases, at the UAB Heersink School of Medicine in Huntsville.Q: What is known, if anything, about the risks/desirability of giving three vaccinations at once to patients (particularly older patients) – flu, COVID-19 and RSV? Any potential vaccine interactions physicians should know about?
Dr. Durham: There are currently no data about giving all three of these vaccines together at the same time. However, there is both data and practical experience of giving both the flu and COVID vaccines at the same time. The best approach right now for these three vaccines would be to get the flu and COVID vaccines at the same time, then give the RSV vaccine at a different date. In general, they should be separated by about 2 weeks, although it does not matter in what order they are given (that is, patients could get RSV first, then flu/COVID, or they could get flu/COVID first, followed by RSV).
Having said this, there is no theoretical reason why patients couldn’t get all three at once, so if there is only one opportunity to vaccinate a patient, then it would be okay to give all three. But, if the patient can come for two separate visits, the recommendation would currently be to separate these. In the future, there likely will be data on giving all three vaccines at once, so it may not be an issue to administer all three at the same time.
Lastly, I would point out that the RSV vaccine is not necessarily recommended for everyone age 60 and above. The Advisory Committee on Immunization Practices recommends using shared clinical decision-making to determine if that vaccine is right for the patient. In general, the flu and COVID vaccines are recommended for everyone, although the specific COVID recommendations for fall 2023 have not yet been released. There are no particular vaccine interactions that are concerning with these vaccines.
Q: What if any special considerations are there regarding the storage, handling, and ordering of these vaccines? Should primary care practices take any special steps they might not already be taking?
Dr. Durham: I don’t think there are any special considerations that providers might not already be doing. All of the vaccines do require refrigeration, but each individual product may vary some on beyond-use dates or how long they are good after being reconstituted. All providers administering these vaccines should carefully examine the labeling of each individual product to ensure correct storage and handling. In addition, the Centers for Disease Control and Prevention has an online toolkit for vaccine storage and handling and can be found at https://www.cdc.gov/vaccines/hcp/admin/storage/toolkit/index.html.
Santina J. G. Wheat, MD, MPH, vice chair of diversity, equity, and inclusion, department of family and community medicine, and associate professor of family and community medicine, Northwestern University, ChicagoQ: What can primary care doctors/family physicians and their staff do to increase patient access to the vaccines? Any lessons learned from the earlier phases of the pandemic that might pertain not only to COVID-19 but also to RSV and/or influenza?
Dr. Wheat: I think the most important thing family physicians can do is speak with their patients about the importance of vaccines and specific recommendations they have for the situations of individuals and families. When vaccines started becoming available, I had many patients who wanted to hear from me – as their primary physician – what I truly thought and what I was planning to do for my own family.
I also think if our teams can know where vaccines are easily accessible, that makes it much easier for our patients. I have heard great stories and seen my own clinical support staff look at websites with patients to help them find the best location to get vaccines. In particular, about the RSV vaccine, I have had a handful of patients already come to ask me about my recommendations. When vaccines are available at my location, I find it much easier for my patients to be willing to get vaccinated. Similarly, if I am sending patients to pick up a prescription and they can get it at the same time, I have found success in them being willing to be vaccinated while picking up their prescription. In both instances, they do not need to make an additional stop; they are just able to be vaccinated while already at the clinic or pharmacy.
Q: Do you see any extra difficulties involved in trying to get groups of patients – in this case, older people – to be receptive to three vaccines, especially in this climate where it appears a growing number of people are hostile to immunization?
Dr. Wheat: Recently, I have found myself negotiating vaccines with patients not just with these, but as recommendations have changed for vaccines such as the pneumococcal vaccines and the hepatitis B vaccines. I think primary care providers can recommend all of them, but still help patients prioritize what is most important for that patient and family. For example, if welcoming a new baby soon, they might prioritize the vaccines for pertussis or influenza over the hepatitis vaccine with a plan to revisit the conversations later.
I have had some patients tell me they have gotten enough vaccines – and we know that even before the pandemic there was resistance to the influenza vaccine for some. I think we need to be prepared to address the concerns and, at times, the apathy. We also need to ask every time, because we never know which visit will be the one when a patient agrees.
Dr. Auwaerter reported financial relationships with Pfizer, Shionogi, Gilead, and Wellstat. Dr. Durham and Dr. Wheat disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Hospitalizations for COVID-19 in the United States have increased for 8 weeks in a row.
Data from Florida and Georgia signal that respiratory syncytial virus (RSV) season has begun.
As for flu shots, experts say patients with long COVID should get them in 2023, although federal health agencies have not addressed that specific question.
Paul G. Auwaerter, MD, MBA, an infectious disease consultant, said many patients in his primary care practice worry about “the big three” – COVID, influenza, and RSV.
They discussed how to handle COVID boosters, the use of Paxlovid, vaccine hesitancy, and the correct order of operations for patients getting vaccinated against all three diseases.
Paul G. Auwaerter, MD, MBA, clinical director of the division of infectious diseases and the Sherrilyn and Ken Fisher Professor of Medicine at Johns Hopkins University, BaltimoreQuestion: How should primary care physicians be preparing to handle what everyone is predicting will be a major surge in cases of respiratory infections?
Auwaerter: Although I’m an infectious disease consultant, I still have a small primary care practice. So, I field questions for my patients all the time, and many patients, especially those with health problems, are worried about the big three: RSV, COVID, and influenza – at least, my more motivated patients are.
People frequently ask if they need the COVID booster. I think that’s been something many people think maybe they can avoid. The good news is that the early in vitro data suggest that the XBB1.5x-based vaccine seems to offer sufficient neutralizing activity against the circulating newer variants since the vaccine was approved earlier this year. I am suggesting that everyone get a booster, especially those at high risk, because we know that the risk for hospitalization decreases based on earlier studies for 4-6 months after a COVID booster. We can simultaneously administer the revised COVID booster vaccine and the annual influenza vaccine. The timing is good, as influenza immunization should be accomplished by October or early November at the latest. Like many parts of the country, we in Maryland are in the middle of a COVID boomlet. I have issued more Paxlovid prescriptions since mid-August than I did all spring and early summer.
Q: Are you seeing a lot of rebound COVID in your patients taking Paxlovid [nirmatrelvir/ritonavir]?
Dr. Auwaerter: I think the frequency is probably around 10%. It has been quoted much higher – at 20% – but careful studies have put it down at just single digits. I think it just depends on symptomatology and how you ask the question. But I think it’s important that I try to persuade people to take a direct-acting antiviral if they’re in a high-risk category rather than tough it out. Increasing data suggest taking an antiviral also reduces the risk for long COVID. Also, we know that rebound symptoms are not always infectious virus. Sometimes, they’re just inflammatory. Unless a person is immune suppressed, they rarely have a culturable virus 7-8 days after onset of symptoms. So, for most people, I don’t administer second courses of Paxlovid, although I know some physicians do. One has to realize the risk for hospitalization from a rebound is tiny, and many people don’t even have infectious virus when they take the second course of a drug such as Paxlovid.
Q: You mentioned motivated patients, which seems to be an important factor to consider, particularly for new vaccines.
Dr. Auwaerter: There are always early adopters who are less afraid. And then some people say: This is a brand-new vaccine; I’m going to wait for a year to let this shake out, and make sure it seems safe. People more engaged in their health have asked me about the RSV vaccine. For anyone who has cardiopulmonary problems and other major health problems, I’ve advised it. But if someone’s in good health and 65 or 70, the RSV illness is probably pretty mild if they get it. For them, I would say the vaccine is optional.
For people over 75, I have been advising the RSV vaccine because that is a group we tend to see hospitalized with RSV; they’re the highest-risk group, similar to COVID. The older you are, the more likely this infection will land you in the hospital. You can acquire RSV even if you don’t have young grandchildren around.
Q: You have called respiratory virus seasons unstable? What does it mean, and what is the significance for clinicians?
Dr. Auwaerter: It’s less predictable than in the past. If you had a cough and fever, you could think it was influenza if you knew you had influenza circulating in your community. Maybe you thought about RSV for your immunocompromised or older patients, but we didn’t have any therapy for it anyway. I sometimes refer to the respiratory virus season as a cage match between the major infections. Last year, RSV came out first, and we got some influenza and COVID. What does the situation look like this year? I don’t know at this point, but we are seeing more COVID earlier. What’s different is we continue to have the emergence of viral variants of SARS-CoV-2. Also, with both influenza and COVID, it’s harder to make a clinical judgment about what people have.
I think we have to rely more on tests to treat these patients. Options include having point of care testing in the office for rapid results (molecular assays preferred) for both influenza and SARS-CoV-2 or home antigen testing. There are home kits that do test for both if influenza is known to be circulating significantly in the community. But there are still barriers. For one, COVID and COVID/influenza antigen kits are no longer free, although some health insurance companies do provide COVID kits free of charge. In offices, you don’t want to have ill people with respiratory infections in your waiting room unless you can isolate or have negative pressure rooms. Do you ask for masking in your offices? Telemedicine has been a big help since the pandemic in managing nonsevere respiratory infections at home; however, you must be licensed in the state to practice, which limits helping your out-of-state patients.
Q: How has the advent of in-home antigen tests changed practice?
Dr. Auwaerter: Home antigen tests have been groundbreaking in facilitating care. When I see patients via telemedicine, I don’t want to prescribe medications for influenza and COVID to people simultaneously. I want to pick one or the other – and now I’m able to ask for a COVID test or a COVID/influenza test if the patient or family is able to get a kit. Some offices do have real-time molecular testing, which is the ideal and the CDC-recommended approach, but they’re expensive, and not everyone has access to them.
Q: People talk about the “tripledemic,” but does doing so ignore the fourth horseman of the respiratory apocalypse: pneumococcal pneumonia?
Dr. Auwaerter: Pneumonia remains a leading cause of hospitalization, except we’ve seen much more viral than bacterial pneumonia in recent years of the pandemic. We’ve lost sight, and pneumococcal pneumonia is important, especially in older patients. What we have seen pretty clearly is a rise in group A streptococcal infections. This is another consequence of the pandemic, where people did not socialize for a year or 2. There was much less group A strep infection in younger children, and even in adults, the amount of invasive group A streptococcal infections has clearly taken a jump, according to the NHS in Great Britain. Our pediatric practices here at Johns Hopkins are seeing far more cases of acute rheumatic fever than they’ve seen in decades. And I think, again, this is a consequence of the frequency of group A strep infections definitely taking an uptick. And that was no doubt probably from social mitigation measures and just an interruption in normal circumstances that bacterial and respiratory pathogens tend to circulate and colonize.
Q: Do you have any concerns about immunogenicity or side effects associated with receiving several vaccines at once?
Dr. Auwaerter: I think three injections at once is only for the heroic, and there is actually no guidance for getting all three at the moment. COVID, RSV, and influenza are not live vaccines. I’ve been recommending the new COVID booster and flu together, and then wait 2 weeks and then get RSV or vice-versa. A part of the reason is RSV is new. People have gotten COVID and flu vaccines before; they’re no different than in the past in terms of anticipating adverse effects. But RSV is new, so I’ve usually been recommending that as a standalone to gauge if there are issues as an RSV booster may be recommended at some point down the road.
Q: Unfortunately, some people are going to see or hear misinformation that the COVID boosters have not been properly tested or proven safe. What’s your response to the patient who says something to that effect?
Dr. Auwaerter: My response is, the basic components of the vaccine are the same, right? If you have the mRNA vaccine, you’re getting the vaccine components, the lipids, and the mRNA coding for spike proteins, which has just been modified slightly to adjust to the Omicron subvariant composition. We do the same thing with the influenza vaccine every year, and we don’t see much change in the side effect profile. I think it’s important for my staff in the office and myself to be very comfortable to field questions such as these.
We try to inform all of our staff about a vaccine, especially a new one like RSV, just so they have some comfort level with it, whether they’re getting it or not. Vaccine-hesitant patients need very little to dissuade and to take a pass – to the probable detriment of their health and their family’s health. We know the influenza vaccine helps reduce absenteeism and transmission in addition to reducing serious illness in high-risk patients. Even COVID vaccine efficacy is not as robust as initially reported, falling from 95% to under 70% depending on the study – you are provided with protection against serious illness and hospitalization. The same goes for influenza, and that’s how we try to pitch it to people. Are they going to get the flu? Maybe, but you didn’t land in the hospital. That’s why it’s these vaccines are so important.
Spencer H. Durham, PharmD, associate clinical professor in the department of pharmacy practice at Auburn (Ala.) University, and clinical pharmacist, Internal Medicine & Infectious Diseases, at the UAB Heersink School of Medicine in Huntsville.Q: What is known, if anything, about the risks/desirability of giving three vaccinations at once to patients (particularly older patients) – flu, COVID-19 and RSV? Any potential vaccine interactions physicians should know about?
Dr. Durham: There are currently no data about giving all three of these vaccines together at the same time. However, there is both data and practical experience of giving both the flu and COVID vaccines at the same time. The best approach right now for these three vaccines would be to get the flu and COVID vaccines at the same time, then give the RSV vaccine at a different date. In general, they should be separated by about 2 weeks, although it does not matter in what order they are given (that is, patients could get RSV first, then flu/COVID, or they could get flu/COVID first, followed by RSV).
Having said this, there is no theoretical reason why patients couldn’t get all three at once, so if there is only one opportunity to vaccinate a patient, then it would be okay to give all three. But, if the patient can come for two separate visits, the recommendation would currently be to separate these. In the future, there likely will be data on giving all three vaccines at once, so it may not be an issue to administer all three at the same time.
Lastly, I would point out that the RSV vaccine is not necessarily recommended for everyone age 60 and above. The Advisory Committee on Immunization Practices recommends using shared clinical decision-making to determine if that vaccine is right for the patient. In general, the flu and COVID vaccines are recommended for everyone, although the specific COVID recommendations for fall 2023 have not yet been released. There are no particular vaccine interactions that are concerning with these vaccines.
Q: What if any special considerations are there regarding the storage, handling, and ordering of these vaccines? Should primary care practices take any special steps they might not already be taking?
Dr. Durham: I don’t think there are any special considerations that providers might not already be doing. All of the vaccines do require refrigeration, but each individual product may vary some on beyond-use dates or how long they are good after being reconstituted. All providers administering these vaccines should carefully examine the labeling of each individual product to ensure correct storage and handling. In addition, the Centers for Disease Control and Prevention has an online toolkit for vaccine storage and handling and can be found at https://www.cdc.gov/vaccines/hcp/admin/storage/toolkit/index.html.
Santina J. G. Wheat, MD, MPH, vice chair of diversity, equity, and inclusion, department of family and community medicine, and associate professor of family and community medicine, Northwestern University, ChicagoQ: What can primary care doctors/family physicians and their staff do to increase patient access to the vaccines? Any lessons learned from the earlier phases of the pandemic that might pertain not only to COVID-19 but also to RSV and/or influenza?
Dr. Wheat: I think the most important thing family physicians can do is speak with their patients about the importance of vaccines and specific recommendations they have for the situations of individuals and families. When vaccines started becoming available, I had many patients who wanted to hear from me – as their primary physician – what I truly thought and what I was planning to do for my own family.
I also think if our teams can know where vaccines are easily accessible, that makes it much easier for our patients. I have heard great stories and seen my own clinical support staff look at websites with patients to help them find the best location to get vaccines. In particular, about the RSV vaccine, I have had a handful of patients already come to ask me about my recommendations. When vaccines are available at my location, I find it much easier for my patients to be willing to get vaccinated. Similarly, if I am sending patients to pick up a prescription and they can get it at the same time, I have found success in them being willing to be vaccinated while picking up their prescription. In both instances, they do not need to make an additional stop; they are just able to be vaccinated while already at the clinic or pharmacy.
Q: Do you see any extra difficulties involved in trying to get groups of patients – in this case, older people – to be receptive to three vaccines, especially in this climate where it appears a growing number of people are hostile to immunization?
Dr. Wheat: Recently, I have found myself negotiating vaccines with patients not just with these, but as recommendations have changed for vaccines such as the pneumococcal vaccines and the hepatitis B vaccines. I think primary care providers can recommend all of them, but still help patients prioritize what is most important for that patient and family. For example, if welcoming a new baby soon, they might prioritize the vaccines for pertussis or influenza over the hepatitis vaccine with a plan to revisit the conversations later.
I have had some patients tell me they have gotten enough vaccines – and we know that even before the pandemic there was resistance to the influenza vaccine for some. I think we need to be prepared to address the concerns and, at times, the apathy. We also need to ask every time, because we never know which visit will be the one when a patient agrees.
Dr. Auwaerter reported financial relationships with Pfizer, Shionogi, Gilead, and Wellstat. Dr. Durham and Dr. Wheat disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.