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The History of Aspirin in Heart Disease Prevention
As the pendulum has swung against recommending aspirin for the primary prevention of heart attacks and strokes, clinicians should focus on other ways to help patients avoid cardiovascular events.
A landmark study published in 1988 in The New England Journal of Medicine reported an astonishing 44% drop in the number of heart attacks among US male physicians aged 40-84 years who took aspirin.
Aspirin subsequently became a daily habit for millions of Americans. In 2017, nearly a quarter of Americans over age 40 who did not have cardiovascular disease (CVD) took the drug, and over 20% of those were doing so without a physician’s recommendation.
But in 2018, three studies (ASCEND, ARRIVE, and ASPREE) showed a stunning reversal in the purported benefit, according to John Wong, MD, vice-chair of the US Preventive Services Task Force (USPSTF).
The calculus for taking aspirin appeared to have changed dramatically: The drug decreased the risk for myocardial infarction by only 11% among study subjects, while its potential harms were much more pronounced.
According to Dr. Wong, who is also a professor of medicine and a primary care physician at Tufts University School of Medicine in Boston, Massachusetts, patients taking low-dose aspirin had a 58% increase in their risk for gastrointestinal bleeding compared with those not on aspirin, as well as a 31% increased risk for intracranial bleeding.
who haven’t had a heart attack or stroke.”
Fewer Americans smoke cigarettes, more realize the benefits of a healthy diet and physical activity, and the medical community better recognizes and treats hypertension. New classes of medications such as statins for high cholesterol are also moving the needle.
But a newer class of drugs may provide a safer replacement for aspirin, according to Muhammad Maqsood, MD, a cardiology fellow at DeBakey Heart and Vascular Center at Methodist Hospital in Houston, Texas. P2Y purinoceptor 12 (P2Y12) inhibitors are effective in lowering the risk for heart attack and stroke in patients with acute coronary syndrome or those undergoing elective percutaneous coronary interventions.
“They have shown a better bleeding profile, especially clopidogrel compared to aspirin,” Dr. Maqsood said.
However, the findings come from trials of patients who already had CVD, so results cannot yet be extrapolated to primary prevention. Dr. Maqsood said the gap highlights the need for clinical trials that evaluate P2Y12 inhibitors for primary prevention, but no such study is registered on clinicaltrials.gov.
Benefits Persist for Some Patients
The new evidence led the USPSTF to publish new guidelines in 2022, downgrading the recommendation for low-dose aspirin use for primary prevention. Previously, the organization stated that clinicians “should” initiate daily low-dose aspirin in adults aged 50-59 years and “consider” its use in adults aged 60-69 years whose 10-year risk for CVD was higher than 10%.
The updated guidelines stated that the decision to initiate low-dose aspirin in adults aged 40-59 years with a greater than 10% risk for CVD “should be an individual one,” based on professional judgment and individual patient preferences. The USPSTF also recommended against the use of aspirin in anyone over the age of 60.
Meanwhile, the American College of Cardiology and American Heart Association also dialed down previously strong recommendations on low-dose aspirin to a more nuanced recommendation stating, “low-dose aspirin might be considered for primary prevention of ASCVD among select adults 40-70 years of age.”
With a varying age limit for recommending aspirin, clinicians may take into consideration several variables.
“Is there a magic age? I don’t think there is,” said Douglas Lloyd-Jones, the former president of the American Heart Association and current chair of the Department of Preventive Medicine and a practicing cardiologist at Northwestern University Feinberg School of Medicine in Chicago, Illinois.
For a patient over age 60 who is at a high risk for adverse cardiovascular outcomes, is unable to quit smoking, and is not likely to experience problematic bleeding, a clinician might recommend aspirin, Dr. Lloyd-Jones said. He said he sometimes also assesses coronary artery calcium to guide his clinical decisions: If elevated (an Agatston score above 100), he might recommend low-dose aspirin.
Dr. Lloyd-Jones also reiterated that patients should continue taking low-dose aspirin if they have already experienced a heart attack, stroke, episode of atrial fibrillation, or required a vascular stent.
Unless a patient with established CVD has intractable bleeding, “the aspirin is really for life,” Dr. Lloyd-Jones said. Patients who have a stent or who are at high risk for recurrence of stroke are more likely to experience thrombosis, and aspirin can decrease the risk.
“In our cardiology community, we don’t just strictly use the age of 70; the decision is always individualized,” Dr. Maqsood said.
Dr. Wong said primary care providers should focus on the USPSTF’s other recommendations that address CVD (Table), such as smoking cessation and screening for hypertension.
“I think our challenge is that we have so many of those A and B recommendations,” Dr. Wong said. “And I think part of the challenge for us is working with the patient to find out what’s most important to them.”
Discussing heart attacks and strokes often will strike a chord with patients because someone they know has been affected.
Dr. Maqsood emphasized the importance of behavioral interventions, such as helping patients decrease their body mass index and control their hyperlipidemia.
“The behavioral interventions are those which are the most cost-effective without any side effects,” he said.
His other piece of advice is to inquire with younger patients about a family history of heart attacks. Familial hypercholesteremia is unlikely to be controlled by diet and exercise and will need medical therapy.
Dr. Lloyd-Jones described the discussions he has with patients about preventing heart attacks as “the most important conversations we can have: Remember that cardiovascular disease is still the leading cause of death and disability in the world and in the United States.”
Dr. Wong, Dr. Lloyd-Jones, and Dr. Maqsood reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
As the pendulum has swung against recommending aspirin for the primary prevention of heart attacks and strokes, clinicians should focus on other ways to help patients avoid cardiovascular events.
A landmark study published in 1988 in The New England Journal of Medicine reported an astonishing 44% drop in the number of heart attacks among US male physicians aged 40-84 years who took aspirin.
Aspirin subsequently became a daily habit for millions of Americans. In 2017, nearly a quarter of Americans over age 40 who did not have cardiovascular disease (CVD) took the drug, and over 20% of those were doing so without a physician’s recommendation.
But in 2018, three studies (ASCEND, ARRIVE, and ASPREE) showed a stunning reversal in the purported benefit, according to John Wong, MD, vice-chair of the US Preventive Services Task Force (USPSTF).
The calculus for taking aspirin appeared to have changed dramatically: The drug decreased the risk for myocardial infarction by only 11% among study subjects, while its potential harms were much more pronounced.
According to Dr. Wong, who is also a professor of medicine and a primary care physician at Tufts University School of Medicine in Boston, Massachusetts, patients taking low-dose aspirin had a 58% increase in their risk for gastrointestinal bleeding compared with those not on aspirin, as well as a 31% increased risk for intracranial bleeding.
who haven’t had a heart attack or stroke.”
Fewer Americans smoke cigarettes, more realize the benefits of a healthy diet and physical activity, and the medical community better recognizes and treats hypertension. New classes of medications such as statins for high cholesterol are also moving the needle.
But a newer class of drugs may provide a safer replacement for aspirin, according to Muhammad Maqsood, MD, a cardiology fellow at DeBakey Heart and Vascular Center at Methodist Hospital in Houston, Texas. P2Y purinoceptor 12 (P2Y12) inhibitors are effective in lowering the risk for heart attack and stroke in patients with acute coronary syndrome or those undergoing elective percutaneous coronary interventions.
“They have shown a better bleeding profile, especially clopidogrel compared to aspirin,” Dr. Maqsood said.
However, the findings come from trials of patients who already had CVD, so results cannot yet be extrapolated to primary prevention. Dr. Maqsood said the gap highlights the need for clinical trials that evaluate P2Y12 inhibitors for primary prevention, but no such study is registered on clinicaltrials.gov.
Benefits Persist for Some Patients
The new evidence led the USPSTF to publish new guidelines in 2022, downgrading the recommendation for low-dose aspirin use for primary prevention. Previously, the organization stated that clinicians “should” initiate daily low-dose aspirin in adults aged 50-59 years and “consider” its use in adults aged 60-69 years whose 10-year risk for CVD was higher than 10%.
The updated guidelines stated that the decision to initiate low-dose aspirin in adults aged 40-59 years with a greater than 10% risk for CVD “should be an individual one,” based on professional judgment and individual patient preferences. The USPSTF also recommended against the use of aspirin in anyone over the age of 60.
Meanwhile, the American College of Cardiology and American Heart Association also dialed down previously strong recommendations on low-dose aspirin to a more nuanced recommendation stating, “low-dose aspirin might be considered for primary prevention of ASCVD among select adults 40-70 years of age.”
With a varying age limit for recommending aspirin, clinicians may take into consideration several variables.
“Is there a magic age? I don’t think there is,” said Douglas Lloyd-Jones, the former president of the American Heart Association and current chair of the Department of Preventive Medicine and a practicing cardiologist at Northwestern University Feinberg School of Medicine in Chicago, Illinois.
For a patient over age 60 who is at a high risk for adverse cardiovascular outcomes, is unable to quit smoking, and is not likely to experience problematic bleeding, a clinician might recommend aspirin, Dr. Lloyd-Jones said. He said he sometimes also assesses coronary artery calcium to guide his clinical decisions: If elevated (an Agatston score above 100), he might recommend low-dose aspirin.
Dr. Lloyd-Jones also reiterated that patients should continue taking low-dose aspirin if they have already experienced a heart attack, stroke, episode of atrial fibrillation, or required a vascular stent.
Unless a patient with established CVD has intractable bleeding, “the aspirin is really for life,” Dr. Lloyd-Jones said. Patients who have a stent or who are at high risk for recurrence of stroke are more likely to experience thrombosis, and aspirin can decrease the risk.
“In our cardiology community, we don’t just strictly use the age of 70; the decision is always individualized,” Dr. Maqsood said.
Dr. Wong said primary care providers should focus on the USPSTF’s other recommendations that address CVD (Table), such as smoking cessation and screening for hypertension.
“I think our challenge is that we have so many of those A and B recommendations,” Dr. Wong said. “And I think part of the challenge for us is working with the patient to find out what’s most important to them.”
Discussing heart attacks and strokes often will strike a chord with patients because someone they know has been affected.
Dr. Maqsood emphasized the importance of behavioral interventions, such as helping patients decrease their body mass index and control their hyperlipidemia.
“The behavioral interventions are those which are the most cost-effective without any side effects,” he said.
His other piece of advice is to inquire with younger patients about a family history of heart attacks. Familial hypercholesteremia is unlikely to be controlled by diet and exercise and will need medical therapy.
Dr. Lloyd-Jones described the discussions he has with patients about preventing heart attacks as “the most important conversations we can have: Remember that cardiovascular disease is still the leading cause of death and disability in the world and in the United States.”
Dr. Wong, Dr. Lloyd-Jones, and Dr. Maqsood reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
As the pendulum has swung against recommending aspirin for the primary prevention of heart attacks and strokes, clinicians should focus on other ways to help patients avoid cardiovascular events.
A landmark study published in 1988 in The New England Journal of Medicine reported an astonishing 44% drop in the number of heart attacks among US male physicians aged 40-84 years who took aspirin.
Aspirin subsequently became a daily habit for millions of Americans. In 2017, nearly a quarter of Americans over age 40 who did not have cardiovascular disease (CVD) took the drug, and over 20% of those were doing so without a physician’s recommendation.
But in 2018, three studies (ASCEND, ARRIVE, and ASPREE) showed a stunning reversal in the purported benefit, according to John Wong, MD, vice-chair of the US Preventive Services Task Force (USPSTF).
The calculus for taking aspirin appeared to have changed dramatically: The drug decreased the risk for myocardial infarction by only 11% among study subjects, while its potential harms were much more pronounced.
According to Dr. Wong, who is also a professor of medicine and a primary care physician at Tufts University School of Medicine in Boston, Massachusetts, patients taking low-dose aspirin had a 58% increase in their risk for gastrointestinal bleeding compared with those not on aspirin, as well as a 31% increased risk for intracranial bleeding.
who haven’t had a heart attack or stroke.”
Fewer Americans smoke cigarettes, more realize the benefits of a healthy diet and physical activity, and the medical community better recognizes and treats hypertension. New classes of medications such as statins for high cholesterol are also moving the needle.
But a newer class of drugs may provide a safer replacement for aspirin, according to Muhammad Maqsood, MD, a cardiology fellow at DeBakey Heart and Vascular Center at Methodist Hospital in Houston, Texas. P2Y purinoceptor 12 (P2Y12) inhibitors are effective in lowering the risk for heart attack and stroke in patients with acute coronary syndrome or those undergoing elective percutaneous coronary interventions.
“They have shown a better bleeding profile, especially clopidogrel compared to aspirin,” Dr. Maqsood said.
However, the findings come from trials of patients who already had CVD, so results cannot yet be extrapolated to primary prevention. Dr. Maqsood said the gap highlights the need for clinical trials that evaluate P2Y12 inhibitors for primary prevention, but no such study is registered on clinicaltrials.gov.
Benefits Persist for Some Patients
The new evidence led the USPSTF to publish new guidelines in 2022, downgrading the recommendation for low-dose aspirin use for primary prevention. Previously, the organization stated that clinicians “should” initiate daily low-dose aspirin in adults aged 50-59 years and “consider” its use in adults aged 60-69 years whose 10-year risk for CVD was higher than 10%.
The updated guidelines stated that the decision to initiate low-dose aspirin in adults aged 40-59 years with a greater than 10% risk for CVD “should be an individual one,” based on professional judgment and individual patient preferences. The USPSTF also recommended against the use of aspirin in anyone over the age of 60.
Meanwhile, the American College of Cardiology and American Heart Association also dialed down previously strong recommendations on low-dose aspirin to a more nuanced recommendation stating, “low-dose aspirin might be considered for primary prevention of ASCVD among select adults 40-70 years of age.”
With a varying age limit for recommending aspirin, clinicians may take into consideration several variables.
“Is there a magic age? I don’t think there is,” said Douglas Lloyd-Jones, the former president of the American Heart Association and current chair of the Department of Preventive Medicine and a practicing cardiologist at Northwestern University Feinberg School of Medicine in Chicago, Illinois.
For a patient over age 60 who is at a high risk for adverse cardiovascular outcomes, is unable to quit smoking, and is not likely to experience problematic bleeding, a clinician might recommend aspirin, Dr. Lloyd-Jones said. He said he sometimes also assesses coronary artery calcium to guide his clinical decisions: If elevated (an Agatston score above 100), he might recommend low-dose aspirin.
Dr. Lloyd-Jones also reiterated that patients should continue taking low-dose aspirin if they have already experienced a heart attack, stroke, episode of atrial fibrillation, or required a vascular stent.
Unless a patient with established CVD has intractable bleeding, “the aspirin is really for life,” Dr. Lloyd-Jones said. Patients who have a stent or who are at high risk for recurrence of stroke are more likely to experience thrombosis, and aspirin can decrease the risk.
“In our cardiology community, we don’t just strictly use the age of 70; the decision is always individualized,” Dr. Maqsood said.
Dr. Wong said primary care providers should focus on the USPSTF’s other recommendations that address CVD (Table), such as smoking cessation and screening for hypertension.
“I think our challenge is that we have so many of those A and B recommendations,” Dr. Wong said. “And I think part of the challenge for us is working with the patient to find out what’s most important to them.”
Discussing heart attacks and strokes often will strike a chord with patients because someone they know has been affected.
Dr. Maqsood emphasized the importance of behavioral interventions, such as helping patients decrease their body mass index and control their hyperlipidemia.
“The behavioral interventions are those which are the most cost-effective without any side effects,” he said.
His other piece of advice is to inquire with younger patients about a family history of heart attacks. Familial hypercholesteremia is unlikely to be controlled by diet and exercise and will need medical therapy.
Dr. Lloyd-Jones described the discussions he has with patients about preventing heart attacks as “the most important conversations we can have: Remember that cardiovascular disease is still the leading cause of death and disability in the world and in the United States.”
Dr. Wong, Dr. Lloyd-Jones, and Dr. Maqsood reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Vaccine Safety and DMT for Highly Active Multiple Sclerosis: New Data
, new research shows.
The study, the first to examine vaccine safety and immunogenicity in highly active MS, revealed high seroprotection rates following receipt of vaccines for COVID-19 and hepatitis A and B, regardless of the duration of treatment with natalizumab.
On the basis of these findings, investigators created an algorithm that clinicians can use to map an immunization schedule in patients who might otherwise delay initiation of disease-modifying therapy until they are fully vaccinated.
“We observed seroprotection rates exceeding 90% for hepatitis A and B, and mRNA COVID-19 vaccines, and all vaccines demonstrated a favorable safety profile, with no exacerbation of disease activity detected,” said lead author René Carvajal, MD, of the Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. “This points to potential benefits for patients with highly active MS who require both immunization and high-efficacy therapies that may impact vaccine responses.”
The study was published online in JAMA Network Open.
A Controversial Issue
Today’s high-efficacy therapies for MS may increase the risk of acquiring new infections, reactivate latent pathogens, or worsen ongoing infectious conditions, and immunogenicity of vaccination can be compromised by immunosuppressive agents, particularly CD20 therapies, researchers noted.
As a result, many clinicians opt to delay initiation of such therapies until vaccination schedules are complete to avoid exposure to vaccine-preventable infections. But delaying treatment can potentially affect disease progression.
Reports of disease worsening following vaccination “have raised controversy around vaccine safety,” the authors wrote. The issue is especially relevant to those with highly active MS due to the scarcity of available data in this population.
The motivation for the study “stemmed from the complex balance clinicians face between initiating highly effective therapies promptly in patients with highly active MS and ensuring adequate protection against preventable infections through vaccination,” Dr. Carvajal said.
High Seroprotection Rate
Researchers analyzed data on 60 patients (mean age, 43 years; 44 female; mean disease duration, 17 years) participating in one of two prospectively followed cohorts: The Barcelona Clinically Isolated Syndromes Inception Cohort and the Barcelona Treatment Cohort. Data included demographic, clinical, radiologic, and biological data as well as regular clinical assessments, evaluations of the Expanded Disability Status Scale (EDSS), and MRI scans.
Patients enrolled in the current study had received at least one of these vaccines between September 2016 and February 2022: hepatitis A virus (HAV), hepatitis B virus (HBV; enhanced immunity high load or adjuvanted), or COVID-19 (BNT162b2 [Pfizer-BioNTech], mRAN-1273 [Moderna], or ChAdOx1-S [recombinant; AstraZeneca]).
The researchers conducted a retrospective, self-controlled analysis to compare the annualized relapse rate, EDSS score, and new T2 lesions counts during the 12 months before and after vaccination in patients with short- and long-term treatment duration.
They also compared John Cunningham virus serostatus between the two periods, as well as immunoglobulin G titers for each vaccine.
The global seroprotection rate was 93% (95% CI, 86%-98%). Individual vaccine rates were 92% for HAV, 93% for HBV, and 100% for COVID-19.
There was a significant reduction between the pre- and postvaccination periods in mean relapse rates (P = .004) and median number of new T2 lesions (P = .01).
There were no changes in EDSS scores before and after vaccinations and duration of natalizumab treatment had no impact on safety and immunogenicity.
‘Viable Option’
The researchers used their findings to create a proposed algorithm to inform immunization decisions in patients with highly active MS who require prompt initiation of high-efficacy disease-modifying therapy.
The algorithm is “integrated into a risk-minimization strategy tailored for patients with highly active MS, emphasizing in this case the pivotal role of natalizumab in averting treatment delays and providing adequate protection against potentially severe infections,” Dr. Carvajal said.
Participants who initiated or continued treatment with natalizumab completed their vaccination regimen without any incidents of progressive multifocal leukoencephalopathy (PML) or disease activity rebound following natalizumab discontinuation.
This suggests that using natalizumab for a brief duration might be a “viable option to contemplate,” the authors noted.
Commenting on the findings, Grace Gombolay, MD, assistant professor of pediatrics in the Division of Pediatric Neurology and director of the Pediatric Neuroimmunology and Multiple Sclerosis Clinic, Emory University, Atlanta, Georgia, said the study “demonstrates that vaccines are safe and do not trigger attacks in patients with MS on natalizumab, and that immunity — as measured by antibodies — is preserved in MS patients who receive natalizumab.”
This “contrasts with other treatments, as decreased antibody responses in COVID-19 are noted in certain treatments,” said Dr. Gombolay, who was not part of the study. “If both disease control and immunity against infection are the goals for the patient, then natalizumab is a reasonable option.”
“However, this must be balanced with other considerations,” she added, including the risk for PML and pregnancy.
This study was supported by grants from the European Committee for Treatment and Research in Multiple Sclerosis, Instituto de Salud Carlos III, and the European Union. Dr. Carvajal reported receiving grants from Vall d’Hebron Institut de Recerca and the European Committee for Treatment and Research in Multiple Sclerosis and honoraria from Roche, Novartis, BIIB-Colombia, Merck, and Sanofi outside the submitted work. Dr. Gombolay serves as media editor for Pediatric Neurology and as associate editor of the Annals of the Child Neurology Society. She is also a part-time CDC consultant for acute flaccid myelitis and received an honorarium as a speaker at the Georgia Neurological Society meeting, sponsored by Academic CME and TG Therapeutics.
A version of this article appeared on Medscape.com.
, new research shows.
The study, the first to examine vaccine safety and immunogenicity in highly active MS, revealed high seroprotection rates following receipt of vaccines for COVID-19 and hepatitis A and B, regardless of the duration of treatment with natalizumab.
On the basis of these findings, investigators created an algorithm that clinicians can use to map an immunization schedule in patients who might otherwise delay initiation of disease-modifying therapy until they are fully vaccinated.
“We observed seroprotection rates exceeding 90% for hepatitis A and B, and mRNA COVID-19 vaccines, and all vaccines demonstrated a favorable safety profile, with no exacerbation of disease activity detected,” said lead author René Carvajal, MD, of the Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. “This points to potential benefits for patients with highly active MS who require both immunization and high-efficacy therapies that may impact vaccine responses.”
The study was published online in JAMA Network Open.
A Controversial Issue
Today’s high-efficacy therapies for MS may increase the risk of acquiring new infections, reactivate latent pathogens, or worsen ongoing infectious conditions, and immunogenicity of vaccination can be compromised by immunosuppressive agents, particularly CD20 therapies, researchers noted.
As a result, many clinicians opt to delay initiation of such therapies until vaccination schedules are complete to avoid exposure to vaccine-preventable infections. But delaying treatment can potentially affect disease progression.
Reports of disease worsening following vaccination “have raised controversy around vaccine safety,” the authors wrote. The issue is especially relevant to those with highly active MS due to the scarcity of available data in this population.
The motivation for the study “stemmed from the complex balance clinicians face between initiating highly effective therapies promptly in patients with highly active MS and ensuring adequate protection against preventable infections through vaccination,” Dr. Carvajal said.
High Seroprotection Rate
Researchers analyzed data on 60 patients (mean age, 43 years; 44 female; mean disease duration, 17 years) participating in one of two prospectively followed cohorts: The Barcelona Clinically Isolated Syndromes Inception Cohort and the Barcelona Treatment Cohort. Data included demographic, clinical, radiologic, and biological data as well as regular clinical assessments, evaluations of the Expanded Disability Status Scale (EDSS), and MRI scans.
Patients enrolled in the current study had received at least one of these vaccines between September 2016 and February 2022: hepatitis A virus (HAV), hepatitis B virus (HBV; enhanced immunity high load or adjuvanted), or COVID-19 (BNT162b2 [Pfizer-BioNTech], mRAN-1273 [Moderna], or ChAdOx1-S [recombinant; AstraZeneca]).
The researchers conducted a retrospective, self-controlled analysis to compare the annualized relapse rate, EDSS score, and new T2 lesions counts during the 12 months before and after vaccination in patients with short- and long-term treatment duration.
They also compared John Cunningham virus serostatus between the two periods, as well as immunoglobulin G titers for each vaccine.
The global seroprotection rate was 93% (95% CI, 86%-98%). Individual vaccine rates were 92% for HAV, 93% for HBV, and 100% for COVID-19.
There was a significant reduction between the pre- and postvaccination periods in mean relapse rates (P = .004) and median number of new T2 lesions (P = .01).
There were no changes in EDSS scores before and after vaccinations and duration of natalizumab treatment had no impact on safety and immunogenicity.
‘Viable Option’
The researchers used their findings to create a proposed algorithm to inform immunization decisions in patients with highly active MS who require prompt initiation of high-efficacy disease-modifying therapy.
The algorithm is “integrated into a risk-minimization strategy tailored for patients with highly active MS, emphasizing in this case the pivotal role of natalizumab in averting treatment delays and providing adequate protection against potentially severe infections,” Dr. Carvajal said.
Participants who initiated or continued treatment with natalizumab completed their vaccination regimen without any incidents of progressive multifocal leukoencephalopathy (PML) or disease activity rebound following natalizumab discontinuation.
This suggests that using natalizumab for a brief duration might be a “viable option to contemplate,” the authors noted.
Commenting on the findings, Grace Gombolay, MD, assistant professor of pediatrics in the Division of Pediatric Neurology and director of the Pediatric Neuroimmunology and Multiple Sclerosis Clinic, Emory University, Atlanta, Georgia, said the study “demonstrates that vaccines are safe and do not trigger attacks in patients with MS on natalizumab, and that immunity — as measured by antibodies — is preserved in MS patients who receive natalizumab.”
This “contrasts with other treatments, as decreased antibody responses in COVID-19 are noted in certain treatments,” said Dr. Gombolay, who was not part of the study. “If both disease control and immunity against infection are the goals for the patient, then natalizumab is a reasonable option.”
“However, this must be balanced with other considerations,” she added, including the risk for PML and pregnancy.
This study was supported by grants from the European Committee for Treatment and Research in Multiple Sclerosis, Instituto de Salud Carlos III, and the European Union. Dr. Carvajal reported receiving grants from Vall d’Hebron Institut de Recerca and the European Committee for Treatment and Research in Multiple Sclerosis and honoraria from Roche, Novartis, BIIB-Colombia, Merck, and Sanofi outside the submitted work. Dr. Gombolay serves as media editor for Pediatric Neurology and as associate editor of the Annals of the Child Neurology Society. She is also a part-time CDC consultant for acute flaccid myelitis and received an honorarium as a speaker at the Georgia Neurological Society meeting, sponsored by Academic CME and TG Therapeutics.
A version of this article appeared on Medscape.com.
, new research shows.
The study, the first to examine vaccine safety and immunogenicity in highly active MS, revealed high seroprotection rates following receipt of vaccines for COVID-19 and hepatitis A and B, regardless of the duration of treatment with natalizumab.
On the basis of these findings, investigators created an algorithm that clinicians can use to map an immunization schedule in patients who might otherwise delay initiation of disease-modifying therapy until they are fully vaccinated.
“We observed seroprotection rates exceeding 90% for hepatitis A and B, and mRNA COVID-19 vaccines, and all vaccines demonstrated a favorable safety profile, with no exacerbation of disease activity detected,” said lead author René Carvajal, MD, of the Department of Neurology-Neuroimmunology, Multiple Sclerosis Centre of Catalonia (Cemcat), Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. “This points to potential benefits for patients with highly active MS who require both immunization and high-efficacy therapies that may impact vaccine responses.”
The study was published online in JAMA Network Open.
A Controversial Issue
Today’s high-efficacy therapies for MS may increase the risk of acquiring new infections, reactivate latent pathogens, or worsen ongoing infectious conditions, and immunogenicity of vaccination can be compromised by immunosuppressive agents, particularly CD20 therapies, researchers noted.
As a result, many clinicians opt to delay initiation of such therapies until vaccination schedules are complete to avoid exposure to vaccine-preventable infections. But delaying treatment can potentially affect disease progression.
Reports of disease worsening following vaccination “have raised controversy around vaccine safety,” the authors wrote. The issue is especially relevant to those with highly active MS due to the scarcity of available data in this population.
The motivation for the study “stemmed from the complex balance clinicians face between initiating highly effective therapies promptly in patients with highly active MS and ensuring adequate protection against preventable infections through vaccination,” Dr. Carvajal said.
High Seroprotection Rate
Researchers analyzed data on 60 patients (mean age, 43 years; 44 female; mean disease duration, 17 years) participating in one of two prospectively followed cohorts: The Barcelona Clinically Isolated Syndromes Inception Cohort and the Barcelona Treatment Cohort. Data included demographic, clinical, radiologic, and biological data as well as regular clinical assessments, evaluations of the Expanded Disability Status Scale (EDSS), and MRI scans.
Patients enrolled in the current study had received at least one of these vaccines between September 2016 and February 2022: hepatitis A virus (HAV), hepatitis B virus (HBV; enhanced immunity high load or adjuvanted), or COVID-19 (BNT162b2 [Pfizer-BioNTech], mRAN-1273 [Moderna], or ChAdOx1-S [recombinant; AstraZeneca]).
The researchers conducted a retrospective, self-controlled analysis to compare the annualized relapse rate, EDSS score, and new T2 lesions counts during the 12 months before and after vaccination in patients with short- and long-term treatment duration.
They also compared John Cunningham virus serostatus between the two periods, as well as immunoglobulin G titers for each vaccine.
The global seroprotection rate was 93% (95% CI, 86%-98%). Individual vaccine rates were 92% for HAV, 93% for HBV, and 100% for COVID-19.
There was a significant reduction between the pre- and postvaccination periods in mean relapse rates (P = .004) and median number of new T2 lesions (P = .01).
There were no changes in EDSS scores before and after vaccinations and duration of natalizumab treatment had no impact on safety and immunogenicity.
‘Viable Option’
The researchers used their findings to create a proposed algorithm to inform immunization decisions in patients with highly active MS who require prompt initiation of high-efficacy disease-modifying therapy.
The algorithm is “integrated into a risk-minimization strategy tailored for patients with highly active MS, emphasizing in this case the pivotal role of natalizumab in averting treatment delays and providing adequate protection against potentially severe infections,” Dr. Carvajal said.
Participants who initiated or continued treatment with natalizumab completed their vaccination regimen without any incidents of progressive multifocal leukoencephalopathy (PML) or disease activity rebound following natalizumab discontinuation.
This suggests that using natalizumab for a brief duration might be a “viable option to contemplate,” the authors noted.
Commenting on the findings, Grace Gombolay, MD, assistant professor of pediatrics in the Division of Pediatric Neurology and director of the Pediatric Neuroimmunology and Multiple Sclerosis Clinic, Emory University, Atlanta, Georgia, said the study “demonstrates that vaccines are safe and do not trigger attacks in patients with MS on natalizumab, and that immunity — as measured by antibodies — is preserved in MS patients who receive natalizumab.”
This “contrasts with other treatments, as decreased antibody responses in COVID-19 are noted in certain treatments,” said Dr. Gombolay, who was not part of the study. “If both disease control and immunity against infection are the goals for the patient, then natalizumab is a reasonable option.”
“However, this must be balanced with other considerations,” she added, including the risk for PML and pregnancy.
This study was supported by grants from the European Committee for Treatment and Research in Multiple Sclerosis, Instituto de Salud Carlos III, and the European Union. Dr. Carvajal reported receiving grants from Vall d’Hebron Institut de Recerca and the European Committee for Treatment and Research in Multiple Sclerosis and honoraria from Roche, Novartis, BIIB-Colombia, Merck, and Sanofi outside the submitted work. Dr. Gombolay serves as media editor for Pediatric Neurology and as associate editor of the Annals of the Child Neurology Society. She is also a part-time CDC consultant for acute flaccid myelitis and received an honorarium as a speaker at the Georgia Neurological Society meeting, sponsored by Academic CME and TG Therapeutics.
A version of this article appeared on Medscape.com.
FROM JAMA OPEN NETWORK
Device Uses Sleep Data to Pinpoint Stress Risk
TOPLINE:
Decreased total sleep time (TST) and increased resting heart rate (RHR), heart rate variability (HRV), and average nightly respiratory rate (ARR) as measured by a multisensor device worn during sleep accurately correlated with self-reported stress levels in college students, a new study suggests.
METHODOLOGY:
- First-semester college students (n = 525; aged 18-24 years) enrolled in the Lived Experiences measured Using Rings Study (LEMURS) provided continuous biometric data via a wearable device (Oura Ring; Oura Health) and answered weekly surveys regarding stress levels.
- The researchers used mixed-effects regression models to identify associations between perceived stress scores and average nightly TST, RHR, HRV, and ARR.
TAKEAWAY:
- Consistent associations were found between perceived stress scores and TST, RHR, HRV, and ARR, which persisted even after controlling for gender and week of the semester.
- Risk for moderate to high stress decreased by 38% with every additional hour of TST (P < .01) and by 1.2% with each millisecond increase in HRV (P < .05).
- Moderate to high stress risk increased by 3.6% with each beat-per-minute-increase in RHR (P < .01) and by 23% with each additional breath-per-minute increase in ARR (P < .01).
- Participants who identified as female, nonbinary, or transgender reported significantly higher stress throughout the study.
IN PRACTICE:
“The present work highlights the potential utility of monitoring sleep, suggesting that these measures may identify within individual changes that are concerning for stress. As the demand for mental health services grows, determining which wearable-derived sleep estimates provide information about well-being and can predict worsening mental health in young adults is an important area of study,” study authors wrote.
SOURCE:
The study, led by Laura S.P. Bloomfield, University of Vermont, Burlington, Vermont, was published online in PLOS Digital Health.
LIMITATIONS:
The study focused on raw sleep measures; the researchers suggest that future studies evaluate additional sleep variables (eg, daytime naps), which have been associated with mental health in college students. In addition, the researchers did not have stress or sleep data before participants started college, so they could not assess the impact of starting college on participants’ sleep.
DISCLOSURES:
Bloomfield was supported by the Gund Fellowship and received a partial salary from the Mass Mutual Insurance Wellness Initiative. Other authors’ funding is reported in the original article.
A version of this article appeared on Medscape.com.
TOPLINE:
Decreased total sleep time (TST) and increased resting heart rate (RHR), heart rate variability (HRV), and average nightly respiratory rate (ARR) as measured by a multisensor device worn during sleep accurately correlated with self-reported stress levels in college students, a new study suggests.
METHODOLOGY:
- First-semester college students (n = 525; aged 18-24 years) enrolled in the Lived Experiences measured Using Rings Study (LEMURS) provided continuous biometric data via a wearable device (Oura Ring; Oura Health) and answered weekly surveys regarding stress levels.
- The researchers used mixed-effects regression models to identify associations between perceived stress scores and average nightly TST, RHR, HRV, and ARR.
TAKEAWAY:
- Consistent associations were found between perceived stress scores and TST, RHR, HRV, and ARR, which persisted even after controlling for gender and week of the semester.
- Risk for moderate to high stress decreased by 38% with every additional hour of TST (P < .01) and by 1.2% with each millisecond increase in HRV (P < .05).
- Moderate to high stress risk increased by 3.6% with each beat-per-minute-increase in RHR (P < .01) and by 23% with each additional breath-per-minute increase in ARR (P < .01).
- Participants who identified as female, nonbinary, or transgender reported significantly higher stress throughout the study.
IN PRACTICE:
“The present work highlights the potential utility of monitoring sleep, suggesting that these measures may identify within individual changes that are concerning for stress. As the demand for mental health services grows, determining which wearable-derived sleep estimates provide information about well-being and can predict worsening mental health in young adults is an important area of study,” study authors wrote.
SOURCE:
The study, led by Laura S.P. Bloomfield, University of Vermont, Burlington, Vermont, was published online in PLOS Digital Health.
LIMITATIONS:
The study focused on raw sleep measures; the researchers suggest that future studies evaluate additional sleep variables (eg, daytime naps), which have been associated with mental health in college students. In addition, the researchers did not have stress or sleep data before participants started college, so they could not assess the impact of starting college on participants’ sleep.
DISCLOSURES:
Bloomfield was supported by the Gund Fellowship and received a partial salary from the Mass Mutual Insurance Wellness Initiative. Other authors’ funding is reported in the original article.
A version of this article appeared on Medscape.com.
TOPLINE:
Decreased total sleep time (TST) and increased resting heart rate (RHR), heart rate variability (HRV), and average nightly respiratory rate (ARR) as measured by a multisensor device worn during sleep accurately correlated with self-reported stress levels in college students, a new study suggests.
METHODOLOGY:
- First-semester college students (n = 525; aged 18-24 years) enrolled in the Lived Experiences measured Using Rings Study (LEMURS) provided continuous biometric data via a wearable device (Oura Ring; Oura Health) and answered weekly surveys regarding stress levels.
- The researchers used mixed-effects regression models to identify associations between perceived stress scores and average nightly TST, RHR, HRV, and ARR.
TAKEAWAY:
- Consistent associations were found between perceived stress scores and TST, RHR, HRV, and ARR, which persisted even after controlling for gender and week of the semester.
- Risk for moderate to high stress decreased by 38% with every additional hour of TST (P < .01) and by 1.2% with each millisecond increase in HRV (P < .05).
- Moderate to high stress risk increased by 3.6% with each beat-per-minute-increase in RHR (P < .01) and by 23% with each additional breath-per-minute increase in ARR (P < .01).
- Participants who identified as female, nonbinary, or transgender reported significantly higher stress throughout the study.
IN PRACTICE:
“The present work highlights the potential utility of monitoring sleep, suggesting that these measures may identify within individual changes that are concerning for stress. As the demand for mental health services grows, determining which wearable-derived sleep estimates provide information about well-being and can predict worsening mental health in young adults is an important area of study,” study authors wrote.
SOURCE:
The study, led by Laura S.P. Bloomfield, University of Vermont, Burlington, Vermont, was published online in PLOS Digital Health.
LIMITATIONS:
The study focused on raw sleep measures; the researchers suggest that future studies evaluate additional sleep variables (eg, daytime naps), which have been associated with mental health in college students. In addition, the researchers did not have stress or sleep data before participants started college, so they could not assess the impact of starting college on participants’ sleep.
DISCLOSURES:
Bloomfield was supported by the Gund Fellowship and received a partial salary from the Mass Mutual Insurance Wellness Initiative. Other authors’ funding is reported in the original article.
A version of this article appeared on Medscape.com.
Evening May Be the Best Time for Exercise
TOPLINE:
Moderate to vigorous aerobic physical activity performed in the evening is associated with the lowest risk for mortality, cardiovascular disease (CVD), and microvascular disease (MVD) in adults with obesity, including those with type 2 diabetes (T2D).
METHODOLOGY:
- Bouts of moderate to vigorous aerobic physical activity are widely recognized to improve cardiometabolic risk factors, but whether morning, afternoon, or evening timing may lead to greater improvements is unclear.
- Researchers analyzed UK Biobank data of 29,836 participants with obesity (body mass index, › 30; mean age, 62.2 years; 53.2% women), including 2995 also diagnosed with T2D, all enrolled in 2006-2010.
- Aerobic activity was defined as bouts lasting ≥ 3 minutes, and the intensity of activity was classified as light, moderate, or vigorous using accelerometer data collected from participants.
- Participants were stratified into the morning (6 a.m. to < 12 p.m.), afternoon (12 p.m. to < 6 p.m.), and evening (6 p.m. to < 12 a.m.) groups based on when > 50% of their total moderate to vigorous activity occurred, and those with no aerobic bouts were considered the reference group.
- The association between the timing of aerobic physical activity and risk for all-cause mortality, CVD (defined as circulatory, such as hypertension), and MVD (neuropathy, nephropathy, or retinopathy) was evaluated over a median follow-up of 7.9 years.
TAKEAWAY:
- Mortality risk was lower in the afternoon (HR, 0.60; 95% CI, 0.51-0.71) and morning (HR, 0.67; 95% CI, 0.56-0.79) activity groups than in the reference group, but this association was weaker than that observed in the evening activity group.
- The evening moderate to vigorous activity group had a lower risk for CVD (HR, 0.64; 95% CI, 0.54-0.75) and MVD (HR, 0.76; 95% CI, 0.63-0.92) than the reference group.
- Among participants with obesity and T2D, moderate to vigorous physical activity in the evening was associated with a lower risk for mortality, CVD, and MVD.
IN PRACTICE:
The authors wrote, “The results of this study emphasize that beyond the total volume of MVPA [moderate to vigorous physical activity], its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows.”
SOURCE:
The study, led by Angelo Sabag, PhD, Charles Perkins Centre, University of Sydney, Australia, was published online in Diabetes Care.
LIMITATIONS:
Because this was an observational study, the possibility of reverse causation from prodromal disease and unaccounted confounding factors could not have been ruled out. There was a lag of a median of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study. Moreover, the response rate of the UK Biobank was low.
DISCLOSURES:
The study was funded by an Australian National Health and Medical Research Council Investigator Grant and the National Heart Foundation of Australia Postdoctoral Fellowship. The authors reported no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Moderate to vigorous aerobic physical activity performed in the evening is associated with the lowest risk for mortality, cardiovascular disease (CVD), and microvascular disease (MVD) in adults with obesity, including those with type 2 diabetes (T2D).
METHODOLOGY:
- Bouts of moderate to vigorous aerobic physical activity are widely recognized to improve cardiometabolic risk factors, but whether morning, afternoon, or evening timing may lead to greater improvements is unclear.
- Researchers analyzed UK Biobank data of 29,836 participants with obesity (body mass index, › 30; mean age, 62.2 years; 53.2% women), including 2995 also diagnosed with T2D, all enrolled in 2006-2010.
- Aerobic activity was defined as bouts lasting ≥ 3 minutes, and the intensity of activity was classified as light, moderate, or vigorous using accelerometer data collected from participants.
- Participants were stratified into the morning (6 a.m. to < 12 p.m.), afternoon (12 p.m. to < 6 p.m.), and evening (6 p.m. to < 12 a.m.) groups based on when > 50% of their total moderate to vigorous activity occurred, and those with no aerobic bouts were considered the reference group.
- The association between the timing of aerobic physical activity and risk for all-cause mortality, CVD (defined as circulatory, such as hypertension), and MVD (neuropathy, nephropathy, or retinopathy) was evaluated over a median follow-up of 7.9 years.
TAKEAWAY:
- Mortality risk was lower in the afternoon (HR, 0.60; 95% CI, 0.51-0.71) and morning (HR, 0.67; 95% CI, 0.56-0.79) activity groups than in the reference group, but this association was weaker than that observed in the evening activity group.
- The evening moderate to vigorous activity group had a lower risk for CVD (HR, 0.64; 95% CI, 0.54-0.75) and MVD (HR, 0.76; 95% CI, 0.63-0.92) than the reference group.
- Among participants with obesity and T2D, moderate to vigorous physical activity in the evening was associated with a lower risk for mortality, CVD, and MVD.
IN PRACTICE:
The authors wrote, “The results of this study emphasize that beyond the total volume of MVPA [moderate to vigorous physical activity], its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows.”
SOURCE:
The study, led by Angelo Sabag, PhD, Charles Perkins Centre, University of Sydney, Australia, was published online in Diabetes Care.
LIMITATIONS:
Because this was an observational study, the possibility of reverse causation from prodromal disease and unaccounted confounding factors could not have been ruled out. There was a lag of a median of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study. Moreover, the response rate of the UK Biobank was low.
DISCLOSURES:
The study was funded by an Australian National Health and Medical Research Council Investigator Grant and the National Heart Foundation of Australia Postdoctoral Fellowship. The authors reported no conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Moderate to vigorous aerobic physical activity performed in the evening is associated with the lowest risk for mortality, cardiovascular disease (CVD), and microvascular disease (MVD) in adults with obesity, including those with type 2 diabetes (T2D).
METHODOLOGY:
- Bouts of moderate to vigorous aerobic physical activity are widely recognized to improve cardiometabolic risk factors, but whether morning, afternoon, or evening timing may lead to greater improvements is unclear.
- Researchers analyzed UK Biobank data of 29,836 participants with obesity (body mass index, › 30; mean age, 62.2 years; 53.2% women), including 2995 also diagnosed with T2D, all enrolled in 2006-2010.
- Aerobic activity was defined as bouts lasting ≥ 3 minutes, and the intensity of activity was classified as light, moderate, or vigorous using accelerometer data collected from participants.
- Participants were stratified into the morning (6 a.m. to < 12 p.m.), afternoon (12 p.m. to < 6 p.m.), and evening (6 p.m. to < 12 a.m.) groups based on when > 50% of their total moderate to vigorous activity occurred, and those with no aerobic bouts were considered the reference group.
- The association between the timing of aerobic physical activity and risk for all-cause mortality, CVD (defined as circulatory, such as hypertension), and MVD (neuropathy, nephropathy, or retinopathy) was evaluated over a median follow-up of 7.9 years.
TAKEAWAY:
- Mortality risk was lower in the afternoon (HR, 0.60; 95% CI, 0.51-0.71) and morning (HR, 0.67; 95% CI, 0.56-0.79) activity groups than in the reference group, but this association was weaker than that observed in the evening activity group.
- The evening moderate to vigorous activity group had a lower risk for CVD (HR, 0.64; 95% CI, 0.54-0.75) and MVD (HR, 0.76; 95% CI, 0.63-0.92) than the reference group.
- Among participants with obesity and T2D, moderate to vigorous physical activity in the evening was associated with a lower risk for mortality, CVD, and MVD.
IN PRACTICE:
The authors wrote, “The results of this study emphasize that beyond the total volume of MVPA [moderate to vigorous physical activity], its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows.”
SOURCE:
The study, led by Angelo Sabag, PhD, Charles Perkins Centre, University of Sydney, Australia, was published online in Diabetes Care.
LIMITATIONS:
Because this was an observational study, the possibility of reverse causation from prodromal disease and unaccounted confounding factors could not have been ruled out. There was a lag of a median of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study. Moreover, the response rate of the UK Biobank was low.
DISCLOSURES:
The study was funded by an Australian National Health and Medical Research Council Investigator Grant and the National Heart Foundation of Australia Postdoctoral Fellowship. The authors reported no conflicts of interest.
A version of this article appeared on Medscape.com.
Automated Risk Assessment Tool Reduces Antibiotic Prescribing Rates
An algorithm-driven risk assessment embedded in an electronic health record (EHR) helped clinicians reduce inappropriate broad-spectrum antibiotic prescribing by 17.4% and 28.4% in patients with UTIs and pneumonia, respectively, according to two related studies published in JAMA.
The randomized control trials included more than 200,000 adult patients with non–life threatening pneumonia or urinary tract infections (UTIs) in 59 hospitals owned by HCA Healthcare across the country.
Researchers analyzed baseline prescribing behaviors over an 18-month period starting in April 2017, and data from a 15-month period of implementation of the new antibiotic system starting in April 2019.
, according to lead author Shruti K. Gohil, MD, MPH, associate medical director of epidemiology and infection prevention, infectious diseases at the University of California Irvine School of Medicine.
“When a patient comes in with pneumonia or a UTI, it’s precisely because we are concerned that our patients have a multidrug-resistant organism that we end up using broad-spectrum antibiotics,” she said.
Despite growing awareness of the need to reduce unnecessary antibiotic use, clinicians have still been slow to adopt a more conservative approach to prescribing, Dr. Gohil said.
“What physicians have been needing is something to hang their hat on, to be able to say, ‘Okay, well, this one’s a low-risk person,’ ” Dr. Gohil said.
The trials compared the impact of routine antibiotic activities with a stewardship bundle, called INSPIRE (Intelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection).
Both groups received educational materials, quarterly coaching calls, prospective evaluations for antibiotic use, and were required to select a reason for prescribing an antibiotic.
But prescribers in the intervention group took part in monthly coaching calls and feedback reports. In addition, if a clinician ordered a broad-spectrum antibiotic to treat pneumonia or a UTI outside of the intensive care unit within 72 hours of admission, an EHR prompt would pop up. The pop-up suggested a standard-spectrum antibiotic instead if patient risk for developing a multidrug-resistant (MDRO) version of either condition was less than 10%.
An algorithm used data from the EHR calculated risk, using factors like patient demographics and history and MDRO infection at the community and hospital level.
Prescribing rates were based on the number of days a patient received a broad-spectrum antibiotic during the first 72 hours of hospitalization.
For the UTI intervention group, rates dropped by 17.4% (rate ratio [RR], 0.83; 95% CI, 0.77-0.89; P < .001), and 28.4% reduction in the pneumonia group (RR, 0.72; 95% CI, 0.66-0.78; P < .001).
“We cannot know which element — prompt, education, or feedback — worked, but the data suggests that the prompt was the main driver,” Dr. Gohil said.
“In antibiotic stewardship, we have learned not only that doctors want to do the right thing, but that we as stewards need to make it easy for them do the right thing,” said Paul Pottinger, MD, professor of medicine at the Division of Allergy and Infectious Diseases at the University of Washington Medical Center in Seattle.
The prompt “is your easy button,” said Dr. Pottinger, who was not involved with either study. “The researchers made it simple, fast, and straightforward, so people don’t have to think about it too much.”
The studies showed similar safety outcomes for the control and intervention groups. Among patients with a UTI, those in the control group were transferred to the ICU after an average of 6.6 days compared to 7 days in the intervention group. Among patients with pneumonia, the average days to ICU transfer were 6.5 for the control group and 7.1 for the intervention group.
“This study is a proof of concept that physicians want to do the right thing and are willing to trust this information,” Dr. Pottinger said. “And this also shows us that this tool can be refined and made even more precise over time.”
The study was funded by the US Centers for Disease Control and Prevention and was led by the University of California Irvine, Harvard Pilgrim Healthcare Institute, and HCA Healthcare System. Various authors report funding and support from entities outside the submitted work. The full list can be found with the original articles.
A version of this article appeared on Medscape.com.
An algorithm-driven risk assessment embedded in an electronic health record (EHR) helped clinicians reduce inappropriate broad-spectrum antibiotic prescribing by 17.4% and 28.4% in patients with UTIs and pneumonia, respectively, according to two related studies published in JAMA.
The randomized control trials included more than 200,000 adult patients with non–life threatening pneumonia or urinary tract infections (UTIs) in 59 hospitals owned by HCA Healthcare across the country.
Researchers analyzed baseline prescribing behaviors over an 18-month period starting in April 2017, and data from a 15-month period of implementation of the new antibiotic system starting in April 2019.
, according to lead author Shruti K. Gohil, MD, MPH, associate medical director of epidemiology and infection prevention, infectious diseases at the University of California Irvine School of Medicine.
“When a patient comes in with pneumonia or a UTI, it’s precisely because we are concerned that our patients have a multidrug-resistant organism that we end up using broad-spectrum antibiotics,” she said.
Despite growing awareness of the need to reduce unnecessary antibiotic use, clinicians have still been slow to adopt a more conservative approach to prescribing, Dr. Gohil said.
“What physicians have been needing is something to hang their hat on, to be able to say, ‘Okay, well, this one’s a low-risk person,’ ” Dr. Gohil said.
The trials compared the impact of routine antibiotic activities with a stewardship bundle, called INSPIRE (Intelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection).
Both groups received educational materials, quarterly coaching calls, prospective evaluations for antibiotic use, and were required to select a reason for prescribing an antibiotic.
But prescribers in the intervention group took part in monthly coaching calls and feedback reports. In addition, if a clinician ordered a broad-spectrum antibiotic to treat pneumonia or a UTI outside of the intensive care unit within 72 hours of admission, an EHR prompt would pop up. The pop-up suggested a standard-spectrum antibiotic instead if patient risk for developing a multidrug-resistant (MDRO) version of either condition was less than 10%.
An algorithm used data from the EHR calculated risk, using factors like patient demographics and history and MDRO infection at the community and hospital level.
Prescribing rates were based on the number of days a patient received a broad-spectrum antibiotic during the first 72 hours of hospitalization.
For the UTI intervention group, rates dropped by 17.4% (rate ratio [RR], 0.83; 95% CI, 0.77-0.89; P < .001), and 28.4% reduction in the pneumonia group (RR, 0.72; 95% CI, 0.66-0.78; P < .001).
“We cannot know which element — prompt, education, or feedback — worked, but the data suggests that the prompt was the main driver,” Dr. Gohil said.
“In antibiotic stewardship, we have learned not only that doctors want to do the right thing, but that we as stewards need to make it easy for them do the right thing,” said Paul Pottinger, MD, professor of medicine at the Division of Allergy and Infectious Diseases at the University of Washington Medical Center in Seattle.
The prompt “is your easy button,” said Dr. Pottinger, who was not involved with either study. “The researchers made it simple, fast, and straightforward, so people don’t have to think about it too much.”
The studies showed similar safety outcomes for the control and intervention groups. Among patients with a UTI, those in the control group were transferred to the ICU after an average of 6.6 days compared to 7 days in the intervention group. Among patients with pneumonia, the average days to ICU transfer were 6.5 for the control group and 7.1 for the intervention group.
“This study is a proof of concept that physicians want to do the right thing and are willing to trust this information,” Dr. Pottinger said. “And this also shows us that this tool can be refined and made even more precise over time.”
The study was funded by the US Centers for Disease Control and Prevention and was led by the University of California Irvine, Harvard Pilgrim Healthcare Institute, and HCA Healthcare System. Various authors report funding and support from entities outside the submitted work. The full list can be found with the original articles.
A version of this article appeared on Medscape.com.
An algorithm-driven risk assessment embedded in an electronic health record (EHR) helped clinicians reduce inappropriate broad-spectrum antibiotic prescribing by 17.4% and 28.4% in patients with UTIs and pneumonia, respectively, according to two related studies published in JAMA.
The randomized control trials included more than 200,000 adult patients with non–life threatening pneumonia or urinary tract infections (UTIs) in 59 hospitals owned by HCA Healthcare across the country.
Researchers analyzed baseline prescribing behaviors over an 18-month period starting in April 2017, and data from a 15-month period of implementation of the new antibiotic system starting in April 2019.
, according to lead author Shruti K. Gohil, MD, MPH, associate medical director of epidemiology and infection prevention, infectious diseases at the University of California Irvine School of Medicine.
“When a patient comes in with pneumonia or a UTI, it’s precisely because we are concerned that our patients have a multidrug-resistant organism that we end up using broad-spectrum antibiotics,” she said.
Despite growing awareness of the need to reduce unnecessary antibiotic use, clinicians have still been slow to adopt a more conservative approach to prescribing, Dr. Gohil said.
“What physicians have been needing is something to hang their hat on, to be able to say, ‘Okay, well, this one’s a low-risk person,’ ” Dr. Gohil said.
The trials compared the impact of routine antibiotic activities with a stewardship bundle, called INSPIRE (Intelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection).
Both groups received educational materials, quarterly coaching calls, prospective evaluations for antibiotic use, and were required to select a reason for prescribing an antibiotic.
But prescribers in the intervention group took part in monthly coaching calls and feedback reports. In addition, if a clinician ordered a broad-spectrum antibiotic to treat pneumonia or a UTI outside of the intensive care unit within 72 hours of admission, an EHR prompt would pop up. The pop-up suggested a standard-spectrum antibiotic instead if patient risk for developing a multidrug-resistant (MDRO) version of either condition was less than 10%.
An algorithm used data from the EHR calculated risk, using factors like patient demographics and history and MDRO infection at the community and hospital level.
Prescribing rates were based on the number of days a patient received a broad-spectrum antibiotic during the first 72 hours of hospitalization.
For the UTI intervention group, rates dropped by 17.4% (rate ratio [RR], 0.83; 95% CI, 0.77-0.89; P < .001), and 28.4% reduction in the pneumonia group (RR, 0.72; 95% CI, 0.66-0.78; P < .001).
“We cannot know which element — prompt, education, or feedback — worked, but the data suggests that the prompt was the main driver,” Dr. Gohil said.
“In antibiotic stewardship, we have learned not only that doctors want to do the right thing, but that we as stewards need to make it easy for them do the right thing,” said Paul Pottinger, MD, professor of medicine at the Division of Allergy and Infectious Diseases at the University of Washington Medical Center in Seattle.
The prompt “is your easy button,” said Dr. Pottinger, who was not involved with either study. “The researchers made it simple, fast, and straightforward, so people don’t have to think about it too much.”
The studies showed similar safety outcomes for the control and intervention groups. Among patients with a UTI, those in the control group were transferred to the ICU after an average of 6.6 days compared to 7 days in the intervention group. Among patients with pneumonia, the average days to ICU transfer were 6.5 for the control group and 7.1 for the intervention group.
“This study is a proof of concept that physicians want to do the right thing and are willing to trust this information,” Dr. Pottinger said. “And this also shows us that this tool can be refined and made even more precise over time.”
The study was funded by the US Centers for Disease Control and Prevention and was led by the University of California Irvine, Harvard Pilgrim Healthcare Institute, and HCA Healthcare System. Various authors report funding and support from entities outside the submitted work. The full list can be found with the original articles.
A version of this article appeared on Medscape.com.
Study Demonstrates Faster Recovery, Less Pain After Facial Resurfacing With 2910-nm Laser
BALTIMORE — A — while causing less discomfort and downtime compared with conventional fractional lasers, a small single-center study showed.
The study enrolled 15 patients who had three treatment sessions with the 2910-nm laser. “It’s highly customizable,” the study’s lead author, Taryn Murray, MD, a dermatologist at Cleveland Clinic, told this news organization. “It has a really fast time in healing compared to traditional abatable lasers; the healing time is 5-7 days vs several weeks.” Dr. Murray presented the results at the annual meeting of the American Society for Laser Medicine and Surgery (ASLMS).
The Technology Behind the Laser
The 2910-nm erbium-doped fluoride glass fiber laser is a mid-infrared ablative fractional device that operates at peak water absorption. It’s designed to cause minimal residual thermal damage, resulting in less discomfort, shorter downtime, and potentially fewer side effects than conventional ablative lasers, Dr. Murray said.
Because of the way the pulses are delivered, “it’s far less painful than traditional fractional ablative lasers, so you can use mainly topical numbing; you don’t need nerve blocks, you don’t have to infiltrate lidocaine, you don’t have to put the patient under anesthesia,” she said.
“Because of the wavelength, how pulses are delivered and how customizable the settings are, it’s safer to use in darker skin types,” and the density, depth, and the amount of coagulation applied into the skin are customizable, Dr. Murray added.
The laser also delivers pulses in a different way than the conventional 2940-nm erbium and CO2 lasers, she explained. “Traditional lasers do it all in one pulse. This laser uses micropulses with relaxation time in between pulses, so the body interprets it as less painful and allows pressure and steam to escape out of the channel, which results in faster healing.”
The study patients had topical anesthetic cream applied to their faces 45-60 minutes before the procedure. Multiple passes were made using both superficial and deep laser modes. The average patient age was 65.7 years, and Fitzpatrick skin types included I (n = 3), II (n = 3), III (n = 7), and IV (n = 2). On a scale of 0-10, the average level of discomfort was 4.9, and the average patient satisfaction after three treatments was 4.8, Dr. Murray said.
For cosmetic improvement, the study used the 5-point Global Aesthetic Improvement Scale (GAIS). Blinded reviewers evaluated digital images and determined an average GAIS score of 3.2 for overall appearance, 2.9 for wrinkles, 3.6 for pigment, 3.1 for skin texture, and 2.6 for skin laxity.
When the patients themselves reviewed the digital images, the average GAIS score was 3.8 for overall appearance.
Side effects, said Dr. Murray, were transient, with edema and soft-tissue crusting lasting 3-5 days and erythema resolving in 1-2 weeks on average. One case of postinflammatory hyperpigmentation (PIH) did arise, which was linked to allergic contact dermatitis from the healing ointment. That patient stayed in the study and had complete resolution of the PIH.
Study Stands Out
A number of studies of the 2910-nm erbium-doped fluoride glass fiber laser have emerged over the past half year, Ritu Swali, MD, who was an American Society of Dermatologic Surgery fellow at a practice in Houston, said in an interview at the meeting. But this one stands out because of the evidence surrounding its use.
Most people are using this laser for facial resurfacing, “and we want to know that we have a technology ... with shorter downtime and easier wound care and just more comfort,” she said.
She noted that with conventional lasers, most patients get nerve blocks and some even opt for general anesthesia. “To be able to do the levels of facial resurfacing [Dr. Murray] is doing without having to do all of that pain management is pretty amazing,” Dr. Swali added.
The speed of the procedure and the relatively short downtime are also noteworthy, she said. “The huge advantage is having so much less pain from the procedure itself, so you’re able to do it faster because they’re tolerating it so well and you’re not having to take breaks,” she said.
As for downtime, Dr. Swali added, “these patients are coming in on a Thursday and they are back up and running by Monday,” as opposed to weeks that is typical with a conventional laser. This laser platform also avoids the pigmentation problems that can come with continuing and aggressive treatment with conventional lasers, she said.
Dr. Murray disclosed relationships with Acclaro Medical, the manufacturer of the laser. Dr. Swali has no relationships to disclose.
A version of this article first appeared on Medscape.com.
BALTIMORE — A — while causing less discomfort and downtime compared with conventional fractional lasers, a small single-center study showed.
The study enrolled 15 patients who had three treatment sessions with the 2910-nm laser. “It’s highly customizable,” the study’s lead author, Taryn Murray, MD, a dermatologist at Cleveland Clinic, told this news organization. “It has a really fast time in healing compared to traditional abatable lasers; the healing time is 5-7 days vs several weeks.” Dr. Murray presented the results at the annual meeting of the American Society for Laser Medicine and Surgery (ASLMS).
The Technology Behind the Laser
The 2910-nm erbium-doped fluoride glass fiber laser is a mid-infrared ablative fractional device that operates at peak water absorption. It’s designed to cause minimal residual thermal damage, resulting in less discomfort, shorter downtime, and potentially fewer side effects than conventional ablative lasers, Dr. Murray said.
Because of the way the pulses are delivered, “it’s far less painful than traditional fractional ablative lasers, so you can use mainly topical numbing; you don’t need nerve blocks, you don’t have to infiltrate lidocaine, you don’t have to put the patient under anesthesia,” she said.
“Because of the wavelength, how pulses are delivered and how customizable the settings are, it’s safer to use in darker skin types,” and the density, depth, and the amount of coagulation applied into the skin are customizable, Dr. Murray added.
The laser also delivers pulses in a different way than the conventional 2940-nm erbium and CO2 lasers, she explained. “Traditional lasers do it all in one pulse. This laser uses micropulses with relaxation time in between pulses, so the body interprets it as less painful and allows pressure and steam to escape out of the channel, which results in faster healing.”
The study patients had topical anesthetic cream applied to their faces 45-60 minutes before the procedure. Multiple passes were made using both superficial and deep laser modes. The average patient age was 65.7 years, and Fitzpatrick skin types included I (n = 3), II (n = 3), III (n = 7), and IV (n = 2). On a scale of 0-10, the average level of discomfort was 4.9, and the average patient satisfaction after three treatments was 4.8, Dr. Murray said.
For cosmetic improvement, the study used the 5-point Global Aesthetic Improvement Scale (GAIS). Blinded reviewers evaluated digital images and determined an average GAIS score of 3.2 for overall appearance, 2.9 for wrinkles, 3.6 for pigment, 3.1 for skin texture, and 2.6 for skin laxity.
When the patients themselves reviewed the digital images, the average GAIS score was 3.8 for overall appearance.
Side effects, said Dr. Murray, were transient, with edema and soft-tissue crusting lasting 3-5 days and erythema resolving in 1-2 weeks on average. One case of postinflammatory hyperpigmentation (PIH) did arise, which was linked to allergic contact dermatitis from the healing ointment. That patient stayed in the study and had complete resolution of the PIH.
Study Stands Out
A number of studies of the 2910-nm erbium-doped fluoride glass fiber laser have emerged over the past half year, Ritu Swali, MD, who was an American Society of Dermatologic Surgery fellow at a practice in Houston, said in an interview at the meeting. But this one stands out because of the evidence surrounding its use.
Most people are using this laser for facial resurfacing, “and we want to know that we have a technology ... with shorter downtime and easier wound care and just more comfort,” she said.
She noted that with conventional lasers, most patients get nerve blocks and some even opt for general anesthesia. “To be able to do the levels of facial resurfacing [Dr. Murray] is doing without having to do all of that pain management is pretty amazing,” Dr. Swali added.
The speed of the procedure and the relatively short downtime are also noteworthy, she said. “The huge advantage is having so much less pain from the procedure itself, so you’re able to do it faster because they’re tolerating it so well and you’re not having to take breaks,” she said.
As for downtime, Dr. Swali added, “these patients are coming in on a Thursday and they are back up and running by Monday,” as opposed to weeks that is typical with a conventional laser. This laser platform also avoids the pigmentation problems that can come with continuing and aggressive treatment with conventional lasers, she said.
Dr. Murray disclosed relationships with Acclaro Medical, the manufacturer of the laser. Dr. Swali has no relationships to disclose.
A version of this article first appeared on Medscape.com.
BALTIMORE — A — while causing less discomfort and downtime compared with conventional fractional lasers, a small single-center study showed.
The study enrolled 15 patients who had three treatment sessions with the 2910-nm laser. “It’s highly customizable,” the study’s lead author, Taryn Murray, MD, a dermatologist at Cleveland Clinic, told this news organization. “It has a really fast time in healing compared to traditional abatable lasers; the healing time is 5-7 days vs several weeks.” Dr. Murray presented the results at the annual meeting of the American Society for Laser Medicine and Surgery (ASLMS).
The Technology Behind the Laser
The 2910-nm erbium-doped fluoride glass fiber laser is a mid-infrared ablative fractional device that operates at peak water absorption. It’s designed to cause minimal residual thermal damage, resulting in less discomfort, shorter downtime, and potentially fewer side effects than conventional ablative lasers, Dr. Murray said.
Because of the way the pulses are delivered, “it’s far less painful than traditional fractional ablative lasers, so you can use mainly topical numbing; you don’t need nerve blocks, you don’t have to infiltrate lidocaine, you don’t have to put the patient under anesthesia,” she said.
“Because of the wavelength, how pulses are delivered and how customizable the settings are, it’s safer to use in darker skin types,” and the density, depth, and the amount of coagulation applied into the skin are customizable, Dr. Murray added.
The laser also delivers pulses in a different way than the conventional 2940-nm erbium and CO2 lasers, she explained. “Traditional lasers do it all in one pulse. This laser uses micropulses with relaxation time in between pulses, so the body interprets it as less painful and allows pressure and steam to escape out of the channel, which results in faster healing.”
The study patients had topical anesthetic cream applied to their faces 45-60 minutes before the procedure. Multiple passes were made using both superficial and deep laser modes. The average patient age was 65.7 years, and Fitzpatrick skin types included I (n = 3), II (n = 3), III (n = 7), and IV (n = 2). On a scale of 0-10, the average level of discomfort was 4.9, and the average patient satisfaction after three treatments was 4.8, Dr. Murray said.
For cosmetic improvement, the study used the 5-point Global Aesthetic Improvement Scale (GAIS). Blinded reviewers evaluated digital images and determined an average GAIS score of 3.2 for overall appearance, 2.9 for wrinkles, 3.6 for pigment, 3.1 for skin texture, and 2.6 for skin laxity.
When the patients themselves reviewed the digital images, the average GAIS score was 3.8 for overall appearance.
Side effects, said Dr. Murray, were transient, with edema and soft-tissue crusting lasting 3-5 days and erythema resolving in 1-2 weeks on average. One case of postinflammatory hyperpigmentation (PIH) did arise, which was linked to allergic contact dermatitis from the healing ointment. That patient stayed in the study and had complete resolution of the PIH.
Study Stands Out
A number of studies of the 2910-nm erbium-doped fluoride glass fiber laser have emerged over the past half year, Ritu Swali, MD, who was an American Society of Dermatologic Surgery fellow at a practice in Houston, said in an interview at the meeting. But this one stands out because of the evidence surrounding its use.
Most people are using this laser for facial resurfacing, “and we want to know that we have a technology ... with shorter downtime and easier wound care and just more comfort,” she said.
She noted that with conventional lasers, most patients get nerve blocks and some even opt for general anesthesia. “To be able to do the levels of facial resurfacing [Dr. Murray] is doing without having to do all of that pain management is pretty amazing,” Dr. Swali added.
The speed of the procedure and the relatively short downtime are also noteworthy, she said. “The huge advantage is having so much less pain from the procedure itself, so you’re able to do it faster because they’re tolerating it so well and you’re not having to take breaks,” she said.
As for downtime, Dr. Swali added, “these patients are coming in on a Thursday and they are back up and running by Monday,” as opposed to weeks that is typical with a conventional laser. This laser platform also avoids the pigmentation problems that can come with continuing and aggressive treatment with conventional lasers, she said.
Dr. Murray disclosed relationships with Acclaro Medical, the manufacturer of the laser. Dr. Swali has no relationships to disclose.
A version of this article first appeared on Medscape.com.
FROM ASLMS 2024
‘We Need to Rethink Our Options’: Lung Cancer Recurrence
This transcript has been edited for clarity.
Hello. It’s Mark Kris reporting back after attending the New York Lung Cancer Foundation Summit here in New York. A large amount of discussion went on, but as usual, I was most interested in the perioperative space.
In previous videos, I’ve talked about this ongoing discussion of whether you should operate and give adjuvant therapy or give neoadjuvant therapy, and I’ve addressed that already. One thing I want to bring up – and as we move off of that argument, which frankly doesn’t have an answer today, with neoadjuvant therapy, having all the data to support it – is
I was taught early on by my surgical mentors that the issue here was systemic control. While they could do very successful surgery to get high levels of local control, they could not control systemic disease. Sadly, the tools we had early on with chemotherapy were just not good enough. Suddenly, we have better tools to control systemic spread. In the past, the vast majority of occurrences were systemic; they’re now local.
What I think we need to do as a group of practitioners trying to deal with the problems getting in the way of curing our patients is look at what the issue is now. Frankly, the big issue now, as systemic therapy has controlled metastatic disease, is recurrence in the chest.
We give adjuvant osimertinib. Please remember what the numbers are. In the osimertinib arm, of the 11 recurrences reported in the European Society for Medical Oncology presentation a few years back, nine of them were in the chest or mediastinal nodes. In the arm that got no osimertinib afterward, there were 46 recurrences, and 32 of those 46 recurrences were in the chest, either the lung or mediastinal nodes. Therefore, 74% of the recurrences are suddenly in the chest. What’s the issue here?
The issue is we need to find strategies to give better disease control in the chest, as we have made inroads in controlling systemic disease with the targeted therapies in the endothelial growth factor receptor space, and very likely the checkpoint inhibitors, too, as that data kind of filters out. We need to think about how better to get local control.
I think rather than continue to get into this argument of neoadjuvant vs adjuvant, we should move to what’s really hurting our patients. Again, the data I quoted you was from the ADAURA trial, which was adjuvant therapy, and I’m sure the neoadjuvant is going to show the same thing. It’s better systemic therapy but now, more trouble in the chest.
How are we going to deal with that? I’d like to throw out one strategy, and that is to rethink the role of radiation in these patients. Again, if the problem is local in the chest, lung, and lymph nodes, we have to think about local therapy. Yes, we’re not recommending it routinely for everybody, but now that we have better systemic control, we need to rethink our options. The obvious one to rethink is about giving radiotherapy.
We should also use what we learned in the earlier trials, which is that there is harm in giving excessive radiation to the heart. If you avoid the heart, you avoid the harm. We have better planning strategies for stereotactic body radiotherapy and more traditional radiation, and of course, we have proton therapy as well.
As we continue to struggle with the idea of that patient with stage II or III disease, whether to give adjuvant vs neoadjuvant therapy, please remember to consider their risk in 2024. Their risk for first recurrence is in the chest.
What are we going to do to better control disease in the chest? We have a challenge. I’m sure we can meet it if we put our heads together.
Dr. Kris is professor of medicine at Weill Cornell Medical College, and attending physician, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Hello. It’s Mark Kris reporting back after attending the New York Lung Cancer Foundation Summit here in New York. A large amount of discussion went on, but as usual, I was most interested in the perioperative space.
In previous videos, I’ve talked about this ongoing discussion of whether you should operate and give adjuvant therapy or give neoadjuvant therapy, and I’ve addressed that already. One thing I want to bring up – and as we move off of that argument, which frankly doesn’t have an answer today, with neoadjuvant therapy, having all the data to support it – is
I was taught early on by my surgical mentors that the issue here was systemic control. While they could do very successful surgery to get high levels of local control, they could not control systemic disease. Sadly, the tools we had early on with chemotherapy were just not good enough. Suddenly, we have better tools to control systemic spread. In the past, the vast majority of occurrences were systemic; they’re now local.
What I think we need to do as a group of practitioners trying to deal with the problems getting in the way of curing our patients is look at what the issue is now. Frankly, the big issue now, as systemic therapy has controlled metastatic disease, is recurrence in the chest.
We give adjuvant osimertinib. Please remember what the numbers are. In the osimertinib arm, of the 11 recurrences reported in the European Society for Medical Oncology presentation a few years back, nine of them were in the chest or mediastinal nodes. In the arm that got no osimertinib afterward, there were 46 recurrences, and 32 of those 46 recurrences were in the chest, either the lung or mediastinal nodes. Therefore, 74% of the recurrences are suddenly in the chest. What’s the issue here?
The issue is we need to find strategies to give better disease control in the chest, as we have made inroads in controlling systemic disease with the targeted therapies in the endothelial growth factor receptor space, and very likely the checkpoint inhibitors, too, as that data kind of filters out. We need to think about how better to get local control.
I think rather than continue to get into this argument of neoadjuvant vs adjuvant, we should move to what’s really hurting our patients. Again, the data I quoted you was from the ADAURA trial, which was adjuvant therapy, and I’m sure the neoadjuvant is going to show the same thing. It’s better systemic therapy but now, more trouble in the chest.
How are we going to deal with that? I’d like to throw out one strategy, and that is to rethink the role of radiation in these patients. Again, if the problem is local in the chest, lung, and lymph nodes, we have to think about local therapy. Yes, we’re not recommending it routinely for everybody, but now that we have better systemic control, we need to rethink our options. The obvious one to rethink is about giving radiotherapy.
We should also use what we learned in the earlier trials, which is that there is harm in giving excessive radiation to the heart. If you avoid the heart, you avoid the harm. We have better planning strategies for stereotactic body radiotherapy and more traditional radiation, and of course, we have proton therapy as well.
As we continue to struggle with the idea of that patient with stage II or III disease, whether to give adjuvant vs neoadjuvant therapy, please remember to consider their risk in 2024. Their risk for first recurrence is in the chest.
What are we going to do to better control disease in the chest? We have a challenge. I’m sure we can meet it if we put our heads together.
Dr. Kris is professor of medicine at Weill Cornell Medical College, and attending physician, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Hello. It’s Mark Kris reporting back after attending the New York Lung Cancer Foundation Summit here in New York. A large amount of discussion went on, but as usual, I was most interested in the perioperative space.
In previous videos, I’ve talked about this ongoing discussion of whether you should operate and give adjuvant therapy or give neoadjuvant therapy, and I’ve addressed that already. One thing I want to bring up – and as we move off of that argument, which frankly doesn’t have an answer today, with neoadjuvant therapy, having all the data to support it – is
I was taught early on by my surgical mentors that the issue here was systemic control. While they could do very successful surgery to get high levels of local control, they could not control systemic disease. Sadly, the tools we had early on with chemotherapy were just not good enough. Suddenly, we have better tools to control systemic spread. In the past, the vast majority of occurrences were systemic; they’re now local.
What I think we need to do as a group of practitioners trying to deal with the problems getting in the way of curing our patients is look at what the issue is now. Frankly, the big issue now, as systemic therapy has controlled metastatic disease, is recurrence in the chest.
We give adjuvant osimertinib. Please remember what the numbers are. In the osimertinib arm, of the 11 recurrences reported in the European Society for Medical Oncology presentation a few years back, nine of them were in the chest or mediastinal nodes. In the arm that got no osimertinib afterward, there were 46 recurrences, and 32 of those 46 recurrences were in the chest, either the lung or mediastinal nodes. Therefore, 74% of the recurrences are suddenly in the chest. What’s the issue here?
The issue is we need to find strategies to give better disease control in the chest, as we have made inroads in controlling systemic disease with the targeted therapies in the endothelial growth factor receptor space, and very likely the checkpoint inhibitors, too, as that data kind of filters out. We need to think about how better to get local control.
I think rather than continue to get into this argument of neoadjuvant vs adjuvant, we should move to what’s really hurting our patients. Again, the data I quoted you was from the ADAURA trial, which was adjuvant therapy, and I’m sure the neoadjuvant is going to show the same thing. It’s better systemic therapy but now, more trouble in the chest.
How are we going to deal with that? I’d like to throw out one strategy, and that is to rethink the role of radiation in these patients. Again, if the problem is local in the chest, lung, and lymph nodes, we have to think about local therapy. Yes, we’re not recommending it routinely for everybody, but now that we have better systemic control, we need to rethink our options. The obvious one to rethink is about giving radiotherapy.
We should also use what we learned in the earlier trials, which is that there is harm in giving excessive radiation to the heart. If you avoid the heart, you avoid the harm. We have better planning strategies for stereotactic body radiotherapy and more traditional radiation, and of course, we have proton therapy as well.
As we continue to struggle with the idea of that patient with stage II or III disease, whether to give adjuvant vs neoadjuvant therapy, please remember to consider their risk in 2024. Their risk for first recurrence is in the chest.
What are we going to do to better control disease in the chest? We have a challenge. I’m sure we can meet it if we put our heads together.
Dr. Kris is professor of medicine at Weill Cornell Medical College, and attending physician, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York. He disclosed ties with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.
A version of this article appeared on Medscape.com.
First Results From Laser-Related Adverse Events Registry Reported
BALTIMORE — A relatively . But the process of reporting AEs to the registry needs to be made easier to attract more cases and provide a more complete picture of complications after dermatologic procedures, a researcher and observer said.
The Cutaneous Procedures Adverse Events Reporting Registry (CAPER) was established in 2021 to track AEs from dermatologic procedures. Since then, it has logged a total of 81 cases and 147 AEs from 27 unique procedures, Eric Koza, MD, a postdoctoral research fellow in the Department of Dermatology at Northwestern University, Chicago, reported at the annual conference of the American Society for Laser Medicine and Surgery.
“The takeaways from this project is that 20 laser and energy device treatments have been reported to the registry, half of which were nonablative laser treatments,” Dr. Koza said in presenting the results. “Of the adverse events reported, nonphysicians and non-dermatologic physicians were more likely to be associated with severe or persistent adverse events.”
The American Society for Dermatologic Surgery Association and the Northwestern University Department of Dermatology launched CAPER. Previously, Dr. Koza said, AEs were typically reported only through the Food and Drug Administration’s AE reporting system. He noted that CAPER is the only voluntary national reporting registry for AEs from dermatologic procedures.
What the Registry Shows So Far
The registry matched 72 of the 81 cases with type of provider, with dermatologist-conducted procedures (51, 70.8%) comprising the majority, followed by nonphysician-conducted procedures (14, 19.4%) and nondermatologist physician–conducted procedures (7, 9.7%).
Of the 81 total cases, the following reports were related to laser and energy device treatments: 12 (14.3%) from nonablative laser treatments, five (6%) from light treatments, and three (3.6%) from ablative laser treatments, Dr. Koza said.
Among nonablative laser treatments, the most common AE was blistering (six reports, 50%). Scar, pain, and hypopigmentation accounted for two cases each (16.67%). Dermatologists performed seven of these cases (58.3%); nonphysicians, four (33.3%); and a non-dermatologist physician, one (8.3%).
For intense pulsed-light treatments, burns were the most common AEs (three reports, 60%), with swelling and inflammation each accounting for one case (20%). Three of these cases (75%) were confirmed to have been performed by nonphysicians.
The ablative laser treatment AEs included one case each of hypopigmentation, scar, and erythema. Two of the three cases were confirmed to have been performed by dermatologists.
Dr. Koza acknowledged the low number of cases is a limitation of this analysis of registry reports. A future goal for CAPER is to publicize it more, he said. “The registry is only 3 years old,” he told this news organization. “Hopefully, we can get more data as time goes on. We’ve been getting more and more each year.” CAPER adapted data entry forms used in other registries.
Submitting a case to the registry takes about 15 minutes of the provider’s time, Dr. Koza said. “We can streamline that to make it easier for people to submit their adverse events,” he said in an interview.
Only registry staff have access to the reports, and when reported, the data “is de-identified and any identifying information pertaining to the patient or reporter is removed,” according to a statement on the CAPER website.
‘Needs a Little Help’
Jennifer Lin, MD, a dermatologist at Brigham and Women’s Hospital and Dana-Farber Cancer Institute in Boston, who was at the meeting, commented on the onerous reporting process and the “low” enrollment. “It’s such an important initiative and with everyone over-logging e-mails, a 15-minute entry just is not going to cut it,” she told this news organization.
For providers, reporting AEs is stressful, she said. “As it is, it’s hard to voluntarily submit an adverse event,” Dr. Lin continued. “There’s a feeling of shame. Hospitals require it in order to monitor adverse events, but there’s no monitoring when you’re out in your own private practice.”
“The idea is excellent, but I think to facilitate better enrollment, the word has to get out at all these meetings” and make it easier to submit cases, Dr. Lin added. “It’s a good idea, but it needs a little help.”
Information on submitting AE reports to CAPER is available on the CAPER website.
Dr. Koza and Dr. Lin had no relevant relationships to disclose.
A version of this article first appeared on Medscape.com.
BALTIMORE — A relatively . But the process of reporting AEs to the registry needs to be made easier to attract more cases and provide a more complete picture of complications after dermatologic procedures, a researcher and observer said.
The Cutaneous Procedures Adverse Events Reporting Registry (CAPER) was established in 2021 to track AEs from dermatologic procedures. Since then, it has logged a total of 81 cases and 147 AEs from 27 unique procedures, Eric Koza, MD, a postdoctoral research fellow in the Department of Dermatology at Northwestern University, Chicago, reported at the annual conference of the American Society for Laser Medicine and Surgery.
“The takeaways from this project is that 20 laser and energy device treatments have been reported to the registry, half of which were nonablative laser treatments,” Dr. Koza said in presenting the results. “Of the adverse events reported, nonphysicians and non-dermatologic physicians were more likely to be associated with severe or persistent adverse events.”
The American Society for Dermatologic Surgery Association and the Northwestern University Department of Dermatology launched CAPER. Previously, Dr. Koza said, AEs were typically reported only through the Food and Drug Administration’s AE reporting system. He noted that CAPER is the only voluntary national reporting registry for AEs from dermatologic procedures.
What the Registry Shows So Far
The registry matched 72 of the 81 cases with type of provider, with dermatologist-conducted procedures (51, 70.8%) comprising the majority, followed by nonphysician-conducted procedures (14, 19.4%) and nondermatologist physician–conducted procedures (7, 9.7%).
Of the 81 total cases, the following reports were related to laser and energy device treatments: 12 (14.3%) from nonablative laser treatments, five (6%) from light treatments, and three (3.6%) from ablative laser treatments, Dr. Koza said.
Among nonablative laser treatments, the most common AE was blistering (six reports, 50%). Scar, pain, and hypopigmentation accounted for two cases each (16.67%). Dermatologists performed seven of these cases (58.3%); nonphysicians, four (33.3%); and a non-dermatologist physician, one (8.3%).
For intense pulsed-light treatments, burns were the most common AEs (three reports, 60%), with swelling and inflammation each accounting for one case (20%). Three of these cases (75%) were confirmed to have been performed by nonphysicians.
The ablative laser treatment AEs included one case each of hypopigmentation, scar, and erythema. Two of the three cases were confirmed to have been performed by dermatologists.
Dr. Koza acknowledged the low number of cases is a limitation of this analysis of registry reports. A future goal for CAPER is to publicize it more, he said. “The registry is only 3 years old,” he told this news organization. “Hopefully, we can get more data as time goes on. We’ve been getting more and more each year.” CAPER adapted data entry forms used in other registries.
Submitting a case to the registry takes about 15 minutes of the provider’s time, Dr. Koza said. “We can streamline that to make it easier for people to submit their adverse events,” he said in an interview.
Only registry staff have access to the reports, and when reported, the data “is de-identified and any identifying information pertaining to the patient or reporter is removed,” according to a statement on the CAPER website.
‘Needs a Little Help’
Jennifer Lin, MD, a dermatologist at Brigham and Women’s Hospital and Dana-Farber Cancer Institute in Boston, who was at the meeting, commented on the onerous reporting process and the “low” enrollment. “It’s such an important initiative and with everyone over-logging e-mails, a 15-minute entry just is not going to cut it,” she told this news organization.
For providers, reporting AEs is stressful, she said. “As it is, it’s hard to voluntarily submit an adverse event,” Dr. Lin continued. “There’s a feeling of shame. Hospitals require it in order to monitor adverse events, but there’s no monitoring when you’re out in your own private practice.”
“The idea is excellent, but I think to facilitate better enrollment, the word has to get out at all these meetings” and make it easier to submit cases, Dr. Lin added. “It’s a good idea, but it needs a little help.”
Information on submitting AE reports to CAPER is available on the CAPER website.
Dr. Koza and Dr. Lin had no relevant relationships to disclose.
A version of this article first appeared on Medscape.com.
BALTIMORE — A relatively . But the process of reporting AEs to the registry needs to be made easier to attract more cases and provide a more complete picture of complications after dermatologic procedures, a researcher and observer said.
The Cutaneous Procedures Adverse Events Reporting Registry (CAPER) was established in 2021 to track AEs from dermatologic procedures. Since then, it has logged a total of 81 cases and 147 AEs from 27 unique procedures, Eric Koza, MD, a postdoctoral research fellow in the Department of Dermatology at Northwestern University, Chicago, reported at the annual conference of the American Society for Laser Medicine and Surgery.
“The takeaways from this project is that 20 laser and energy device treatments have been reported to the registry, half of which were nonablative laser treatments,” Dr. Koza said in presenting the results. “Of the adverse events reported, nonphysicians and non-dermatologic physicians were more likely to be associated with severe or persistent adverse events.”
The American Society for Dermatologic Surgery Association and the Northwestern University Department of Dermatology launched CAPER. Previously, Dr. Koza said, AEs were typically reported only through the Food and Drug Administration’s AE reporting system. He noted that CAPER is the only voluntary national reporting registry for AEs from dermatologic procedures.
What the Registry Shows So Far
The registry matched 72 of the 81 cases with type of provider, with dermatologist-conducted procedures (51, 70.8%) comprising the majority, followed by nonphysician-conducted procedures (14, 19.4%) and nondermatologist physician–conducted procedures (7, 9.7%).
Of the 81 total cases, the following reports were related to laser and energy device treatments: 12 (14.3%) from nonablative laser treatments, five (6%) from light treatments, and three (3.6%) from ablative laser treatments, Dr. Koza said.
Among nonablative laser treatments, the most common AE was blistering (six reports, 50%). Scar, pain, and hypopigmentation accounted for two cases each (16.67%). Dermatologists performed seven of these cases (58.3%); nonphysicians, four (33.3%); and a non-dermatologist physician, one (8.3%).
For intense pulsed-light treatments, burns were the most common AEs (three reports, 60%), with swelling and inflammation each accounting for one case (20%). Three of these cases (75%) were confirmed to have been performed by nonphysicians.
The ablative laser treatment AEs included one case each of hypopigmentation, scar, and erythema. Two of the three cases were confirmed to have been performed by dermatologists.
Dr. Koza acknowledged the low number of cases is a limitation of this analysis of registry reports. A future goal for CAPER is to publicize it more, he said. “The registry is only 3 years old,” he told this news organization. “Hopefully, we can get more data as time goes on. We’ve been getting more and more each year.” CAPER adapted data entry forms used in other registries.
Submitting a case to the registry takes about 15 minutes of the provider’s time, Dr. Koza said. “We can streamline that to make it easier for people to submit their adverse events,” he said in an interview.
Only registry staff have access to the reports, and when reported, the data “is de-identified and any identifying information pertaining to the patient or reporter is removed,” according to a statement on the CAPER website.
‘Needs a Little Help’
Jennifer Lin, MD, a dermatologist at Brigham and Women’s Hospital and Dana-Farber Cancer Institute in Boston, who was at the meeting, commented on the onerous reporting process and the “low” enrollment. “It’s such an important initiative and with everyone over-logging e-mails, a 15-minute entry just is not going to cut it,” she told this news organization.
For providers, reporting AEs is stressful, she said. “As it is, it’s hard to voluntarily submit an adverse event,” Dr. Lin continued. “There’s a feeling of shame. Hospitals require it in order to monitor adverse events, but there’s no monitoring when you’re out in your own private practice.”
“The idea is excellent, but I think to facilitate better enrollment, the word has to get out at all these meetings” and make it easier to submit cases, Dr. Lin added. “It’s a good idea, but it needs a little help.”
Information on submitting AE reports to CAPER is available on the CAPER website.
Dr. Koza and Dr. Lin had no relevant relationships to disclose.
A version of this article first appeared on Medscape.com.
FROM ASLMS 2024
A Welcome Trade-off
At the end of March, in an anniversary no one but I noticed, I passed 4 years since I’d last rounded at the hospital.
It’s hard to comprehend that. I was at the hospital regularly for the first 22 years of my career, though admittedly it had dwindled from daily (1998-2011) to 1-2 weekends a month at the end.
Looking back, I still don’t miss it, and have no desire to go back. That’s not to say I don’t keep up on inpatient neurology, in case circumstances change, but at this point, honestly, I don’t want to. I’ve become accustomed to my non-hospital world, no late-night consults, no weekends spent rounding, no taking separate cars to restaurants or family events in case I get called in.
There are certainly things I miss about it. As odd as it may seem (and as much as I’d complain about it) I liked the wee hours of the really late night and early morning. It was quieter. Less chasing patients to tests or therapy. Pleasant idle chatter with staff and the few others docs around. Sitting at the computer and trying to think out a case on the fly. There was always junk food lying around.
But at this point in my life I’ll take the quiet of being home and my routine office hours. I know when my office day starts and ends. Aside from the occasional stop at Costco, I won’t be going anywhere else on my way home. I still get the occasional after-hours call, but none that require me to run to the ER.
On Fridays I’m glad the week is over, and don’t dread the 5:00 answering service switchover, or my call partner giving me the patient list.
There’s some revenue lost in the deal, but I’ll still take the trade-off.
It’s not like I ever had some grand plan to leave the hospital — I actually had thought I’d be there, at least occasionally, until retirement. But here I am.
Not to say there aren’t docs my age (and older) who still do it. Certainly our experience makes us good at it. But younger docs are closer to residency, which is primarily inpatient, so it’s an easier transition for many.
They probably have more energy, too.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
At the end of March, in an anniversary no one but I noticed, I passed 4 years since I’d last rounded at the hospital.
It’s hard to comprehend that. I was at the hospital regularly for the first 22 years of my career, though admittedly it had dwindled from daily (1998-2011) to 1-2 weekends a month at the end.
Looking back, I still don’t miss it, and have no desire to go back. That’s not to say I don’t keep up on inpatient neurology, in case circumstances change, but at this point, honestly, I don’t want to. I’ve become accustomed to my non-hospital world, no late-night consults, no weekends spent rounding, no taking separate cars to restaurants or family events in case I get called in.
There are certainly things I miss about it. As odd as it may seem (and as much as I’d complain about it) I liked the wee hours of the really late night and early morning. It was quieter. Less chasing patients to tests or therapy. Pleasant idle chatter with staff and the few others docs around. Sitting at the computer and trying to think out a case on the fly. There was always junk food lying around.
But at this point in my life I’ll take the quiet of being home and my routine office hours. I know when my office day starts and ends. Aside from the occasional stop at Costco, I won’t be going anywhere else on my way home. I still get the occasional after-hours call, but none that require me to run to the ER.
On Fridays I’m glad the week is over, and don’t dread the 5:00 answering service switchover, or my call partner giving me the patient list.
There’s some revenue lost in the deal, but I’ll still take the trade-off.
It’s not like I ever had some grand plan to leave the hospital — I actually had thought I’d be there, at least occasionally, until retirement. But here I am.
Not to say there aren’t docs my age (and older) who still do it. Certainly our experience makes us good at it. But younger docs are closer to residency, which is primarily inpatient, so it’s an easier transition for many.
They probably have more energy, too.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
At the end of March, in an anniversary no one but I noticed, I passed 4 years since I’d last rounded at the hospital.
It’s hard to comprehend that. I was at the hospital regularly for the first 22 years of my career, though admittedly it had dwindled from daily (1998-2011) to 1-2 weekends a month at the end.
Looking back, I still don’t miss it, and have no desire to go back. That’s not to say I don’t keep up on inpatient neurology, in case circumstances change, but at this point, honestly, I don’t want to. I’ve become accustomed to my non-hospital world, no late-night consults, no weekends spent rounding, no taking separate cars to restaurants or family events in case I get called in.
There are certainly things I miss about it. As odd as it may seem (and as much as I’d complain about it) I liked the wee hours of the really late night and early morning. It was quieter. Less chasing patients to tests or therapy. Pleasant idle chatter with staff and the few others docs around. Sitting at the computer and trying to think out a case on the fly. There was always junk food lying around.
But at this point in my life I’ll take the quiet of being home and my routine office hours. I know when my office day starts and ends. Aside from the occasional stop at Costco, I won’t be going anywhere else on my way home. I still get the occasional after-hours call, but none that require me to run to the ER.
On Fridays I’m glad the week is over, and don’t dread the 5:00 answering service switchover, or my call partner giving me the patient list.
There’s some revenue lost in the deal, but I’ll still take the trade-off.
It’s not like I ever had some grand plan to leave the hospital — I actually had thought I’d be there, at least occasionally, until retirement. But here I am.
Not to say there aren’t docs my age (and older) who still do it. Certainly our experience makes us good at it. But younger docs are closer to residency, which is primarily inpatient, so it’s an easier transition for many.
They probably have more energy, too.
Dr. Block has a solo neurology practice in Scottsdale, Arizona.
Commentary: Comparisons Among PsA Therapies, May 2024
Bimekizumab is a novel biologic therapy that inhibits interleukin (IL)–17A and IL-17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. In the absence of a formal head-to-head study, matching-adjusted indirect comparison is a method to evaluate comparative effectiveness. Warren and colleagues ran a study that included biological DMARD-naive patients and patients with inadequate response to tumor necrosis factor inhibitors (TNFi-IR) with PsA who received bimekizumab (160 mg every 4 weeks; 431 and 267 patients, respectively) and guselkumab (100 mg every 4 weeks or every 8 weeks; 495 and 189 patients, respectively). They demonstrate that in biological DMARD-naive patients, bimekizumab was associated with a greater likelihood of achieving ≥70% improvement in American College of Rheumatology (ACR) response and minimal disease activity outcome at week 52 compared with guselkumab. Similar outcomes were observed in the TNFi-IR subgroup. Thus, bimekizumab may be more effective than guselkumab in PsA. Formal head-to-head studies comparing bimekizumab vs guselkumab are required.
With the availability of multiple targeted therapies for PsA, choosing the most effective and safe drug for a patient is difficult, especially in the absence of many head-to-head clinical trials. To help address this problem, Lin and Ren conducted a network meta-analysis of head-to-head active comparison studies in PsA. They included 17 studies in their analysis and demonstrated that Janus kinase inhibitors had the highest probability of achieving ACR 20/50/70 response. Treatment with IL-17A inhibitors was more likely than TNFi therapy to lead to resolution of enthesitis and dactylitis and achieving combined ACR 50 and Psoriasis Area Severity Index 100 response. Patients receiving phosphodiesterase 4 inhibitors were least likely to have adverse events. They conclude that when both efficacy and safety are considered, IL-17A inhibitors may be the better agent for initial therapy for PsA. IL-17A inhibitors are indeed safe and efficacious in PsA; more direct head-to-head comparisons as well as strategy trials are required to determine choice of first and subsequent therapy in PsA.
Infections are the most important adverse effects of targeted therapies. The risk for infection in PsA in real-world settings is not well known. In a cohort study that included 12,071 patients with PsA from the French national health insurance database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib), Bastard and colleagues demonstrated that the incidence of serious infections in users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93). Thus, the overall risk for serious infections is low, with etanercept and ustekinumab being safer treatment options than adalimumab.
Bimekizumab is a novel biologic therapy that inhibits interleukin (IL)–17A and IL-17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. In the absence of a formal head-to-head study, matching-adjusted indirect comparison is a method to evaluate comparative effectiveness. Warren and colleagues ran a study that included biological DMARD-naive patients and patients with inadequate response to tumor necrosis factor inhibitors (TNFi-IR) with PsA who received bimekizumab (160 mg every 4 weeks; 431 and 267 patients, respectively) and guselkumab (100 mg every 4 weeks or every 8 weeks; 495 and 189 patients, respectively). They demonstrate that in biological DMARD-naive patients, bimekizumab was associated with a greater likelihood of achieving ≥70% improvement in American College of Rheumatology (ACR) response and minimal disease activity outcome at week 52 compared with guselkumab. Similar outcomes were observed in the TNFi-IR subgroup. Thus, bimekizumab may be more effective than guselkumab in PsA. Formal head-to-head studies comparing bimekizumab vs guselkumab are required.
With the availability of multiple targeted therapies for PsA, choosing the most effective and safe drug for a patient is difficult, especially in the absence of many head-to-head clinical trials. To help address this problem, Lin and Ren conducted a network meta-analysis of head-to-head active comparison studies in PsA. They included 17 studies in their analysis and demonstrated that Janus kinase inhibitors had the highest probability of achieving ACR 20/50/70 response. Treatment with IL-17A inhibitors was more likely than TNFi therapy to lead to resolution of enthesitis and dactylitis and achieving combined ACR 50 and Psoriasis Area Severity Index 100 response. Patients receiving phosphodiesterase 4 inhibitors were least likely to have adverse events. They conclude that when both efficacy and safety are considered, IL-17A inhibitors may be the better agent for initial therapy for PsA. IL-17A inhibitors are indeed safe and efficacious in PsA; more direct head-to-head comparisons as well as strategy trials are required to determine choice of first and subsequent therapy in PsA.
Infections are the most important adverse effects of targeted therapies. The risk for infection in PsA in real-world settings is not well known. In a cohort study that included 12,071 patients with PsA from the French national health insurance database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib), Bastard and colleagues demonstrated that the incidence of serious infections in users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93). Thus, the overall risk for serious infections is low, with etanercept and ustekinumab being safer treatment options than adalimumab.
Bimekizumab is a novel biologic therapy that inhibits interleukin (IL)–17A and IL-17F and is efficacious in the treatment of psoriasis, PsA, and axial spondyloarthritis. In the absence of a formal head-to-head study, matching-adjusted indirect comparison is a method to evaluate comparative effectiveness. Warren and colleagues ran a study that included biological DMARD-naive patients and patients with inadequate response to tumor necrosis factor inhibitors (TNFi-IR) with PsA who received bimekizumab (160 mg every 4 weeks; 431 and 267 patients, respectively) and guselkumab (100 mg every 4 weeks or every 8 weeks; 495 and 189 patients, respectively). They demonstrate that in biological DMARD-naive patients, bimekizumab was associated with a greater likelihood of achieving ≥70% improvement in American College of Rheumatology (ACR) response and minimal disease activity outcome at week 52 compared with guselkumab. Similar outcomes were observed in the TNFi-IR subgroup. Thus, bimekizumab may be more effective than guselkumab in PsA. Formal head-to-head studies comparing bimekizumab vs guselkumab are required.
With the availability of multiple targeted therapies for PsA, choosing the most effective and safe drug for a patient is difficult, especially in the absence of many head-to-head clinical trials. To help address this problem, Lin and Ren conducted a network meta-analysis of head-to-head active comparison studies in PsA. They included 17 studies in their analysis and demonstrated that Janus kinase inhibitors had the highest probability of achieving ACR 20/50/70 response. Treatment with IL-17A inhibitors was more likely than TNFi therapy to lead to resolution of enthesitis and dactylitis and achieving combined ACR 50 and Psoriasis Area Severity Index 100 response. Patients receiving phosphodiesterase 4 inhibitors were least likely to have adverse events. They conclude that when both efficacy and safety are considered, IL-17A inhibitors may be the better agent for initial therapy for PsA. IL-17A inhibitors are indeed safe and efficacious in PsA; more direct head-to-head comparisons as well as strategy trials are required to determine choice of first and subsequent therapy in PsA.
Infections are the most important adverse effects of targeted therapies. The risk for infection in PsA in real-world settings is not well known. In a cohort study that included 12,071 patients with PsA from the French national health insurance database who were new users of targeted therapies (adalimumab, etanercept, golimumab, certolizumab pegol, infliximab, secukinumab, ixekizumab, ustekinumab, and tofacitinib), Bastard and colleagues demonstrated that the incidence of serious infections in users of targeted therapies was 17.0 per 1000 person-years. Compared with new users of adalimumab, the risk for serious infections was significantly lower in new users of etanercept (weighted hazard ratio [wHR] 0.72; 95% CI 0.53-0.97) and ustekinumab (wHR 0.57; 95% CI 0.35-0.93). Thus, the overall risk for serious infections is low, with etanercept and ustekinumab being safer treatment options than adalimumab.