MDedge Rheumatology

Long COVID can exacerbate existing mental health disorders or cause new-onset psychiatric symptoms, but mental illness does not cause long COVID, experts say.

The consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, was published online in Physical Medicine and Rehabilitation, the journal of the American Academy of Physical Medicine and Rehabilitation (AAPM&R).

The statement was developed by a task force that included experts from physical medicine, neurology, neuropsychiatry, neuropsychology, rehabilitation psychology, and primary care. It is the eighth guidance statement on long COVID published by AAPM&R).

“Many of our patients have reported experiences in which their symptoms of long COVID have been dismissed either by loved ones in the community, or also amongst health care providers, and they’ve been told their symptoms are in their head or due to a mental health condition, but that’s simply not true,” Abby L. Cheng, MD, a physiatrist at Barnes Jewish Hospital in St. Louis and a coauthor of the new guidance, said in a press briefing.

“Long COVID is real, and mental health conditions do not cause long COVID,” Dr. Cheng added.
 

Millions of Americans affected

Anxiety and depression have been reported as the second and third most common symptoms of long COVID, according to the guidance statement.

There is some evidence that the body’s inflammatory response – specifically, circulating cytokines – may contribute to the worsening of mental health symptoms or may bring on new symptoms of anxiety or depression, said Dr. Cheng. Cytokines may also affect levels of brain chemicals, such as serotonin, she said.

Researchers are also exploring whether the persistence of virus in the body, miniature blood clots in the body and brain, and changes to the gut microbiome affect the mental health of people with long COVID.

Some mental health symptoms – such as fatigue, brain fog, sleep disturbances, and tachycardia – can mimic long COVID symptoms, said Dr. Cheng.

The treatment is the same for someone with or without long COVID who has anxiety, depression, posttraumatic stress disorder, or other mental health conditions and includes treatment of coexisting medical conditions, supportive therapy and cognitive-behavioral therapy, and pharmacologic interventions, she said.

“Group therapy may have a particular role in the long COVID population because it really provides that social connection and awareness of additional resources in addition to validation of their experiences,” Dr. Cheng said.

The guidance suggests that primary care practitioners – if it’s within their comfort zone and they have the training – can be the first line for managing mental health symptoms.

But for patients whose symptoms are interfering with functioning and their ability to interact with the community, the guidance urges primary care clinicians to refer the patient to a specialist.

“It leaves the door open to them to practice within their scope but also gives guidance as to how, why, and who should be referred to the next level of care,” said Dr. Cheng.

Coauthor Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine at UT Health San Antonio, Texas, said that although fewer people are now getting long COVID, “it’s still an impactful number.”

The Centers for Disease Control and Prevention recently estimated that about 7% of American adults (18 million) and 1.3% of children had experienced long COVID.

Dr. Gutierrez said that it’s an evolving number, as some patients who have a second or third or fourth SARS-CoV-2 infection experience exacerbations of previous bouts of long COVID or develop long COVID for the first time.

“We are still getting new patients on a regular basis with long COVID,” said AAPM&R President Steven R. Flanagan, MD, a physical medicine specialist.

“This is a problem that really is not going away. It is still real and still ever-present,” said Dr. Flanagan, chair of rehabilitation medicine at NYU Langone Health.
 

A version of this article first appeared on Medscape.com.

Long COVID can exacerbate existing mental health disorders or cause new-onset psychiatric symptoms, but mental illness does not cause long COVID, experts say.

The consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, was published online in Physical Medicine and Rehabilitation, the journal of the American Academy of Physical Medicine and Rehabilitation (AAPM&R).

The statement was developed by a task force that included experts from physical medicine, neurology, neuropsychiatry, neuropsychology, rehabilitation psychology, and primary care. It is the eighth guidance statement on long COVID published by AAPM&R).

“Many of our patients have reported experiences in which their symptoms of long COVID have been dismissed either by loved ones in the community, or also amongst health care providers, and they’ve been told their symptoms are in their head or due to a mental health condition, but that’s simply not true,” Abby L. Cheng, MD, a physiatrist at Barnes Jewish Hospital in St. Louis and a coauthor of the new guidance, said in a press briefing.

“Long COVID is real, and mental health conditions do not cause long COVID,” Dr. Cheng added.
 

Millions of Americans affected

Anxiety and depression have been reported as the second and third most common symptoms of long COVID, according to the guidance statement.

There is some evidence that the body’s inflammatory response – specifically, circulating cytokines – may contribute to the worsening of mental health symptoms or may bring on new symptoms of anxiety or depression, said Dr. Cheng. Cytokines may also affect levels of brain chemicals, such as serotonin, she said.

Researchers are also exploring whether the persistence of virus in the body, miniature blood clots in the body and brain, and changes to the gut microbiome affect the mental health of people with long COVID.

Some mental health symptoms – such as fatigue, brain fog, sleep disturbances, and tachycardia – can mimic long COVID symptoms, said Dr. Cheng.

The treatment is the same for someone with or without long COVID who has anxiety, depression, posttraumatic stress disorder, or other mental health conditions and includes treatment of coexisting medical conditions, supportive therapy and cognitive-behavioral therapy, and pharmacologic interventions, she said.

“Group therapy may have a particular role in the long COVID population because it really provides that social connection and awareness of additional resources in addition to validation of their experiences,” Dr. Cheng said.

The guidance suggests that primary care practitioners – if it’s within their comfort zone and they have the training – can be the first line for managing mental health symptoms.

But for patients whose symptoms are interfering with functioning and their ability to interact with the community, the guidance urges primary care clinicians to refer the patient to a specialist.

“It leaves the door open to them to practice within their scope but also gives guidance as to how, why, and who should be referred to the next level of care,” said Dr. Cheng.

Coauthor Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine at UT Health San Antonio, Texas, said that although fewer people are now getting long COVID, “it’s still an impactful number.”

The Centers for Disease Control and Prevention recently estimated that about 7% of American adults (18 million) and 1.3% of children had experienced long COVID.

Dr. Gutierrez said that it’s an evolving number, as some patients who have a second or third or fourth SARS-CoV-2 infection experience exacerbations of previous bouts of long COVID or develop long COVID for the first time.

“We are still getting new patients on a regular basis with long COVID,” said AAPM&R President Steven R. Flanagan, MD, a physical medicine specialist.

“This is a problem that really is not going away. It is still real and still ever-present,” said Dr. Flanagan, chair of rehabilitation medicine at NYU Langone Health.
 

A version of this article first appeared on Medscape.com.

Long COVID can exacerbate existing mental health disorders or cause new-onset psychiatric symptoms, but mental illness does not cause long COVID, experts say.

The consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, was published online in Physical Medicine and Rehabilitation, the journal of the American Academy of Physical Medicine and Rehabilitation (AAPM&R).

The statement was developed by a task force that included experts from physical medicine, neurology, neuropsychiatry, neuropsychology, rehabilitation psychology, and primary care. It is the eighth guidance statement on long COVID published by AAPM&R).

“Many of our patients have reported experiences in which their symptoms of long COVID have been dismissed either by loved ones in the community, or also amongst health care providers, and they’ve been told their symptoms are in their head or due to a mental health condition, but that’s simply not true,” Abby L. Cheng, MD, a physiatrist at Barnes Jewish Hospital in St. Louis and a coauthor of the new guidance, said in a press briefing.

“Long COVID is real, and mental health conditions do not cause long COVID,” Dr. Cheng added.
 

Millions of Americans affected

Anxiety and depression have been reported as the second and third most common symptoms of long COVID, according to the guidance statement.

There is some evidence that the body’s inflammatory response – specifically, circulating cytokines – may contribute to the worsening of mental health symptoms or may bring on new symptoms of anxiety or depression, said Dr. Cheng. Cytokines may also affect levels of brain chemicals, such as serotonin, she said.

Researchers are also exploring whether the persistence of virus in the body, miniature blood clots in the body and brain, and changes to the gut microbiome affect the mental health of people with long COVID.

Some mental health symptoms – such as fatigue, brain fog, sleep disturbances, and tachycardia – can mimic long COVID symptoms, said Dr. Cheng.

The treatment is the same for someone with or without long COVID who has anxiety, depression, posttraumatic stress disorder, or other mental health conditions and includes treatment of coexisting medical conditions, supportive therapy and cognitive-behavioral therapy, and pharmacologic interventions, she said.

“Group therapy may have a particular role in the long COVID population because it really provides that social connection and awareness of additional resources in addition to validation of their experiences,” Dr. Cheng said.

The guidance suggests that primary care practitioners – if it’s within their comfort zone and they have the training – can be the first line for managing mental health symptoms.

But for patients whose symptoms are interfering with functioning and their ability to interact with the community, the guidance urges primary care clinicians to refer the patient to a specialist.

“It leaves the door open to them to practice within their scope but also gives guidance as to how, why, and who should be referred to the next level of care,” said Dr. Cheng.

Coauthor Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine at UT Health San Antonio, Texas, said that although fewer people are now getting long COVID, “it’s still an impactful number.”

The Centers for Disease Control and Prevention recently estimated that about 7% of American adults (18 million) and 1.3% of children had experienced long COVID.

Dr. Gutierrez said that it’s an evolving number, as some patients who have a second or third or fourth SARS-CoV-2 infection experience exacerbations of previous bouts of long COVID or develop long COVID for the first time.

“We are still getting new patients on a regular basis with long COVID,” said AAPM&R President Steven R. Flanagan, MD, a physical medicine specialist.

“This is a problem that really is not going away. It is still real and still ever-present,” said Dr. Flanagan, chair of rehabilitation medicine at NYU Langone Health.
 

A version of this article first appeared on Medscape.com.

LA JOLLA, Calif. – A new analysis suggests that it may not be necessary to delay urate-lowering therapy (ULT) in gout flares, and a study warns of the potential heightened risk of peripheral arterial disease (PAD) in gout.

The reports were released at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).

The urate-lowering report, a systematic review and meta-analysis, suggests that the use of ULT during a gout flare “does not affect flare severity nor the duration of the flare or risk of recurrence in the subsequent month,” lead author Vicky Tai, MBChB, of the University of Auckland (New Zealand), said in a presentation.

She noted that there’s ongoing debate about whether ULT should be delayed until a week or two after gout flares subside to avoid their return. “This is reflected in guidelines on gout management, which have provided inconsistent recommendations on the issue,” Dr. Tai said.

As she noted, the American College of Rheumatology’s 2020 gout guidelines conditionally recommended starting ULT during gout flares – and not afterward – if it’s indicated. (The guidelines also conditionally recommend against ULT in a first gout flare, however, with a few exceptions.)

The British Society for Rheumatology’s 2017 gout guidelines suggested waiting until flares have settled down and “the patient was no longer in pain,” although ULT may be started in patients with frequent attacks. The European Alliance of Associations for Rheumatology’s gout guidelines from 2016 didn’t address timing, Dr. Tai said.

For the new analysis, Dr. Tai and colleagues examined six randomized studies from the United States (two), China (two), Taiwan (one), and Thailand (one) that examined the use of allopurinol (three studies), febuxostat (two studies), and probenecid (one). The studies, dated from 2012 to 2023, randomized 226 subjects with gout to early initiation of ULT vs. 219 who received placebo or delayed ULT. Subjects were tracked for a median of 28 days (15 days to 12 weeks).

Three of the studies were deemed to have high risk of bias.

There were no differences in patient-rated pain scores at various time points, duration of gout flares (examined in three studies), or recurrence of gout flares (examined in four studies).

“Other outcomes of interest, including long-term adherence, time to achieve target serum urate, and patient satisfaction with treatment, were not examined,” Dr. Tai said. “Adverse events were similar between groups.”

She cautioned that the sample sizes are small, and the findings may not be applicable to patients with tophaceous gout or comorbid renal disease.

A similar meta-analysis published in 2022 examined five studies (including three of those in the new analysis); among the five was one study from 1987 that examined azapropazone and indomethacin plus allopurinol. The review found “that initiation of ULT during an acute gout flare did not prolong the duration of acute flares.”
 

Risk for PAD

In the other study, researchers raised an alarm after finding a high rate of PAD in patients with gout regardless of whether they also had diabetes, which is a known risk factor for PAD. “Our data suggest that gout is an underrecognized risk factor for PAD and indicates the importance of assessing for PAD in gout patients,” lead author Nicole Leung, MD, of NYU Langone Health, said in a presentation.

According to Dr. Leung, there’s little known about links between PAD and gout, although she highlighted a 2018 study that found that patients with obstructive coronary artery disease were more likely to have poor outcomes if they also developed gout after catheterization. She highlighted a 2022 study that found higher rates of lower-extremity amputations in patients with gout independent of cardiovascular disease and diabetes. However, she noted that a link to PAD is unclear, and the study found a link between gout and amputations that was independent of PAD.

Patients with gout, she added, are not routinely screened for PAD.

For the new retrospective, cross-sectional analysis, Dr. Leung and colleagues examined Veterans Administration data from 2014 to 2018 for 7.2 million patients. The population was largely male.

Of those, 140,862 (2.52%) – the control group – had no gout or diabetes. In comparison, 11,449 (5.56%) of 205,904 with gout but not diabetes had PAD, for a rate 2.2 times greater than the control group). PAD occurred in 101,582 (8.70%) of 1,168,138 with diabetes but not gout, giving a rate 3.2 times greater than the control group. The rate was highest among people with both gout and diabetes, at 9.97% (9,905 of 99,377), which is about four times greater than the control group.

The link between gout and PAD remained after adjustment for creatinine levels, age, gender, and body mass index. Diabetes was linked to a higher risk for PAD than was gout, and the effect of both conditions combined was “less than additive.” This “may suggest an overlap and pathophysiology between the two,” she said.

Disclosure information was not provided. The Rheumatology Research Foundation funded the PAD study; funding information for the ULT/gout flare analysis was not provided.

LA JOLLA, Calif. – A new analysis suggests that it may not be necessary to delay urate-lowering therapy (ULT) in gout flares, and a study warns of the potential heightened risk of peripheral arterial disease (PAD) in gout.

The reports were released at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).

The urate-lowering report, a systematic review and meta-analysis, suggests that the use of ULT during a gout flare “does not affect flare severity nor the duration of the flare or risk of recurrence in the subsequent month,” lead author Vicky Tai, MBChB, of the University of Auckland (New Zealand), said in a presentation.

She noted that there’s ongoing debate about whether ULT should be delayed until a week or two after gout flares subside to avoid their return. “This is reflected in guidelines on gout management, which have provided inconsistent recommendations on the issue,” Dr. Tai said.

As she noted, the American College of Rheumatology’s 2020 gout guidelines conditionally recommended starting ULT during gout flares – and not afterward – if it’s indicated. (The guidelines also conditionally recommend against ULT in a first gout flare, however, with a few exceptions.)

The British Society for Rheumatology’s 2017 gout guidelines suggested waiting until flares have settled down and “the patient was no longer in pain,” although ULT may be started in patients with frequent attacks. The European Alliance of Associations for Rheumatology’s gout guidelines from 2016 didn’t address timing, Dr. Tai said.

For the new analysis, Dr. Tai and colleagues examined six randomized studies from the United States (two), China (two), Taiwan (one), and Thailand (one) that examined the use of allopurinol (three studies), febuxostat (two studies), and probenecid (one). The studies, dated from 2012 to 2023, randomized 226 subjects with gout to early initiation of ULT vs. 219 who received placebo or delayed ULT. Subjects were tracked for a median of 28 days (15 days to 12 weeks).

Three of the studies were deemed to have high risk of bias.

There were no differences in patient-rated pain scores at various time points, duration of gout flares (examined in three studies), or recurrence of gout flares (examined in four studies).

“Other outcomes of interest, including long-term adherence, time to achieve target serum urate, and patient satisfaction with treatment, were not examined,” Dr. Tai said. “Adverse events were similar between groups.”

She cautioned that the sample sizes are small, and the findings may not be applicable to patients with tophaceous gout or comorbid renal disease.

A similar meta-analysis published in 2022 examined five studies (including three of those in the new analysis); among the five was one study from 1987 that examined azapropazone and indomethacin plus allopurinol. The review found “that initiation of ULT during an acute gout flare did not prolong the duration of acute flares.”
 

Risk for PAD

In the other study, researchers raised an alarm after finding a high rate of PAD in patients with gout regardless of whether they also had diabetes, which is a known risk factor for PAD. “Our data suggest that gout is an underrecognized risk factor for PAD and indicates the importance of assessing for PAD in gout patients,” lead author Nicole Leung, MD, of NYU Langone Health, said in a presentation.

According to Dr. Leung, there’s little known about links between PAD and gout, although she highlighted a 2018 study that found that patients with obstructive coronary artery disease were more likely to have poor outcomes if they also developed gout after catheterization. She highlighted a 2022 study that found higher rates of lower-extremity amputations in patients with gout independent of cardiovascular disease and diabetes. However, she noted that a link to PAD is unclear, and the study found a link between gout and amputations that was independent of PAD.

Patients with gout, she added, are not routinely screened for PAD.

For the new retrospective, cross-sectional analysis, Dr. Leung and colleagues examined Veterans Administration data from 2014 to 2018 for 7.2 million patients. The population was largely male.

Of those, 140,862 (2.52%) – the control group – had no gout or diabetes. In comparison, 11,449 (5.56%) of 205,904 with gout but not diabetes had PAD, for a rate 2.2 times greater than the control group). PAD occurred in 101,582 (8.70%) of 1,168,138 with diabetes but not gout, giving a rate 3.2 times greater than the control group. The rate was highest among people with both gout and diabetes, at 9.97% (9,905 of 99,377), which is about four times greater than the control group.

The link between gout and PAD remained after adjustment for creatinine levels, age, gender, and body mass index. Diabetes was linked to a higher risk for PAD than was gout, and the effect of both conditions combined was “less than additive.” This “may suggest an overlap and pathophysiology between the two,” she said.

Disclosure information was not provided. The Rheumatology Research Foundation funded the PAD study; funding information for the ULT/gout flare analysis was not provided.

LA JOLLA, Calif. – A new analysis suggests that it may not be necessary to delay urate-lowering therapy (ULT) in gout flares, and a study warns of the potential heightened risk of peripheral arterial disease (PAD) in gout.

The reports were released at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network (G-CAN).

The urate-lowering report, a systematic review and meta-analysis, suggests that the use of ULT during a gout flare “does not affect flare severity nor the duration of the flare or risk of recurrence in the subsequent month,” lead author Vicky Tai, MBChB, of the University of Auckland (New Zealand), said in a presentation.

She noted that there’s ongoing debate about whether ULT should be delayed until a week or two after gout flares subside to avoid their return. “This is reflected in guidelines on gout management, which have provided inconsistent recommendations on the issue,” Dr. Tai said.

As she noted, the American College of Rheumatology’s 2020 gout guidelines conditionally recommended starting ULT during gout flares – and not afterward – if it’s indicated. (The guidelines also conditionally recommend against ULT in a first gout flare, however, with a few exceptions.)

The British Society for Rheumatology’s 2017 gout guidelines suggested waiting until flares have settled down and “the patient was no longer in pain,” although ULT may be started in patients with frequent attacks. The European Alliance of Associations for Rheumatology’s gout guidelines from 2016 didn’t address timing, Dr. Tai said.

For the new analysis, Dr. Tai and colleagues examined six randomized studies from the United States (two), China (two), Taiwan (one), and Thailand (one) that examined the use of allopurinol (three studies), febuxostat (two studies), and probenecid (one). The studies, dated from 2012 to 2023, randomized 226 subjects with gout to early initiation of ULT vs. 219 who received placebo or delayed ULT. Subjects were tracked for a median of 28 days (15 days to 12 weeks).

Three of the studies were deemed to have high risk of bias.

There were no differences in patient-rated pain scores at various time points, duration of gout flares (examined in three studies), or recurrence of gout flares (examined in four studies).

“Other outcomes of interest, including long-term adherence, time to achieve target serum urate, and patient satisfaction with treatment, were not examined,” Dr. Tai said. “Adverse events were similar between groups.”

She cautioned that the sample sizes are small, and the findings may not be applicable to patients with tophaceous gout or comorbid renal disease.

A similar meta-analysis published in 2022 examined five studies (including three of those in the new analysis); among the five was one study from 1987 that examined azapropazone and indomethacin plus allopurinol. The review found “that initiation of ULT during an acute gout flare did not prolong the duration of acute flares.”
 

Risk for PAD

In the other study, researchers raised an alarm after finding a high rate of PAD in patients with gout regardless of whether they also had diabetes, which is a known risk factor for PAD. “Our data suggest that gout is an underrecognized risk factor for PAD and indicates the importance of assessing for PAD in gout patients,” lead author Nicole Leung, MD, of NYU Langone Health, said in a presentation.

According to Dr. Leung, there’s little known about links between PAD and gout, although she highlighted a 2018 study that found that patients with obstructive coronary artery disease were more likely to have poor outcomes if they also developed gout after catheterization. She highlighted a 2022 study that found higher rates of lower-extremity amputations in patients with gout independent of cardiovascular disease and diabetes. However, she noted that a link to PAD is unclear, and the study found a link between gout and amputations that was independent of PAD.

Patients with gout, she added, are not routinely screened for PAD.

For the new retrospective, cross-sectional analysis, Dr. Leung and colleagues examined Veterans Administration data from 2014 to 2018 for 7.2 million patients. The population was largely male.

Of those, 140,862 (2.52%) – the control group – had no gout or diabetes. In comparison, 11,449 (5.56%) of 205,904 with gout but not diabetes had PAD, for a rate 2.2 times greater than the control group). PAD occurred in 101,582 (8.70%) of 1,168,138 with diabetes but not gout, giving a rate 3.2 times greater than the control group. The rate was highest among people with both gout and diabetes, at 9.97% (9,905 of 99,377), which is about four times greater than the control group.

The link between gout and PAD remained after adjustment for creatinine levels, age, gender, and body mass index. Diabetes was linked to a higher risk for PAD than was gout, and the effect of both conditions combined was “less than additive.” This “may suggest an overlap and pathophysiology between the two,” she said.

Disclosure information was not provided. The Rheumatology Research Foundation funded the PAD study; funding information for the ULT/gout flare analysis was not provided.

WASHINGTON – The approval last year of the interleukin (IL)-36 receptor antagonist spesolimab for treating generalized pustular psoriasis flares brightened the treatment landscape for this rare condition, and a recently published phase 2 study suggests a potential role of spesolimab for flare prevention. But when it comes to pustular disease localized to the hands and feet – palmoplantar pustulosis – treatment options have only modest efficacy, and spesolimab appears not to work, according to speakers at the annual research symposium of the National Psoriasis Foundation.

“The IL-36 receptor antagonists don’t seem to be quite the answer for [palmoplantar pustulosis] that they are for generalized pustular psoriasis [GPP],” Megan H. Noe, MD, MPH, assistant professor of dermatology at Harvard Medical School and a dermatologist at Brigham and Women’s Hospital, Boston, said at the meeting.

Psoriasis affecting the hands and feet – both pustular and nonpustular – has a higher impact on quality of life and higher functional disability than does non-acral psoriasis, is less responsive to treatment, and has a “very confusing nomenclature” that complicates research and thus management, said Jason Ezra Hawkes, MD, a dermatologist in Rocklin, Calif., and former faculty member of several departments of dermatology. Both he and Dr. Noe spoke during a tough-to-treat session at the NPF meeting.

IL-17 and IL-23 blockade, as well as tumor necrosis factor (TNF) inhibition, are effective overall for palmoplantar psoriasis (nonpustular), but in general, responses are lower than for plaque psoriasis. Apremilast (Otezla), a phosphodiesterase-4 inhibitor, has some efficacy for pustular variants, but for hyperkeratotic variants it “does not perform as well as more selective inhibition of IL-17 and IL-23 blockade,” he said.

Dr. Hawkes

Palmoplantar pustulosis, and a word on generalized disease

Dermatologists are using a variety of treatments for palmoplantar pustulosis, with no clear first-line choices, Dr. Noe said. In a case series of almost 200 patients with palmoplantar pustulosis across 20 dermatology practices, published in JAMA Dermatology, 35% of patients received a systemic therapy prescription at their initial encounter – most commonly acitretin, followed by methotrexate and phototherapy. “Biologics were used, but use was varied and not as often as with oral agents,” said Dr. Noe, a coauthor of the study.

TNF blockers led to improvements ranging from 57% to 84%, depending on the agent, in a 2020 retrospective study of patients with palmoplantar pustulosis or acrodermatitis continua of Hallopeau, Dr. Noe noted. However, rates of complete clearance were only 20%-29%.

Apremilast showed modest efficacy after 5 months of treatment, with 62% of patients achieving at least a 50% improvement in the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) in a 2021 open-label, phase 2 study involving 21 patients. “This may represent a potential treatment option,” Dr. Noe said. “It’s something, but not what we’re used to seeing in our plaque psoriasis patients.”

A 2021 phase 2a, double-blind, randomized, placebo-controlled study of spesolimab in patients with palmoplantar pustulosis, meanwhile, failed to meet its primary endpoint, with only 32% of patients achieving a 50% improvement at 16 weeks, compared with 24% of patients in the placebo arm. And a recently published network meta-analysis found that none of the five drugs studied in seven randomized controlled trials – biologic or oral – was more effective than placebo for clearance or improvement of palmoplantar pustulosis.

The spesolimab (Spevigo) results have been disappointing considering the biologic’s newfound efficacy and role as the first Food and Drug Administration–approved therapy for generalized pustular disease, according to Dr. Noe. The ability of a single 900-mg intravenous dose of the IL-36 receptor antagonist to completely clear pustules at 1 week in 54% of patients with generalized disease, compared with 6% of the placebo group, was “groundbreaking,” she said, referring to results of the pivotal trial published in the New England Journal of Medicine.

And given that “preventing GPP flares is ultimately what we want,” she said, more good news was reported this year in The Lancet: The finding from an international, randomized, placebo-controlled study that high-dose subcutaneous spesolimab significantly reduced the risk of a flare over 48 weeks. “There are lots of ongoing studies right now to understand the best way to dose spesolimab,” she said.

Moreover, another IL-36 receptor antagonist, imsidolimab, is being investigated in a phase 3 trial for generalized pustular disease, she noted. A phase 2, open-label study of patients with GPP found that “more than half of patients were very much improved at 4 weeks, and some patients started showing improvement at day 3,” Dr. Noe said.

An area of research she is interested in is the potential for Janus kinase (JAK) inhibitors as a treatment for palmoplantar pustulosis. For pustulosis on the hands and feet, recent case reports describing the efficacy of JAK inhibitors have caught her eye. “Right now, all we have is this case report data, mostly with tofacitinib, but I think it’s exciting,” she said, noting a recently published report in the British Journal of Dermatology.

Palmoplantar psoriasis

Pustular psoriatic disease can be localized to the hand and/or feet only, or can co-occur with generalized pustular disease, just as palmoplantar psoriasis can be localized to the hands and/or feet or, more commonly, can co-occur with widespread plaque psoriasis. Research has shown, Dr. Hawkes said, that with both types of acral disease, many patients have or have had plaque psoriasis outside of acral sites.

The nomenclature and acronyms for palmoplantar psoriatic disease have complicated patient education, communication, and research, Dr. Hawkes said. Does PPP refer to palmoplantar psoriasis, or palmoplantar pustulosis, for instance? What is the difference between palmoplantar pustulosis (coined PPP) and palmoplantar pustular psoriasis (referred to as PPPP)?

What if disease is only on the hands, only on the feet, or only on the backs of the hands? And at what point is disease not classified as palmoplantar psoriasis, but plaque psoriasis with involvement of the hands and feet? Inconsistencies and lack of clarification lead to “confusing” literature, he said.

Heterogeneity in populations across trials resulting from “inconsistent categorization and phenotype inclusion” may partly account for the recalcitrance to treatment reported in the literature, he said. Misdiagnosis as psoriasis in cases of localized disease (confusion with eczema, for instance), and the fact that hands and feet are subject to increased trauma and injury, compared with non-acral sites, are also at play.

Trials may also allow insufficient time for improvement, compared with non-acral sites. “What we’ve learned about the hands and feet is that it takes a much longer time for disease to improve,” Dr. Hawkes said, so primary endpoints must take this into account.

There is unique immunologic signaling in palmoplantar disease that differs from the predominant signaling in traditional plaque psoriasis, he emphasized, and “mixed immunophenotypes” that need to be unraveled.

Dr. Hawkes disclosed ties with AbbVie, Arcutis, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, LEO, Lilly, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB. Dr. Noe disclosed ties to Bristol-Myers Squibb and Boehringer Ingelheim.

WASHINGTON – The approval last year of the interleukin (IL)-36 receptor antagonist spesolimab for treating generalized pustular psoriasis flares brightened the treatment landscape for this rare condition, and a recently published phase 2 study suggests a potential role of spesolimab for flare prevention. But when it comes to pustular disease localized to the hands and feet – palmoplantar pustulosis – treatment options have only modest efficacy, and spesolimab appears not to work, according to speakers at the annual research symposium of the National Psoriasis Foundation.

“The IL-36 receptor antagonists don’t seem to be quite the answer for [palmoplantar pustulosis] that they are for generalized pustular psoriasis [GPP],” Megan H. Noe, MD, MPH, assistant professor of dermatology at Harvard Medical School and a dermatologist at Brigham and Women’s Hospital, Boston, said at the meeting.

Psoriasis affecting the hands and feet – both pustular and nonpustular – has a higher impact on quality of life and higher functional disability than does non-acral psoriasis, is less responsive to treatment, and has a “very confusing nomenclature” that complicates research and thus management, said Jason Ezra Hawkes, MD, a dermatologist in Rocklin, Calif., and former faculty member of several departments of dermatology. Both he and Dr. Noe spoke during a tough-to-treat session at the NPF meeting.

IL-17 and IL-23 blockade, as well as tumor necrosis factor (TNF) inhibition, are effective overall for palmoplantar psoriasis (nonpustular), but in general, responses are lower than for plaque psoriasis. Apremilast (Otezla), a phosphodiesterase-4 inhibitor, has some efficacy for pustular variants, but for hyperkeratotic variants it “does not perform as well as more selective inhibition of IL-17 and IL-23 blockade,” he said.

Dr. Hawkes

Palmoplantar pustulosis, and a word on generalized disease

Dermatologists are using a variety of treatments for palmoplantar pustulosis, with no clear first-line choices, Dr. Noe said. In a case series of almost 200 patients with palmoplantar pustulosis across 20 dermatology practices, published in JAMA Dermatology, 35% of patients received a systemic therapy prescription at their initial encounter – most commonly acitretin, followed by methotrexate and phototherapy. “Biologics were used, but use was varied and not as often as with oral agents,” said Dr. Noe, a coauthor of the study.

TNF blockers led to improvements ranging from 57% to 84%, depending on the agent, in a 2020 retrospective study of patients with palmoplantar pustulosis or acrodermatitis continua of Hallopeau, Dr. Noe noted. However, rates of complete clearance were only 20%-29%.

Apremilast showed modest efficacy after 5 months of treatment, with 62% of patients achieving at least a 50% improvement in the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) in a 2021 open-label, phase 2 study involving 21 patients. “This may represent a potential treatment option,” Dr. Noe said. “It’s something, but not what we’re used to seeing in our plaque psoriasis patients.”

A 2021 phase 2a, double-blind, randomized, placebo-controlled study of spesolimab in patients with palmoplantar pustulosis, meanwhile, failed to meet its primary endpoint, with only 32% of patients achieving a 50% improvement at 16 weeks, compared with 24% of patients in the placebo arm. And a recently published network meta-analysis found that none of the five drugs studied in seven randomized controlled trials – biologic or oral – was more effective than placebo for clearance or improvement of palmoplantar pustulosis.

The spesolimab (Spevigo) results have been disappointing considering the biologic’s newfound efficacy and role as the first Food and Drug Administration–approved therapy for generalized pustular disease, according to Dr. Noe. The ability of a single 900-mg intravenous dose of the IL-36 receptor antagonist to completely clear pustules at 1 week in 54% of patients with generalized disease, compared with 6% of the placebo group, was “groundbreaking,” she said, referring to results of the pivotal trial published in the New England Journal of Medicine.

And given that “preventing GPP flares is ultimately what we want,” she said, more good news was reported this year in The Lancet: The finding from an international, randomized, placebo-controlled study that high-dose subcutaneous spesolimab significantly reduced the risk of a flare over 48 weeks. “There are lots of ongoing studies right now to understand the best way to dose spesolimab,” she said.

Moreover, another IL-36 receptor antagonist, imsidolimab, is being investigated in a phase 3 trial for generalized pustular disease, she noted. A phase 2, open-label study of patients with GPP found that “more than half of patients were very much improved at 4 weeks, and some patients started showing improvement at day 3,” Dr. Noe said.

An area of research she is interested in is the potential for Janus kinase (JAK) inhibitors as a treatment for palmoplantar pustulosis. For pustulosis on the hands and feet, recent case reports describing the efficacy of JAK inhibitors have caught her eye. “Right now, all we have is this case report data, mostly with tofacitinib, but I think it’s exciting,” she said, noting a recently published report in the British Journal of Dermatology.

Palmoplantar psoriasis

Pustular psoriatic disease can be localized to the hand and/or feet only, or can co-occur with generalized pustular disease, just as palmoplantar psoriasis can be localized to the hands and/or feet or, more commonly, can co-occur with widespread plaque psoriasis. Research has shown, Dr. Hawkes said, that with both types of acral disease, many patients have or have had plaque psoriasis outside of acral sites.

The nomenclature and acronyms for palmoplantar psoriatic disease have complicated patient education, communication, and research, Dr. Hawkes said. Does PPP refer to palmoplantar psoriasis, or palmoplantar pustulosis, for instance? What is the difference between palmoplantar pustulosis (coined PPP) and palmoplantar pustular psoriasis (referred to as PPPP)?

What if disease is only on the hands, only on the feet, or only on the backs of the hands? And at what point is disease not classified as palmoplantar psoriasis, but plaque psoriasis with involvement of the hands and feet? Inconsistencies and lack of clarification lead to “confusing” literature, he said.

Heterogeneity in populations across trials resulting from “inconsistent categorization and phenotype inclusion” may partly account for the recalcitrance to treatment reported in the literature, he said. Misdiagnosis as psoriasis in cases of localized disease (confusion with eczema, for instance), and the fact that hands and feet are subject to increased trauma and injury, compared with non-acral sites, are also at play.

Trials may also allow insufficient time for improvement, compared with non-acral sites. “What we’ve learned about the hands and feet is that it takes a much longer time for disease to improve,” Dr. Hawkes said, so primary endpoints must take this into account.

There is unique immunologic signaling in palmoplantar disease that differs from the predominant signaling in traditional plaque psoriasis, he emphasized, and “mixed immunophenotypes” that need to be unraveled.

Dr. Hawkes disclosed ties with AbbVie, Arcutis, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, LEO, Lilly, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB. Dr. Noe disclosed ties to Bristol-Myers Squibb and Boehringer Ingelheim.

WASHINGTON – The approval last year of the interleukin (IL)-36 receptor antagonist spesolimab for treating generalized pustular psoriasis flares brightened the treatment landscape for this rare condition, and a recently published phase 2 study suggests a potential role of spesolimab for flare prevention. But when it comes to pustular disease localized to the hands and feet – palmoplantar pustulosis – treatment options have only modest efficacy, and spesolimab appears not to work, according to speakers at the annual research symposium of the National Psoriasis Foundation.

“The IL-36 receptor antagonists don’t seem to be quite the answer for [palmoplantar pustulosis] that they are for generalized pustular psoriasis [GPP],” Megan H. Noe, MD, MPH, assistant professor of dermatology at Harvard Medical School and a dermatologist at Brigham and Women’s Hospital, Boston, said at the meeting.

Psoriasis affecting the hands and feet – both pustular and nonpustular – has a higher impact on quality of life and higher functional disability than does non-acral psoriasis, is less responsive to treatment, and has a “very confusing nomenclature” that complicates research and thus management, said Jason Ezra Hawkes, MD, a dermatologist in Rocklin, Calif., and former faculty member of several departments of dermatology. Both he and Dr. Noe spoke during a tough-to-treat session at the NPF meeting.

IL-17 and IL-23 blockade, as well as tumor necrosis factor (TNF) inhibition, are effective overall for palmoplantar psoriasis (nonpustular), but in general, responses are lower than for plaque psoriasis. Apremilast (Otezla), a phosphodiesterase-4 inhibitor, has some efficacy for pustular variants, but for hyperkeratotic variants it “does not perform as well as more selective inhibition of IL-17 and IL-23 blockade,” he said.

Dr. Hawkes

Palmoplantar pustulosis, and a word on generalized disease

Dermatologists are using a variety of treatments for palmoplantar pustulosis, with no clear first-line choices, Dr. Noe said. In a case series of almost 200 patients with palmoplantar pustulosis across 20 dermatology practices, published in JAMA Dermatology, 35% of patients received a systemic therapy prescription at their initial encounter – most commonly acitretin, followed by methotrexate and phototherapy. “Biologics were used, but use was varied and not as often as with oral agents,” said Dr. Noe, a coauthor of the study.

TNF blockers led to improvements ranging from 57% to 84%, depending on the agent, in a 2020 retrospective study of patients with palmoplantar pustulosis or acrodermatitis continua of Hallopeau, Dr. Noe noted. However, rates of complete clearance were only 20%-29%.

Apremilast showed modest efficacy after 5 months of treatment, with 62% of patients achieving at least a 50% improvement in the Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) in a 2021 open-label, phase 2 study involving 21 patients. “This may represent a potential treatment option,” Dr. Noe said. “It’s something, but not what we’re used to seeing in our plaque psoriasis patients.”

A 2021 phase 2a, double-blind, randomized, placebo-controlled study of spesolimab in patients with palmoplantar pustulosis, meanwhile, failed to meet its primary endpoint, with only 32% of patients achieving a 50% improvement at 16 weeks, compared with 24% of patients in the placebo arm. And a recently published network meta-analysis found that none of the five drugs studied in seven randomized controlled trials – biologic or oral – was more effective than placebo for clearance or improvement of palmoplantar pustulosis.

The spesolimab (Spevigo) results have been disappointing considering the biologic’s newfound efficacy and role as the first Food and Drug Administration–approved therapy for generalized pustular disease, according to Dr. Noe. The ability of a single 900-mg intravenous dose of the IL-36 receptor antagonist to completely clear pustules at 1 week in 54% of patients with generalized disease, compared with 6% of the placebo group, was “groundbreaking,” she said, referring to results of the pivotal trial published in the New England Journal of Medicine.

And given that “preventing GPP flares is ultimately what we want,” she said, more good news was reported this year in The Lancet: The finding from an international, randomized, placebo-controlled study that high-dose subcutaneous spesolimab significantly reduced the risk of a flare over 48 weeks. “There are lots of ongoing studies right now to understand the best way to dose spesolimab,” she said.

Moreover, another IL-36 receptor antagonist, imsidolimab, is being investigated in a phase 3 trial for generalized pustular disease, she noted. A phase 2, open-label study of patients with GPP found that “more than half of patients were very much improved at 4 weeks, and some patients started showing improvement at day 3,” Dr. Noe said.

An area of research she is interested in is the potential for Janus kinase (JAK) inhibitors as a treatment for palmoplantar pustulosis. For pustulosis on the hands and feet, recent case reports describing the efficacy of JAK inhibitors have caught her eye. “Right now, all we have is this case report data, mostly with tofacitinib, but I think it’s exciting,” she said, noting a recently published report in the British Journal of Dermatology.

Palmoplantar psoriasis

Pustular psoriatic disease can be localized to the hand and/or feet only, or can co-occur with generalized pustular disease, just as palmoplantar psoriasis can be localized to the hands and/or feet or, more commonly, can co-occur with widespread plaque psoriasis. Research has shown, Dr. Hawkes said, that with both types of acral disease, many patients have or have had plaque psoriasis outside of acral sites.

The nomenclature and acronyms for palmoplantar psoriatic disease have complicated patient education, communication, and research, Dr. Hawkes said. Does PPP refer to palmoplantar psoriasis, or palmoplantar pustulosis, for instance? What is the difference between palmoplantar pustulosis (coined PPP) and palmoplantar pustular psoriasis (referred to as PPPP)?

What if disease is only on the hands, only on the feet, or only on the backs of the hands? And at what point is disease not classified as palmoplantar psoriasis, but plaque psoriasis with involvement of the hands and feet? Inconsistencies and lack of clarification lead to “confusing” literature, he said.

Heterogeneity in populations across trials resulting from “inconsistent categorization and phenotype inclusion” may partly account for the recalcitrance to treatment reported in the literature, he said. Misdiagnosis as psoriasis in cases of localized disease (confusion with eczema, for instance), and the fact that hands and feet are subject to increased trauma and injury, compared with non-acral sites, are also at play.

Trials may also allow insufficient time for improvement, compared with non-acral sites. “What we’ve learned about the hands and feet is that it takes a much longer time for disease to improve,” Dr. Hawkes said, so primary endpoints must take this into account.

There is unique immunologic signaling in palmoplantar disease that differs from the predominant signaling in traditional plaque psoriasis, he emphasized, and “mixed immunophenotypes” that need to be unraveled.

Dr. Hawkes disclosed ties with AbbVie, Arcutis, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, LEO, Lilly, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB. Dr. Noe disclosed ties to Bristol-Myers Squibb and Boehringer Ingelheim.

TOPLINE:

Use of Janus kinase (JAK) inhibitors is associated with a nearly fourfold increase in risk of acne compared with placebo, according to an analysis of 25 JAK inhibitor studies.

METHODOLOGY:

• Acne has been reported to be an adverse effect of JAK inhibitors, but not much is known about how common acne is overall and how incidence differs between different JAK inhibitors and the disease being treated.
• For the systematic review and meta-analysis, researchers identified 25 phase 2 or 3 randomized, controlled trials that reported acne as an adverse event associated with the use of JAK inhibitors.
• The study population included 10,839 participants (54% male, 46% female).
• The primary outcome was the incidence of acne following a period of JAK inhibitor use.

TAKEAWAY:

• Overall, the risk of acne was significantly higher among those treated with JAK inhibitors in comparison with patients given placebo in a pooled analysis (odds ratio [OR], 3.83).
• The risk of acne was highest with abrocitinib (OR, 13.47), followed by baricitinib (OR, 4.96), upadacitinib (OR, 4.79), deuruxolitinib (OR, 3.30), and deucravacitinib (OR, 2.64). By JAK inhibitor class, results were as follows: JAK1-specific inhibitors (OR, 4.69), combined JAK1 and JAK2 inhibitors (OR, 3.43), and tyrosine kinase 2 inhibitors (OR, 2.64).
• In a subgroup analysis, risk of acne was higher among patients using JAK inhibitors for dermatologic conditions in comparison with those using JAK inhibitors for nondermatologic conditions (OR, 4.67 vs 1.18).
• Age and gender had no apparent impact on the effect of JAK inhibitor use on acne risk.

IN PRACTICE:

“The occurrence of acne following treatment with certain classes of JAK inhibitors is of potential concern, as this adverse effect may jeopardize treatment adherence among some patients,” the researchers wrote. More studies are needed “to characterize the underlying mechanism of acne with JAK inhibitor use and to identify best practices for treatment,” they added.

SOURCE:

The lead author was Jeremy Martinez, MPH, of Harvard Medical School, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The review was limited by the variable classification and reporting of acne across studies, the potential exclusion of relevant studies, and the small number of studies for certain drugs.

DISCLOSURES:

The studies were mainly funded by the pharmaceutical industry. Mr. Martinez disclosed no relevant financial relationships. Several coauthors have ties with Dexcel Pharma Technologies, AbbVie, Concert, Pfizer, 3Derm Systems, Incyte, Aclaris, Eli Lilly, Concert, Equillium, ASLAN, ACOM, and Boehringer Ingelheim.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Use of Janus kinase (JAK) inhibitors is associated with a nearly fourfold increase in risk of acne compared with placebo, according to an analysis of 25 JAK inhibitor studies.

METHODOLOGY:

• Acne has been reported to be an adverse effect of JAK inhibitors, but not much is known about how common acne is overall and how incidence differs between different JAK inhibitors and the disease being treated.
• For the systematic review and meta-analysis, researchers identified 25 phase 2 or 3 randomized, controlled trials that reported acne as an adverse event associated with the use of JAK inhibitors.
• The study population included 10,839 participants (54% male, 46% female).
• The primary outcome was the incidence of acne following a period of JAK inhibitor use.

TAKEAWAY:

• Overall, the risk of acne was significantly higher among those treated with JAK inhibitors in comparison with patients given placebo in a pooled analysis (odds ratio [OR], 3.83).
• The risk of acne was highest with abrocitinib (OR, 13.47), followed by baricitinib (OR, 4.96), upadacitinib (OR, 4.79), deuruxolitinib (OR, 3.30), and deucravacitinib (OR, 2.64). By JAK inhibitor class, results were as follows: JAK1-specific inhibitors (OR, 4.69), combined JAK1 and JAK2 inhibitors (OR, 3.43), and tyrosine kinase 2 inhibitors (OR, 2.64).
• In a subgroup analysis, risk of acne was higher among patients using JAK inhibitors for dermatologic conditions in comparison with those using JAK inhibitors for nondermatologic conditions (OR, 4.67 vs 1.18).
• Age and gender had no apparent impact on the effect of JAK inhibitor use on acne risk.

IN PRACTICE:

“The occurrence of acne following treatment with certain classes of JAK inhibitors is of potential concern, as this adverse effect may jeopardize treatment adherence among some patients,” the researchers wrote. More studies are needed “to characterize the underlying mechanism of acne with JAK inhibitor use and to identify best practices for treatment,” they added.

SOURCE:

The lead author was Jeremy Martinez, MPH, of Harvard Medical School, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The review was limited by the variable classification and reporting of acne across studies, the potential exclusion of relevant studies, and the small number of studies for certain drugs.

DISCLOSURES:

The studies were mainly funded by the pharmaceutical industry. Mr. Martinez disclosed no relevant financial relationships. Several coauthors have ties with Dexcel Pharma Technologies, AbbVie, Concert, Pfizer, 3Derm Systems, Incyte, Aclaris, Eli Lilly, Concert, Equillium, ASLAN, ACOM, and Boehringer Ingelheim.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Use of Janus kinase (JAK) inhibitors is associated with a nearly fourfold increase in risk of acne compared with placebo, according to an analysis of 25 JAK inhibitor studies.

METHODOLOGY:

• Acne has been reported to be an adverse effect of JAK inhibitors, but not much is known about how common acne is overall and how incidence differs between different JAK inhibitors and the disease being treated.
• For the systematic review and meta-analysis, researchers identified 25 phase 2 or 3 randomized, controlled trials that reported acne as an adverse event associated with the use of JAK inhibitors.
• The study population included 10,839 participants (54% male, 46% female).
• The primary outcome was the incidence of acne following a period of JAK inhibitor use.

TAKEAWAY:

• Overall, the risk of acne was significantly higher among those treated with JAK inhibitors in comparison with patients given placebo in a pooled analysis (odds ratio [OR], 3.83).
• The risk of acne was highest with abrocitinib (OR, 13.47), followed by baricitinib (OR, 4.96), upadacitinib (OR, 4.79), deuruxolitinib (OR, 3.30), and deucravacitinib (OR, 2.64). By JAK inhibitor class, results were as follows: JAK1-specific inhibitors (OR, 4.69), combined JAK1 and JAK2 inhibitors (OR, 3.43), and tyrosine kinase 2 inhibitors (OR, 2.64).
• In a subgroup analysis, risk of acne was higher among patients using JAK inhibitors for dermatologic conditions in comparison with those using JAK inhibitors for nondermatologic conditions (OR, 4.67 vs 1.18).
• Age and gender had no apparent impact on the effect of JAK inhibitor use on acne risk.

IN PRACTICE:

“The occurrence of acne following treatment with certain classes of JAK inhibitors is of potential concern, as this adverse effect may jeopardize treatment adherence among some patients,” the researchers wrote. More studies are needed “to characterize the underlying mechanism of acne with JAK inhibitor use and to identify best practices for treatment,” they added.

SOURCE:

The lead author was Jeremy Martinez, MPH, of Harvard Medical School, Boston. The study was published online in JAMA Dermatology.

LIMITATIONS:

The review was limited by the variable classification and reporting of acne across studies, the potential exclusion of relevant studies, and the small number of studies for certain drugs.

DISCLOSURES:

The studies were mainly funded by the pharmaceutical industry. Mr. Martinez disclosed no relevant financial relationships. Several coauthors have ties with Dexcel Pharma Technologies, AbbVie, Concert, Pfizer, 3Derm Systems, Incyte, Aclaris, Eli Lilly, Concert, Equillium, ASLAN, ACOM, and Boehringer Ingelheim.
 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Today we are going to talk about the American Geriatrics Society 2023 updated Beers Criteria guidance for medication use in older adults. These criteria have been updated and revised approximately every 5 years since 1991 and serve to alert us to medications for which the risk-benefit ratio is not as good in older adults as in the rest of the population.

These are important criteria because medications are metabolized differently in older adults and have different effects compared with younger patients. For the sake of these criteria, older adults are 65 years of age or older. That said, we know that everyone from 65 to 100 is not the same. As people age, they develop more comorbidities, they become more frail, and they are more sensitive to the effects and side effects of drugs.

The guidance covers potentially inappropriate medications for older adults. The word “potentially” is important because this is guidance. As clinicians, we make decisions involving individuals. This guidance should be used with judgment, integrating the clinical context of the individual patient.

There is a lot in this guidance. I am going to try to cover what I feel are the most important points.

Aspirin. Since the risk for major bleeding increases with age, for primary prevention of atherosclerotic cardiovascular disease, the harm can be greater than the benefit in older adults, so aspirin should not be used for primary prevention. Aspirin remains indicated for secondary prevention in individuals with established cardiovascular disease.

Warfarin. For treatment of atrial fibrillation or venous thromboembolism (deep vein thrombosis or pulmonary embolism), warfarin should be avoided if possible. Warfarin has a higher risk for major bleeding, particularly intracranial bleeding, than direct oral anticoagulants (DOACs); therefore the latter are preferred. Rivaroxaban should be avoided, as it has a higher risk for major bleeding in older adults than the other DOACs. Apixaban is preferred over dabigatran. If a patient is well controlled on warfarin, you can consider continuing that treatment.

Antipsychotics. These include first- and second-generation antipsychotics such as aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and others. The guidance says to avoid these agents except for FDA-approved indications such as schizophrenia, bipolar disorder, and adjuvant treatment of depression. Use of these antipsychotics can increase risk for stroke, heart attack, and mortality. Essentially, the guidance says do not use these medications lightly for the treatment of agitated dementia. For those of us with older patients, this can get tricky because agitated dementia is a difficult issue for which there are no good effective medications. The Beers guidance recognizes this in saying that these medications should be avoided unless behavioral interventions have failed. So, there are times where you may need to use these medicines, but use them judiciously.

For patients with dementia, anticholinergics, antipsychotics, and benzodiazepines should be avoided if possible.

Benzodiazepines. Benzodiazepines should also be avoided because older adults have increased sensitivity to their effects due to slower metabolism and clearance of these medications, which can lead to a much longer half-life and higher serum level. In older adults, benzodiazepines increase the risk for cognitive impairment, delirium, falls, fractures, and even motor accidents. The same concerns affect the group of non-benzodiazepine sleeping medicines known as “Z-drugs.”

Nonsteroidal anti-inflammatory drugs (NSAIDs). Used frequently in our practices, NSAIDs are nevertheless on the list. As we think through the risk-benefit ratio of using NSAIDs in older adults, we often underappreciate the risks of these agents. Upper gastrointestinal ulcers with bleeding occur in approximately 1% of patients treated for 3-6 months with an NSAID and in 2%-4% of patients treated for a year. NSAIDs also increase the risk for renal impairment and cardiovascular disease.

Other medications to avoid (if possible). These include:

Sulfonylureas, due to a high risk for hypoglycemia. A short-acting sulfonylurea, such as glipizide, should be used if one is needed.

Proton pump inhibitors should not be used long-term if it can be avoided.

Digoxin should not be first-line treatment for atrial fibrillation or heart failure. Decreased renal clearance in older adults can lead to toxic levels of digoxin, particularly during acute illnesses. Avoid doses > 0.125 mg/day.

Nitrofurantoin should be avoided when the patient’s creatinine clearance is < 30 or for long-term suppressive therapy.

Avoid combining medications that have high anticholinergic side effects, such as scopolamine, diphenhydramine, oxybutynin, cyclobenzaprine, and others.

It is always important to understand the benefits and the risks of the drugs we prescribe. It is also important to remember that older adults are a particularly vulnerable population. The Beers criteria provide important guidance, which we can then use to make decisions about medicines for individual patients.

Dr. Skolnik is a professor in the department of family medicine at Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director in the department of family medicine at Abington (Pa.) Jefferson Health. He disclosed ties with AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GSK, Merck, Sanofi, Sanofi Pasteur, and Teva.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Today we are going to talk about the American Geriatrics Society 2023 updated Beers Criteria guidance for medication use in older adults. These criteria have been updated and revised approximately every 5 years since 1991 and serve to alert us to medications for which the risk-benefit ratio is not as good in older adults as in the rest of the population.

These are important criteria because medications are metabolized differently in older adults and have different effects compared with younger patients. For the sake of these criteria, older adults are 65 years of age or older. That said, we know that everyone from 65 to 100 is not the same. As people age, they develop more comorbidities, they become more frail, and they are more sensitive to the effects and side effects of drugs.

The guidance covers potentially inappropriate medications for older adults. The word “potentially” is important because this is guidance. As clinicians, we make decisions involving individuals. This guidance should be used with judgment, integrating the clinical context of the individual patient.

There is a lot in this guidance. I am going to try to cover what I feel are the most important points.

Aspirin. Since the risk for major bleeding increases with age, for primary prevention of atherosclerotic cardiovascular disease, the harm can be greater than the benefit in older adults, so aspirin should not be used for primary prevention. Aspirin remains indicated for secondary prevention in individuals with established cardiovascular disease.

Warfarin. For treatment of atrial fibrillation or venous thromboembolism (deep vein thrombosis or pulmonary embolism), warfarin should be avoided if possible. Warfarin has a higher risk for major bleeding, particularly intracranial bleeding, than direct oral anticoagulants (DOACs); therefore the latter are preferred. Rivaroxaban should be avoided, as it has a higher risk for major bleeding in older adults than the other DOACs. Apixaban is preferred over dabigatran. If a patient is well controlled on warfarin, you can consider continuing that treatment.

Antipsychotics. These include first- and second-generation antipsychotics such as aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and others. The guidance says to avoid these agents except for FDA-approved indications such as schizophrenia, bipolar disorder, and adjuvant treatment of depression. Use of these antipsychotics can increase risk for stroke, heart attack, and mortality. Essentially, the guidance says do not use these medications lightly for the treatment of agitated dementia. For those of us with older patients, this can get tricky because agitated dementia is a difficult issue for which there are no good effective medications. The Beers guidance recognizes this in saying that these medications should be avoided unless behavioral interventions have failed. So, there are times where you may need to use these medicines, but use them judiciously.

For patients with dementia, anticholinergics, antipsychotics, and benzodiazepines should be avoided if possible.

Benzodiazepines. Benzodiazepines should also be avoided because older adults have increased sensitivity to their effects due to slower metabolism and clearance of these medications, which can lead to a much longer half-life and higher serum level. In older adults, benzodiazepines increase the risk for cognitive impairment, delirium, falls, fractures, and even motor accidents. The same concerns affect the group of non-benzodiazepine sleeping medicines known as “Z-drugs.”

Nonsteroidal anti-inflammatory drugs (NSAIDs). Used frequently in our practices, NSAIDs are nevertheless on the list. As we think through the risk-benefit ratio of using NSAIDs in older adults, we often underappreciate the risks of these agents. Upper gastrointestinal ulcers with bleeding occur in approximately 1% of patients treated for 3-6 months with an NSAID and in 2%-4% of patients treated for a year. NSAIDs also increase the risk for renal impairment and cardiovascular disease.

Other medications to avoid (if possible). These include:

Sulfonylureas, due to a high risk for hypoglycemia. A short-acting sulfonylurea, such as glipizide, should be used if one is needed.

Proton pump inhibitors should not be used long-term if it can be avoided.

Digoxin should not be first-line treatment for atrial fibrillation or heart failure. Decreased renal clearance in older adults can lead to toxic levels of digoxin, particularly during acute illnesses. Avoid doses > 0.125 mg/day.

Nitrofurantoin should be avoided when the patient’s creatinine clearance is < 30 or for long-term suppressive therapy.

Avoid combining medications that have high anticholinergic side effects, such as scopolamine, diphenhydramine, oxybutynin, cyclobenzaprine, and others.

It is always important to understand the benefits and the risks of the drugs we prescribe. It is also important to remember that older adults are a particularly vulnerable population. The Beers criteria provide important guidance, which we can then use to make decisions about medicines for individual patients.

Dr. Skolnik is a professor in the department of family medicine at Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director in the department of family medicine at Abington (Pa.) Jefferson Health. He disclosed ties with AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GSK, Merck, Sanofi, Sanofi Pasteur, and Teva.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Today we are going to talk about the American Geriatrics Society 2023 updated Beers Criteria guidance for medication use in older adults. These criteria have been updated and revised approximately every 5 years since 1991 and serve to alert us to medications for which the risk-benefit ratio is not as good in older adults as in the rest of the population.

These are important criteria because medications are metabolized differently in older adults and have different effects compared with younger patients. For the sake of these criteria, older adults are 65 years of age or older. That said, we know that everyone from 65 to 100 is not the same. As people age, they develop more comorbidities, they become more frail, and they are more sensitive to the effects and side effects of drugs.

The guidance covers potentially inappropriate medications for older adults. The word “potentially” is important because this is guidance. As clinicians, we make decisions involving individuals. This guidance should be used with judgment, integrating the clinical context of the individual patient.

There is a lot in this guidance. I am going to try to cover what I feel are the most important points.

Aspirin. Since the risk for major bleeding increases with age, for primary prevention of atherosclerotic cardiovascular disease, the harm can be greater than the benefit in older adults, so aspirin should not be used for primary prevention. Aspirin remains indicated for secondary prevention in individuals with established cardiovascular disease.

Warfarin. For treatment of atrial fibrillation or venous thromboembolism (deep vein thrombosis or pulmonary embolism), warfarin should be avoided if possible. Warfarin has a higher risk for major bleeding, particularly intracranial bleeding, than direct oral anticoagulants (DOACs); therefore the latter are preferred. Rivaroxaban should be avoided, as it has a higher risk for major bleeding in older adults than the other DOACs. Apixaban is preferred over dabigatran. If a patient is well controlled on warfarin, you can consider continuing that treatment.

Antipsychotics. These include first- and second-generation antipsychotics such as aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and others. The guidance says to avoid these agents except for FDA-approved indications such as schizophrenia, bipolar disorder, and adjuvant treatment of depression. Use of these antipsychotics can increase risk for stroke, heart attack, and mortality. Essentially, the guidance says do not use these medications lightly for the treatment of agitated dementia. For those of us with older patients, this can get tricky because agitated dementia is a difficult issue for which there are no good effective medications. The Beers guidance recognizes this in saying that these medications should be avoided unless behavioral interventions have failed. So, there are times where you may need to use these medicines, but use them judiciously.

For patients with dementia, anticholinergics, antipsychotics, and benzodiazepines should be avoided if possible.

Benzodiazepines. Benzodiazepines should also be avoided because older adults have increased sensitivity to their effects due to slower metabolism and clearance of these medications, which can lead to a much longer half-life and higher serum level. In older adults, benzodiazepines increase the risk for cognitive impairment, delirium, falls, fractures, and even motor accidents. The same concerns affect the group of non-benzodiazepine sleeping medicines known as “Z-drugs.”

Nonsteroidal anti-inflammatory drugs (NSAIDs). Used frequently in our practices, NSAIDs are nevertheless on the list. As we think through the risk-benefit ratio of using NSAIDs in older adults, we often underappreciate the risks of these agents. Upper gastrointestinal ulcers with bleeding occur in approximately 1% of patients treated for 3-6 months with an NSAID and in 2%-4% of patients treated for a year. NSAIDs also increase the risk for renal impairment and cardiovascular disease.

Other medications to avoid (if possible). These include:

Sulfonylureas, due to a high risk for hypoglycemia. A short-acting sulfonylurea, such as glipizide, should be used if one is needed.

Proton pump inhibitors should not be used long-term if it can be avoided.

Digoxin should not be first-line treatment for atrial fibrillation or heart failure. Decreased renal clearance in older adults can lead to toxic levels of digoxin, particularly during acute illnesses. Avoid doses > 0.125 mg/day.

Nitrofurantoin should be avoided when the patient’s creatinine clearance is < 30 or for long-term suppressive therapy.

Avoid combining medications that have high anticholinergic side effects, such as scopolamine, diphenhydramine, oxybutynin, cyclobenzaprine, and others.

It is always important to understand the benefits and the risks of the drugs we prescribe. It is also important to remember that older adults are a particularly vulnerable population. The Beers criteria provide important guidance, which we can then use to make decisions about medicines for individual patients.

Dr. Skolnik is a professor in the department of family medicine at Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director in the department of family medicine at Abington (Pa.) Jefferson Health. He disclosed ties with AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GSK, Merck, Sanofi, Sanofi Pasteur, and Teva.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I am far from the only doctor, and certainly far from the only oncologist, to recently comment on the topic of Maintenance of Certification. Of course, this is happening in a wider debate about our relationship as subspecialists to the American Board of Internal Medicine, and what they deem acceptable for the recertification of doctors in practice.

My take is that every oncologist is already engaged in lifelong learning. One of the things I tell my patients is that if I practiced exactly the way I was trained to practice — and I had a very good fellowship program with superb faculty – if I practiced the way they taught me, it would now be malpractice. I finished my fellowship in 2012, just over a decade ago. The rate of progress in the interim is simply staggering. It looks so different now than it did then.

For instance, 2011 was my first experience ever using a form of immunotherapy. It was an anti-CTLA4 agent, ipilimumab, and I was treating metastatic melanoma. I learned in that instance just how effective these drugs can be, but also how toxic they can be. Ever since then, I’ve been refining my use of immunotherapy. We do that iteratively. We do that as we encounter patients and as we try to meet their needs.

I do understand that the ABIM is saying they want an independent governing body to legislate that process. I think the reason this is stuck in the craw of so many oncologists is that we demonstrate our commitment to continuing medical education all the time.

I’m recording this in my office, which is separate from the space where I see patients. I see patients in a different group of exam rooms for their privacy and it’s a better setup for aspects of the physical encounter. Not a single patient has ever asked to come into my office and see my diplomas, and I sometimes wonder if I keep them here mostly as a visual cue to myself, sort of an antidote to ward off imposter syndrome and remind myself, Oh yeah – I earned these. I earned these through formal training.

Then something happens once you finish your training, whether it’s residency or fellowship, and you become an attending. I think you feel a weight of responsibility, the responsibility of independent learning. All of us are doing this. We have to do this. The field is moving along at such a rapid clip that it’s essentially built into what we do that we are going to keep up. In fact, channels such as the various aspects of social media are a way I curate my own information feed so I can stay up to speed and not feel like I’m drowning in a deluge of new data.

But what’s hard to demonstrate to the ABIM is that [this learning] is already happening. I think we can do it if we submit our records of CME credits that we formally accrue. The reason this is such an almost insult to oncologists in practice is because it is a necessary part of our day-to-day existence to keep apprised of developments so we can apply them to patient care.

One litmus test of attending a medical conference like the annual meeting of the American Society of Clinical Oncology is to ask oneself, When I go back to clinic, is this meeting going to change the way that I take care of patients? The answer almost invariably these days is yes. I go to multiple meetings per year, and I think it’s the exception, not the rule, that I return home and nothing changes in my management patterns. Again, this process is happening whether the ABIM recognizes it or not.

Lastly, I sat down in the fall of 2022 and I did my recertification. I looked at the span of all the things that had happened between 2012, when I first sat for my board examination in medical oncology, and 2022. It was staggering. I think the reason that it wasn’t such an overwhelming amount of information to review is that I had actually been accreting it slowly and gradually, month by month, year by year throughout that decade.

Again, it’s necessary that the ABIM hear us, hear oncologists, and know that of all the medical subspecialties they govern, it is basically already an essential task of our day-to-day professional existence that we engage in lifelong learning. To suggest otherwise really paints us as outdated. The reason that matters so much is that if we’re not up-to-date, then we are underserving our patients.

Mark A. Lewis, MD, is director of gastrointestinal oncology at Intermountain Healthcare in Salt Lake City. He reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I am far from the only doctor, and certainly far from the only oncologist, to recently comment on the topic of Maintenance of Certification. Of course, this is happening in a wider debate about our relationship as subspecialists to the American Board of Internal Medicine, and what they deem acceptable for the recertification of doctors in practice.

My take is that every oncologist is already engaged in lifelong learning. One of the things I tell my patients is that if I practiced exactly the way I was trained to practice — and I had a very good fellowship program with superb faculty – if I practiced the way they taught me, it would now be malpractice. I finished my fellowship in 2012, just over a decade ago. The rate of progress in the interim is simply staggering. It looks so different now than it did then.

For instance, 2011 was my first experience ever using a form of immunotherapy. It was an anti-CTLA4 agent, ipilimumab, and I was treating metastatic melanoma. I learned in that instance just how effective these drugs can be, but also how toxic they can be. Ever since then, I’ve been refining my use of immunotherapy. We do that iteratively. We do that as we encounter patients and as we try to meet their needs.

I do understand that the ABIM is saying they want an independent governing body to legislate that process. I think the reason this is stuck in the craw of so many oncologists is that we demonstrate our commitment to continuing medical education all the time.

I’m recording this in my office, which is separate from the space where I see patients. I see patients in a different group of exam rooms for their privacy and it’s a better setup for aspects of the physical encounter. Not a single patient has ever asked to come into my office and see my diplomas, and I sometimes wonder if I keep them here mostly as a visual cue to myself, sort of an antidote to ward off imposter syndrome and remind myself, Oh yeah – I earned these. I earned these through formal training.

Then something happens once you finish your training, whether it’s residency or fellowship, and you become an attending. I think you feel a weight of responsibility, the responsibility of independent learning. All of us are doing this. We have to do this. The field is moving along at such a rapid clip that it’s essentially built into what we do that we are going to keep up. In fact, channels such as the various aspects of social media are a way I curate my own information feed so I can stay up to speed and not feel like I’m drowning in a deluge of new data.

But what’s hard to demonstrate to the ABIM is that [this learning] is already happening. I think we can do it if we submit our records of CME credits that we formally accrue. The reason this is such an almost insult to oncologists in practice is because it is a necessary part of our day-to-day existence to keep apprised of developments so we can apply them to patient care.

One litmus test of attending a medical conference like the annual meeting of the American Society of Clinical Oncology is to ask oneself, When I go back to clinic, is this meeting going to change the way that I take care of patients? The answer almost invariably these days is yes. I go to multiple meetings per year, and I think it’s the exception, not the rule, that I return home and nothing changes in my management patterns. Again, this process is happening whether the ABIM recognizes it or not.

Lastly, I sat down in the fall of 2022 and I did my recertification. I looked at the span of all the things that had happened between 2012, when I first sat for my board examination in medical oncology, and 2022. It was staggering. I think the reason that it wasn’t such an overwhelming amount of information to review is that I had actually been accreting it slowly and gradually, month by month, year by year throughout that decade.

Again, it’s necessary that the ABIM hear us, hear oncologists, and know that of all the medical subspecialties they govern, it is basically already an essential task of our day-to-day professional existence that we engage in lifelong learning. To suggest otherwise really paints us as outdated. The reason that matters so much is that if we’re not up-to-date, then we are underserving our patients.

Mark A. Lewis, MD, is director of gastrointestinal oncology at Intermountain Healthcare in Salt Lake City. He reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I am far from the only doctor, and certainly far from the only oncologist, to recently comment on the topic of Maintenance of Certification. Of course, this is happening in a wider debate about our relationship as subspecialists to the American Board of Internal Medicine, and what they deem acceptable for the recertification of doctors in practice.

My take is that every oncologist is already engaged in lifelong learning. One of the things I tell my patients is that if I practiced exactly the way I was trained to practice — and I had a very good fellowship program with superb faculty – if I practiced the way they taught me, it would now be malpractice. I finished my fellowship in 2012, just over a decade ago. The rate of progress in the interim is simply staggering. It looks so different now than it did then.

For instance, 2011 was my first experience ever using a form of immunotherapy. It was an anti-CTLA4 agent, ipilimumab, and I was treating metastatic melanoma. I learned in that instance just how effective these drugs can be, but also how toxic they can be. Ever since then, I’ve been refining my use of immunotherapy. We do that iteratively. We do that as we encounter patients and as we try to meet their needs.

I do understand that the ABIM is saying they want an independent governing body to legislate that process. I think the reason this is stuck in the craw of so many oncologists is that we demonstrate our commitment to continuing medical education all the time.

I’m recording this in my office, which is separate from the space where I see patients. I see patients in a different group of exam rooms for their privacy and it’s a better setup for aspects of the physical encounter. Not a single patient has ever asked to come into my office and see my diplomas, and I sometimes wonder if I keep them here mostly as a visual cue to myself, sort of an antidote to ward off imposter syndrome and remind myself, Oh yeah – I earned these. I earned these through formal training.

Then something happens once you finish your training, whether it’s residency or fellowship, and you become an attending. I think you feel a weight of responsibility, the responsibility of independent learning. All of us are doing this. We have to do this. The field is moving along at such a rapid clip that it’s essentially built into what we do that we are going to keep up. In fact, channels such as the various aspects of social media are a way I curate my own information feed so I can stay up to speed and not feel like I’m drowning in a deluge of new data.

But what’s hard to demonstrate to the ABIM is that [this learning] is already happening. I think we can do it if we submit our records of CME credits that we formally accrue. The reason this is such an almost insult to oncologists in practice is because it is a necessary part of our day-to-day existence to keep apprised of developments so we can apply them to patient care.

One litmus test of attending a medical conference like the annual meeting of the American Society of Clinical Oncology is to ask oneself, When I go back to clinic, is this meeting going to change the way that I take care of patients? The answer almost invariably these days is yes. I go to multiple meetings per year, and I think it’s the exception, not the rule, that I return home and nothing changes in my management patterns. Again, this process is happening whether the ABIM recognizes it or not.

Lastly, I sat down in the fall of 2022 and I did my recertification. I looked at the span of all the things that had happened between 2012, when I first sat for my board examination in medical oncology, and 2022. It was staggering. I think the reason that it wasn’t such an overwhelming amount of information to review is that I had actually been accreting it slowly and gradually, month by month, year by year throughout that decade.

Again, it’s necessary that the ABIM hear us, hear oncologists, and know that of all the medical subspecialties they govern, it is basically already an essential task of our day-to-day professional existence that we engage in lifelong learning. To suggest otherwise really paints us as outdated. The reason that matters so much is that if we’re not up-to-date, then we are underserving our patients.

Mark A. Lewis, MD, is director of gastrointestinal oncology at Intermountain Healthcare in Salt Lake City. He reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

WASHINGTON – Multiple biologic failure in a minority of patients with psoriasis may have several causes, from genetic endotypes and immunologic factors to lower serum drug levels, the presence of anti-drug antibody levels, female sex, and certain comorbidities, Wilson Liao, MD, said at the annual research symposium of the National Psoriasis Foundation.

“Tough-to-treat psoriasis remains a challenge despite newer therapies ... Why do we still have this sub-population of patients who seem to be refractory?” said Dr. Liao, professor and associate vice chair of research in the department of dermatology at the University of California, San Francisco, who coauthored a 2015-2022 prospective cohort analysis that documented about 6% of patients failing two or more biologic agents of different mechanistic classes.

“These patients are really suffering,” he said. “We need to have better guidelines and treatment algorithms for these patients.”

A significant number of patients with psoriatic arthritis (PsA), meanwhile, are inadequate responders to tumor necrosis factor (TNF) inhibition, Christopher T. Ritchlin, MD, PhD, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), said during another session at the meeting.

The long-term “persistence,” or usage, of first-line biologics in patients with PsA – and of second-line biologics in patients who failed one TNF-inhibitor – is low, but the literature offers little information on the reasons for TNF-inhibitor discontinuation, said Dr. Ritchlin, who coauthored a perspective piece in Arthritis & Rheumatology on managing the patient with PsA who fails one TNF inhibitor.

Dr. Ritchlin and his coauthors were asked to provide evidence-informed advice and algorithms, but the task was difficult. “It’s hard to know what to recommend for the next step if we don’t know why patients failed the first,” he said. “The point is, we need more data. [Clinical trials] are not recording the kind of information we need.”
 

Anti-drug antibodies, genetics, other factors in psoriasis

Research shows that in large cohorts, “all the biologics do seem to lose efficacy over time,” said Dr. Liao, who directs the UCSF Psoriasis and Skin Treatment Center. “Some are better than others, but we do see a loss of effectiveness over time.”

A cohort study published in 2022 in JAMA Dermatology, for instance, documented declining “drug survival” associated with ineffectiveness during 2 years of treatment for each of five biologics studied (adalimumab [Humira], ustekinumab [Stelara], secukinumab [Cosentyx], guselkumab [Tremfya], and ixekizumab [Taltz]).

“There have been a number of theories put forward” as to why that’s the case, including lower serum drug levels, “which of course can be related to anti-drug antibody production,” he said.

He pointed to two studies of ustekinumab: One prospective observational cohort study that reported an association of lower early drug levels of the IL-12/23 receptor antagonist with lower Psoriasis Area and Severity Index (PASI) scores, and another observational study that documented an association between anti-drug antibody positivity with lower ustekinumab levels and impaired clinical response.

“We also now know ... that there are genetic endotypes in psoriasis, and that patients who are [HLA-C*06:02]-positive tend to respond a little better to drugs like ustekinumab, and those who are [HLA-C*06:02]-negative tend to do a little better with the TNF inhibitors,” Dr. Liao said. The human leukocyte antigen (HLA) allele HLA-C*06:02 is associated with susceptibility to psoriasis.

In a study using a national psoriasis registry, HLA-C*06:02-negative patients were 3 times more likely to achieve PASI90 status in response to adalimumab, a TNF-alpha inhibitor, than with ustekinumab treatment. And in a meta-analysis covering eight studies with more than 1,000 patients with psoriasis, the median PASI75 response rate after 6 months of ustekinumab therapy was 92% in the HLA-C*06:02-positive group and 67% in HLA-C*06:02-negative patients.

The recently published cohort study showing a 6% rate of multiple biologic failure evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for 2 or more years. Investigators looked for sociodemographic and clinical differences between the patients who continued use of their first biologic for at least 2 years (“good response”), and those who discontinued two or more biologics of different classes, each used for at least 90 days, because of inadequate efficacy.

Of 1,039 evaluated patients, 490 (47.2%) had good clinical response to their first biologic and 65 (6.3%) had multiple biologic failure. All biologic classes were represented among those who failed multiple biologics. The first and second biologic classes used were attempted for a mean duration of 10 months – “an adequate trial” of each, Dr. Liao said.

In multivariable regression analysis, six variables were significantly associated with multiple biologic failure: female sex at birth, shorter disease duration, earlier year of biologic initiation, prior nonbiologic systemic therapy, having Medicaid insurance, and a history of hyperlipidemia. The latter is “interesting because other studies have shown that metabolic syndrome, of which hyperlipidemia is a component, can also relate to poor response to biologics,” Dr. Liao said.

The most common sequences of first-to-second biologics among those with multiple biologic failure were TNF inhibitor to IL-17 inhibitor (30.8%); IL-12/23 inhibitor to IL-17 inhibitor (21.5%); TNF inhibitor to IL-12/23 inhibitor (12.3%); and IL-17 inhibitor to IL-23 inhibitor (10.8%).

The vast majority of patients failed more than two biologics, however, and “more than 20% had five or more biologics tried over a relatively short period,” Dr. Liao said.
 

Comorbidities and biologic failure in psoriasis, PsA

In practice, it was said during a discussion period, biologic failures in psoriasis can be of two types: a primary inadequate response or initial failure, or a secondary failure with initial improvement followed by declining or no response. “I agree 100% that these probably represent two different endotypes,” Dr. Liao said. “There’s research emerging that psoriasis isn’t necessarily a clean phenotype.”

The option of focusing on comorbidities in the face of biologic failure was another point of discussion. “Maybe the next biologic is not the answer,” a meeting participant said. “Maybe we should focus on metabolic syndrome.”

“I agree,” Dr. Liao said. “In clinic, there are people who may not respond to therapies but have other comorbidities and factors that make it difficult to manage [their psoriasis] ... that may be causative for psoriasis. Maybe if we treat the comorbidities, it will make it easier to treat the psoriasis.”

Addressing comorbidities and “extra-articular traits” such as poorly controlled diabetes, centralized pain, anxiety and depression, and obesity is something Dr. Ritchlin advocates for PsA. “Centralized pain, I believe, is a major driver of nonresponse,” he said at the meeting. “We have to be careful about blaming nonresponse and lack of efficacy of biologics when it could be a wholly different mechanism the biologic won’t treat ... for example, centralized pain.”

As with psoriasis, the emergence of antidrug antibodies may be one reason for the secondary failure of biologic agents for PsA, Dr. Ritchlin and his coauthors wrote in their paper on management of PsA after failure of one TNF inhibitor. Other areas to consider in evaluating failure, they wrote, are compliance and time of dosing, and financial barriers.

Low long-term persistence of second-line biologics for patients with PsA was demonstrated in a national cohort study utilizing the French health insurance database, Dr. Ritchlin noted at the research meeting. 

The French study covered almost 3,000 patients who started a second biologic after discontinuing a TNF inhibitor during 2015-2020. Overall, 1-year and 3-year persistence rates were 42% and 17%, respectively.

Dr. Liao disclosed research grant funding from AbbVie, Amgen, Janssen, Leo, Novartis, Pfizer, Regeneron, and Trex Bio. Dr. Ritchlin reported no disclosures.

WASHINGTON – Multiple biologic failure in a minority of patients with psoriasis may have several causes, from genetic endotypes and immunologic factors to lower serum drug levels, the presence of anti-drug antibody levels, female sex, and certain comorbidities, Wilson Liao, MD, said at the annual research symposium of the National Psoriasis Foundation.

“Tough-to-treat psoriasis remains a challenge despite newer therapies ... Why do we still have this sub-population of patients who seem to be refractory?” said Dr. Liao, professor and associate vice chair of research in the department of dermatology at the University of California, San Francisco, who coauthored a 2015-2022 prospective cohort analysis that documented about 6% of patients failing two or more biologic agents of different mechanistic classes.

“These patients are really suffering,” he said. “We need to have better guidelines and treatment algorithms for these patients.”

A significant number of patients with psoriatic arthritis (PsA), meanwhile, are inadequate responders to tumor necrosis factor (TNF) inhibition, Christopher T. Ritchlin, MD, PhD, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), said during another session at the meeting.

The long-term “persistence,” or usage, of first-line biologics in patients with PsA – and of second-line biologics in patients who failed one TNF-inhibitor – is low, but the literature offers little information on the reasons for TNF-inhibitor discontinuation, said Dr. Ritchlin, who coauthored a perspective piece in Arthritis & Rheumatology on managing the patient with PsA who fails one TNF inhibitor.

Dr. Ritchlin and his coauthors were asked to provide evidence-informed advice and algorithms, but the task was difficult. “It’s hard to know what to recommend for the next step if we don’t know why patients failed the first,” he said. “The point is, we need more data. [Clinical trials] are not recording the kind of information we need.”
 

Anti-drug antibodies, genetics, other factors in psoriasis

Research shows that in large cohorts, “all the biologics do seem to lose efficacy over time,” said Dr. Liao, who directs the UCSF Psoriasis and Skin Treatment Center. “Some are better than others, but we do see a loss of effectiveness over time.”

A cohort study published in 2022 in JAMA Dermatology, for instance, documented declining “drug survival” associated with ineffectiveness during 2 years of treatment for each of five biologics studied (adalimumab [Humira], ustekinumab [Stelara], secukinumab [Cosentyx], guselkumab [Tremfya], and ixekizumab [Taltz]).

“There have been a number of theories put forward” as to why that’s the case, including lower serum drug levels, “which of course can be related to anti-drug antibody production,” he said.

He pointed to two studies of ustekinumab: One prospective observational cohort study that reported an association of lower early drug levels of the IL-12/23 receptor antagonist with lower Psoriasis Area and Severity Index (PASI) scores, and another observational study that documented an association between anti-drug antibody positivity with lower ustekinumab levels and impaired clinical response.

“We also now know ... that there are genetic endotypes in psoriasis, and that patients who are [HLA-C*06:02]-positive tend to respond a little better to drugs like ustekinumab, and those who are [HLA-C*06:02]-negative tend to do a little better with the TNF inhibitors,” Dr. Liao said. The human leukocyte antigen (HLA) allele HLA-C*06:02 is associated with susceptibility to psoriasis.

In a study using a national psoriasis registry, HLA-C*06:02-negative patients were 3 times more likely to achieve PASI90 status in response to adalimumab, a TNF-alpha inhibitor, than with ustekinumab treatment. And in a meta-analysis covering eight studies with more than 1,000 patients with psoriasis, the median PASI75 response rate after 6 months of ustekinumab therapy was 92% in the HLA-C*06:02-positive group and 67% in HLA-C*06:02-negative patients.

The recently published cohort study showing a 6% rate of multiple biologic failure evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for 2 or more years. Investigators looked for sociodemographic and clinical differences between the patients who continued use of their first biologic for at least 2 years (“good response”), and those who discontinued two or more biologics of different classes, each used for at least 90 days, because of inadequate efficacy.

Of 1,039 evaluated patients, 490 (47.2%) had good clinical response to their first biologic and 65 (6.3%) had multiple biologic failure. All biologic classes were represented among those who failed multiple biologics. The first and second biologic classes used were attempted for a mean duration of 10 months – “an adequate trial” of each, Dr. Liao said.

In multivariable regression analysis, six variables were significantly associated with multiple biologic failure: female sex at birth, shorter disease duration, earlier year of biologic initiation, prior nonbiologic systemic therapy, having Medicaid insurance, and a history of hyperlipidemia. The latter is “interesting because other studies have shown that metabolic syndrome, of which hyperlipidemia is a component, can also relate to poor response to biologics,” Dr. Liao said.

The most common sequences of first-to-second biologics among those with multiple biologic failure were TNF inhibitor to IL-17 inhibitor (30.8%); IL-12/23 inhibitor to IL-17 inhibitor (21.5%); TNF inhibitor to IL-12/23 inhibitor (12.3%); and IL-17 inhibitor to IL-23 inhibitor (10.8%).

The vast majority of patients failed more than two biologics, however, and “more than 20% had five or more biologics tried over a relatively short period,” Dr. Liao said.
 

Comorbidities and biologic failure in psoriasis, PsA

In practice, it was said during a discussion period, biologic failures in psoriasis can be of two types: a primary inadequate response or initial failure, or a secondary failure with initial improvement followed by declining or no response. “I agree 100% that these probably represent two different endotypes,” Dr. Liao said. “There’s research emerging that psoriasis isn’t necessarily a clean phenotype.”

The option of focusing on comorbidities in the face of biologic failure was another point of discussion. “Maybe the next biologic is not the answer,” a meeting participant said. “Maybe we should focus on metabolic syndrome.”

“I agree,” Dr. Liao said. “In clinic, there are people who may not respond to therapies but have other comorbidities and factors that make it difficult to manage [their psoriasis] ... that may be causative for psoriasis. Maybe if we treat the comorbidities, it will make it easier to treat the psoriasis.”

Addressing comorbidities and “extra-articular traits” such as poorly controlled diabetes, centralized pain, anxiety and depression, and obesity is something Dr. Ritchlin advocates for PsA. “Centralized pain, I believe, is a major driver of nonresponse,” he said at the meeting. “We have to be careful about blaming nonresponse and lack of efficacy of biologics when it could be a wholly different mechanism the biologic won’t treat ... for example, centralized pain.”

As with psoriasis, the emergence of antidrug antibodies may be one reason for the secondary failure of biologic agents for PsA, Dr. Ritchlin and his coauthors wrote in their paper on management of PsA after failure of one TNF inhibitor. Other areas to consider in evaluating failure, they wrote, are compliance and time of dosing, and financial barriers.

Low long-term persistence of second-line biologics for patients with PsA was demonstrated in a national cohort study utilizing the French health insurance database, Dr. Ritchlin noted at the research meeting. 

The French study covered almost 3,000 patients who started a second biologic after discontinuing a TNF inhibitor during 2015-2020. Overall, 1-year and 3-year persistence rates were 42% and 17%, respectively.

Dr. Liao disclosed research grant funding from AbbVie, Amgen, Janssen, Leo, Novartis, Pfizer, Regeneron, and Trex Bio. Dr. Ritchlin reported no disclosures.

WASHINGTON – Multiple biologic failure in a minority of patients with psoriasis may have several causes, from genetic endotypes and immunologic factors to lower serum drug levels, the presence of anti-drug antibody levels, female sex, and certain comorbidities, Wilson Liao, MD, said at the annual research symposium of the National Psoriasis Foundation.

“Tough-to-treat psoriasis remains a challenge despite newer therapies ... Why do we still have this sub-population of patients who seem to be refractory?” said Dr. Liao, professor and associate vice chair of research in the department of dermatology at the University of California, San Francisco, who coauthored a 2015-2022 prospective cohort analysis that documented about 6% of patients failing two or more biologic agents of different mechanistic classes.

“These patients are really suffering,” he said. “We need to have better guidelines and treatment algorithms for these patients.”

A significant number of patients with psoriatic arthritis (PsA), meanwhile, are inadequate responders to tumor necrosis factor (TNF) inhibition, Christopher T. Ritchlin, MD, PhD, professor of medicine in the division of allergy/immunology and rheumatology and the Center of Musculoskeletal Research at the University of Rochester (N.Y.), said during another session at the meeting.

The long-term “persistence,” or usage, of first-line biologics in patients with PsA – and of second-line biologics in patients who failed one TNF-inhibitor – is low, but the literature offers little information on the reasons for TNF-inhibitor discontinuation, said Dr. Ritchlin, who coauthored a perspective piece in Arthritis & Rheumatology on managing the patient with PsA who fails one TNF inhibitor.

Dr. Ritchlin and his coauthors were asked to provide evidence-informed advice and algorithms, but the task was difficult. “It’s hard to know what to recommend for the next step if we don’t know why patients failed the first,” he said. “The point is, we need more data. [Clinical trials] are not recording the kind of information we need.”
 

Anti-drug antibodies, genetics, other factors in psoriasis

Research shows that in large cohorts, “all the biologics do seem to lose efficacy over time,” said Dr. Liao, who directs the UCSF Psoriasis and Skin Treatment Center. “Some are better than others, but we do see a loss of effectiveness over time.”

A cohort study published in 2022 in JAMA Dermatology, for instance, documented declining “drug survival” associated with ineffectiveness during 2 years of treatment for each of five biologics studied (adalimumab [Humira], ustekinumab [Stelara], secukinumab [Cosentyx], guselkumab [Tremfya], and ixekizumab [Taltz]).

“There have been a number of theories put forward” as to why that’s the case, including lower serum drug levels, “which of course can be related to anti-drug antibody production,” he said.

He pointed to two studies of ustekinumab: One prospective observational cohort study that reported an association of lower early drug levels of the IL-12/23 receptor antagonist with lower Psoriasis Area and Severity Index (PASI) scores, and another observational study that documented an association between anti-drug antibody positivity with lower ustekinumab levels and impaired clinical response.

“We also now know ... that there are genetic endotypes in psoriasis, and that patients who are [HLA-C*06:02]-positive tend to respond a little better to drugs like ustekinumab, and those who are [HLA-C*06:02]-negative tend to do a little better with the TNF inhibitors,” Dr. Liao said. The human leukocyte antigen (HLA) allele HLA-C*06:02 is associated with susceptibility to psoriasis.

In a study using a national psoriasis registry, HLA-C*06:02-negative patients were 3 times more likely to achieve PASI90 status in response to adalimumab, a TNF-alpha inhibitor, than with ustekinumab treatment. And in a meta-analysis covering eight studies with more than 1,000 patients with psoriasis, the median PASI75 response rate after 6 months of ustekinumab therapy was 92% in the HLA-C*06:02-positive group and 67% in HLA-C*06:02-negative patients.

The recently published cohort study showing a 6% rate of multiple biologic failure evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for 2 or more years. Investigators looked for sociodemographic and clinical differences between the patients who continued use of their first biologic for at least 2 years (“good response”), and those who discontinued two or more biologics of different classes, each used for at least 90 days, because of inadequate efficacy.

Of 1,039 evaluated patients, 490 (47.2%) had good clinical response to their first biologic and 65 (6.3%) had multiple biologic failure. All biologic classes were represented among those who failed multiple biologics. The first and second biologic classes used were attempted for a mean duration of 10 months – “an adequate trial” of each, Dr. Liao said.

In multivariable regression analysis, six variables were significantly associated with multiple biologic failure: female sex at birth, shorter disease duration, earlier year of biologic initiation, prior nonbiologic systemic therapy, having Medicaid insurance, and a history of hyperlipidemia. The latter is “interesting because other studies have shown that metabolic syndrome, of which hyperlipidemia is a component, can also relate to poor response to biologics,” Dr. Liao said.

The most common sequences of first-to-second biologics among those with multiple biologic failure were TNF inhibitor to IL-17 inhibitor (30.8%); IL-12/23 inhibitor to IL-17 inhibitor (21.5%); TNF inhibitor to IL-12/23 inhibitor (12.3%); and IL-17 inhibitor to IL-23 inhibitor (10.8%).

The vast majority of patients failed more than two biologics, however, and “more than 20% had five or more biologics tried over a relatively short period,” Dr. Liao said.
 

Comorbidities and biologic failure in psoriasis, PsA

In practice, it was said during a discussion period, biologic failures in psoriasis can be of two types: a primary inadequate response or initial failure, or a secondary failure with initial improvement followed by declining or no response. “I agree 100% that these probably represent two different endotypes,” Dr. Liao said. “There’s research emerging that psoriasis isn’t necessarily a clean phenotype.”

The option of focusing on comorbidities in the face of biologic failure was another point of discussion. “Maybe the next biologic is not the answer,” a meeting participant said. “Maybe we should focus on metabolic syndrome.”

“I agree,” Dr. Liao said. “In clinic, there are people who may not respond to therapies but have other comorbidities and factors that make it difficult to manage [their psoriasis] ... that may be causative for psoriasis. Maybe if we treat the comorbidities, it will make it easier to treat the psoriasis.”

Addressing comorbidities and “extra-articular traits” such as poorly controlled diabetes, centralized pain, anxiety and depression, and obesity is something Dr. Ritchlin advocates for PsA. “Centralized pain, I believe, is a major driver of nonresponse,” he said at the meeting. “We have to be careful about blaming nonresponse and lack of efficacy of biologics when it could be a wholly different mechanism the biologic won’t treat ... for example, centralized pain.”

As with psoriasis, the emergence of antidrug antibodies may be one reason for the secondary failure of biologic agents for PsA, Dr. Ritchlin and his coauthors wrote in their paper on management of PsA after failure of one TNF inhibitor. Other areas to consider in evaluating failure, they wrote, are compliance and time of dosing, and financial barriers.

Low long-term persistence of second-line biologics for patients with PsA was demonstrated in a national cohort study utilizing the French health insurance database, Dr. Ritchlin noted at the research meeting. 

The French study covered almost 3,000 patients who started a second biologic after discontinuing a TNF inhibitor during 2015-2020. Overall, 1-year and 3-year persistence rates were 42% and 17%, respectively.

Dr. Liao disclosed research grant funding from AbbVie, Amgen, Janssen, Leo, Novartis, Pfizer, Regeneron, and Trex Bio. Dr. Ritchlin reported no disclosures.

Could antidepressants hold the key to treating long COVID? University of Pennsylvania researchers have uncovered a link between long COVID and levels of serotonin in the body that may offer a new explanation for the condition. The study even points to a possible treatment.

Serotonin is a neurotransmitter that has many functions in the body and is targeted by the most commonly prescribed antidepressants – the selective serotonin reuptake inhibitors.

Serotonin is widely studied for its effects on the brain – it regulates the messaging between neurons, affecting sleep, mood, and memory. It is present in the gut, is found in cells along the gastrointestinal tract, and is absorbed by blood platelets. Gut serotonin, known as circulating serotonin, is responsible for a host of other functions, including the regulation of blood flow, body temperature, and digestion.

Low levels of serotonin could result in any number of seemingly unrelated symptoms, as in the case of long COVID, experts say. The condition affects about 7% of Americans and is associated with a wide range of health problems, including fatigue, shortness of breath, neurological symptoms, joint pain, blood clots, heart palpitations, and digestive problems.

Long COVID is difficult to treat because researchers haven’t been able to pinpoint the underlying mechanisms that cause prolonged illness after a SARS-CoV-2 infection, said study author Christoph A. Thaiss, PhD, an assistant professor of microbiology at the Perelman School of Medicine at the University of Pennsylvania.

The hope is that this study could have implications for new treatments, he said.

“Long COVID can have manifestations not only in the brain but in many different parts of the body, so it’s possible that serotonin reductions are involved in many different aspects of the disease,” said Dr. Thaiss.

Dr. Thaiss’s study, published in the journal Cell, found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but who fully recovered.

His team found that reductions in serotonin were driven by low levels of circulating SARS-CoV-2 virus that caused persistent inflammation as well as an inability of the body to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactive blood platelets were also shown to play a role; they serve as the primary means of serotonin absorption.

The study doesn’t make any recommendations for treatment, but understanding the role of serotonin in long COVID opens the door to a host of novel ideas that could set the stage for clinical trials and affect care.

“The study gives us a few possible targets that could be used in future clinical studies,” Dr. Thaiss said.

Persistent circulating virus is one of the drivers of low serotonin levels, said study author Michael Peluso, MD, an assistant research professor of infectious medicine at the University of California, San Francisco, School of Medicine. This points to the need to reduce viral load using antiviral medications like nirmatrelvir/ritonavir (Paxlovid), which is approved by the U.S. Food and Drug Administration for the treatment of COVID-19, and VV116, which has not yet been approved for use against COVID.

Research published in the New England Journal of Medicine found that the oral antiviral agent VV116 was as effective as nirmatrelvir/ritonavir in reducing the body’s viral load and aiding recovery from SARS-CoV-2 infection. Paxlovid has also been shown to reduce the likelihood of getting long COVID after an acute SARS-CoV-2 infection.

Researchers are investigating ways to target serotonin levels directly, potentially using SSRIs. But first they need to study whether improvement in serotonin level makes a difference.

“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said.

Indeed, the research did show that the SSRI fluoxetine, as well as a glycine-tryptophan supplement, improved cognitive function in SARS-CoV-2-infected rodent models, which were used in a portion of the study.

David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City, said the research is helping “to paint a biological picture” that’s in line with other research on the mechanisms that cause long COVID symptoms.

But Dr. Putrino, who was not involved in the study, cautions against treating long COVID patients with SSRIs or any other treatment that increases serotonin before testing patients to determine whether their serotonin levels are actually lower than those of healthy persons.

“We don’t want to assume that every patient with long COVID is going to have lower serotonin levels,” said Dr. Putrino.

What’s more, researchers need to investigate whether SSRIs increase levels of circulating serotonin. It’s important to note that researchers found lower levels of circulating serotonin but that serotonin levels in the brain remained normal.

Traditionally, SSRIs are used clinically for increasing the levels of serotonin in the brain, not the body.

“Whether that’s going to contribute to an increase in systemic levels of serotonin, that’s something that needs to be tested,” said Akiko Iwasaki, PhD, co-lead investigator of the Yale School of Medicine, New Haven, Conn., COVID-19 Recovery Study, who was not involved in the research.

Thus far, investigators have not identified one unifying biomarker that seems to cause long COVID in all patients, said Dr. Iwasaki. Some research has found higher levels of certain immune cells and biomarkers: for example, monocytes and activated B lymphocytes, indicating a stronger and ongoing antibody response to the virus. Other recent research conducted by Dr. Iwasaki, Dr. Putrino, and others, published in the journal Nature, showed that long COVID patients tend to have lower levels of cortisol, which could be a factor in the extreme fatigue experienced by many who suffer from the condition.

The findings in the study in The Cell are promising, but they need to be replicated in more people, said Dr. Iwasaki. And even if they’re replicated in a larger study population, this would still be just one biomarker that is associated with one subtype of the disease. There is a need to better understand which biomarkers go with which symptoms so that the most effective treatments can be identified, she said.

Both Dr. Putrino and Dr. Iwasaki contended that there isn’t a single factor that can explain all of long COVID. It’s a complex disease caused by a host of different mechanisms.

Still, low levels of serotonin could be an important piece of the puzzle. The next step, said Dr. Iwasaki, is to uncover how many of the millions of Americans with long COVID have this biomarker.

“People working in the field of long COVID should now be considering this pathway and thinking of ways to measure serotonin in their patients.”

A version of this article first appeared on Medscape.com.

Could antidepressants hold the key to treating long COVID? University of Pennsylvania researchers have uncovered a link between long COVID and levels of serotonin in the body that may offer a new explanation for the condition. The study even points to a possible treatment.

Serotonin is a neurotransmitter that has many functions in the body and is targeted by the most commonly prescribed antidepressants – the selective serotonin reuptake inhibitors.

Serotonin is widely studied for its effects on the brain – it regulates the messaging between neurons, affecting sleep, mood, and memory. It is present in the gut, is found in cells along the gastrointestinal tract, and is absorbed by blood platelets. Gut serotonin, known as circulating serotonin, is responsible for a host of other functions, including the regulation of blood flow, body temperature, and digestion.

Low levels of serotonin could result in any number of seemingly unrelated symptoms, as in the case of long COVID, experts say. The condition affects about 7% of Americans and is associated with a wide range of health problems, including fatigue, shortness of breath, neurological symptoms, joint pain, blood clots, heart palpitations, and digestive problems.

Long COVID is difficult to treat because researchers haven’t been able to pinpoint the underlying mechanisms that cause prolonged illness after a SARS-CoV-2 infection, said study author Christoph A. Thaiss, PhD, an assistant professor of microbiology at the Perelman School of Medicine at the University of Pennsylvania.

The hope is that this study could have implications for new treatments, he said.

“Long COVID can have manifestations not only in the brain but in many different parts of the body, so it’s possible that serotonin reductions are involved in many different aspects of the disease,” said Dr. Thaiss.

Dr. Thaiss’s study, published in the journal Cell, found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but who fully recovered.

His team found that reductions in serotonin were driven by low levels of circulating SARS-CoV-2 virus that caused persistent inflammation as well as an inability of the body to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactive blood platelets were also shown to play a role; they serve as the primary means of serotonin absorption.

The study doesn’t make any recommendations for treatment, but understanding the role of serotonin in long COVID opens the door to a host of novel ideas that could set the stage for clinical trials and affect care.

“The study gives us a few possible targets that could be used in future clinical studies,” Dr. Thaiss said.

Persistent circulating virus is one of the drivers of low serotonin levels, said study author Michael Peluso, MD, an assistant research professor of infectious medicine at the University of California, San Francisco, School of Medicine. This points to the need to reduce viral load using antiviral medications like nirmatrelvir/ritonavir (Paxlovid), which is approved by the U.S. Food and Drug Administration for the treatment of COVID-19, and VV116, which has not yet been approved for use against COVID.

Research published in the New England Journal of Medicine found that the oral antiviral agent VV116 was as effective as nirmatrelvir/ritonavir in reducing the body’s viral load and aiding recovery from SARS-CoV-2 infection. Paxlovid has also been shown to reduce the likelihood of getting long COVID after an acute SARS-CoV-2 infection.

Researchers are investigating ways to target serotonin levels directly, potentially using SSRIs. But first they need to study whether improvement in serotonin level makes a difference.

“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said.

Indeed, the research did show that the SSRI fluoxetine, as well as a glycine-tryptophan supplement, improved cognitive function in SARS-CoV-2-infected rodent models, which were used in a portion of the study.

David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City, said the research is helping “to paint a biological picture” that’s in line with other research on the mechanisms that cause long COVID symptoms.

But Dr. Putrino, who was not involved in the study, cautions against treating long COVID patients with SSRIs or any other treatment that increases serotonin before testing patients to determine whether their serotonin levels are actually lower than those of healthy persons.

“We don’t want to assume that every patient with long COVID is going to have lower serotonin levels,” said Dr. Putrino.

What’s more, researchers need to investigate whether SSRIs increase levels of circulating serotonin. It’s important to note that researchers found lower levels of circulating serotonin but that serotonin levels in the brain remained normal.

Traditionally, SSRIs are used clinically for increasing the levels of serotonin in the brain, not the body.

“Whether that’s going to contribute to an increase in systemic levels of serotonin, that’s something that needs to be tested,” said Akiko Iwasaki, PhD, co-lead investigator of the Yale School of Medicine, New Haven, Conn., COVID-19 Recovery Study, who was not involved in the research.

Thus far, investigators have not identified one unifying biomarker that seems to cause long COVID in all patients, said Dr. Iwasaki. Some research has found higher levels of certain immune cells and biomarkers: for example, monocytes and activated B lymphocytes, indicating a stronger and ongoing antibody response to the virus. Other recent research conducted by Dr. Iwasaki, Dr. Putrino, and others, published in the journal Nature, showed that long COVID patients tend to have lower levels of cortisol, which could be a factor in the extreme fatigue experienced by many who suffer from the condition.

The findings in the study in The Cell are promising, but they need to be replicated in more people, said Dr. Iwasaki. And even if they’re replicated in a larger study population, this would still be just one biomarker that is associated with one subtype of the disease. There is a need to better understand which biomarkers go with which symptoms so that the most effective treatments can be identified, she said.

Both Dr. Putrino and Dr. Iwasaki contended that there isn’t a single factor that can explain all of long COVID. It’s a complex disease caused by a host of different mechanisms.

Still, low levels of serotonin could be an important piece of the puzzle. The next step, said Dr. Iwasaki, is to uncover how many of the millions of Americans with long COVID have this biomarker.

“People working in the field of long COVID should now be considering this pathway and thinking of ways to measure serotonin in their patients.”

A version of this article first appeared on Medscape.com.

Could antidepressants hold the key to treating long COVID? University of Pennsylvania researchers have uncovered a link between long COVID and levels of serotonin in the body that may offer a new explanation for the condition. The study even points to a possible treatment.

Serotonin is a neurotransmitter that has many functions in the body and is targeted by the most commonly prescribed antidepressants – the selective serotonin reuptake inhibitors.

Serotonin is widely studied for its effects on the brain – it regulates the messaging between neurons, affecting sleep, mood, and memory. It is present in the gut, is found in cells along the gastrointestinal tract, and is absorbed by blood platelets. Gut serotonin, known as circulating serotonin, is responsible for a host of other functions, including the regulation of blood flow, body temperature, and digestion.

Low levels of serotonin could result in any number of seemingly unrelated symptoms, as in the case of long COVID, experts say. The condition affects about 7% of Americans and is associated with a wide range of health problems, including fatigue, shortness of breath, neurological symptoms, joint pain, blood clots, heart palpitations, and digestive problems.

Long COVID is difficult to treat because researchers haven’t been able to pinpoint the underlying mechanisms that cause prolonged illness after a SARS-CoV-2 infection, said study author Christoph A. Thaiss, PhD, an assistant professor of microbiology at the Perelman School of Medicine at the University of Pennsylvania.

The hope is that this study could have implications for new treatments, he said.

“Long COVID can have manifestations not only in the brain but in many different parts of the body, so it’s possible that serotonin reductions are involved in many different aspects of the disease,” said Dr. Thaiss.

Dr. Thaiss’s study, published in the journal Cell, found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but who fully recovered.

His team found that reductions in serotonin were driven by low levels of circulating SARS-CoV-2 virus that caused persistent inflammation as well as an inability of the body to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactive blood platelets were also shown to play a role; they serve as the primary means of serotonin absorption.

The study doesn’t make any recommendations for treatment, but understanding the role of serotonin in long COVID opens the door to a host of novel ideas that could set the stage for clinical trials and affect care.

“The study gives us a few possible targets that could be used in future clinical studies,” Dr. Thaiss said.

Persistent circulating virus is one of the drivers of low serotonin levels, said study author Michael Peluso, MD, an assistant research professor of infectious medicine at the University of California, San Francisco, School of Medicine. This points to the need to reduce viral load using antiviral medications like nirmatrelvir/ritonavir (Paxlovid), which is approved by the U.S. Food and Drug Administration for the treatment of COVID-19, and VV116, which has not yet been approved for use against COVID.

Research published in the New England Journal of Medicine found that the oral antiviral agent VV116 was as effective as nirmatrelvir/ritonavir in reducing the body’s viral load and aiding recovery from SARS-CoV-2 infection. Paxlovid has also been shown to reduce the likelihood of getting long COVID after an acute SARS-CoV-2 infection.

Researchers are investigating ways to target serotonin levels directly, potentially using SSRIs. But first they need to study whether improvement in serotonin level makes a difference.

“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said.

Indeed, the research did show that the SSRI fluoxetine, as well as a glycine-tryptophan supplement, improved cognitive function in SARS-CoV-2-infected rodent models, which were used in a portion of the study.

David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City, said the research is helping “to paint a biological picture” that’s in line with other research on the mechanisms that cause long COVID symptoms.

But Dr. Putrino, who was not involved in the study, cautions against treating long COVID patients with SSRIs or any other treatment that increases serotonin before testing patients to determine whether their serotonin levels are actually lower than those of healthy persons.

“We don’t want to assume that every patient with long COVID is going to have lower serotonin levels,” said Dr. Putrino.

What’s more, researchers need to investigate whether SSRIs increase levels of circulating serotonin. It’s important to note that researchers found lower levels of circulating serotonin but that serotonin levels in the brain remained normal.

Traditionally, SSRIs are used clinically for increasing the levels of serotonin in the brain, not the body.

“Whether that’s going to contribute to an increase in systemic levels of serotonin, that’s something that needs to be tested,” said Akiko Iwasaki, PhD, co-lead investigator of the Yale School of Medicine, New Haven, Conn., COVID-19 Recovery Study, who was not involved in the research.

Thus far, investigators have not identified one unifying biomarker that seems to cause long COVID in all patients, said Dr. Iwasaki. Some research has found higher levels of certain immune cells and biomarkers: for example, monocytes and activated B lymphocytes, indicating a stronger and ongoing antibody response to the virus. Other recent research conducted by Dr. Iwasaki, Dr. Putrino, and others, published in the journal Nature, showed that long COVID patients tend to have lower levels of cortisol, which could be a factor in the extreme fatigue experienced by many who suffer from the condition.

The findings in the study in The Cell are promising, but they need to be replicated in more people, said Dr. Iwasaki. And even if they’re replicated in a larger study population, this would still be just one biomarker that is associated with one subtype of the disease. There is a need to better understand which biomarkers go with which symptoms so that the most effective treatments can be identified, she said.

Both Dr. Putrino and Dr. Iwasaki contended that there isn’t a single factor that can explain all of long COVID. It’s a complex disease caused by a host of different mechanisms.

Still, low levels of serotonin could be an important piece of the puzzle. The next step, said Dr. Iwasaki, is to uncover how many of the millions of Americans with long COVID have this biomarker.

“People working in the field of long COVID should now be considering this pathway and thinking of ways to measure serotonin in their patients.”

A version of this article first appeared on Medscape.com.

People infected multiple times with COVID-19 are more likely to develop long COVID, and most never fully recover from the condition. Those are two of the most striking findings of a comprehensive new research study of 138,000 veterans.

Lead researcher Ziyad Al-Aly, MD, chief of research at Veterans Affairs St. Louis Health Care and clinical epidemiologist at Washington University in St. Louis, spoke with this news organization about his team’s findings, what we know – and don’t – about long COVID, and what it means for physicians treating patients with the condition.

Excerpts of the interview follow.

Your research concluded that for those infected early in the pandemic, some long COVID symptoms declined over 2 years, but some did not. You have also concluded that long COVID is a chronic disease. Why?

We’ve been in this journey a little bit more than three and a half years. Some patients do experience some recovery. But that’s not the norm. Most people do not really fully recover. The health trajectory for people with long COVID is really very heterogeneous. There is no one-size-fits-all. There’s really no one line that I could give you that could cover all your patients. But it is very, very, very clear that a bunch of them experienced long COVID for sure; that’s really happening.

It happened in the pre-Delta era and in the Delta era, and with Omicron subvariants, even now. There are people who think, “This is a nothing-burger anymore,” or “It’s not an issue anymore.” It’s still happening with the current variants. Vaccines do reduce risk for long COVID, but do not completely eliminate the risk for long COVID.

You work with patients with long COVID in the clinic and also analyze data from thousands more. If long COVID does not go away, what should doctors look for in everyday practice that will help them recognize and help patients with long COVID?

Long COVID is not uncommon. We see it in the clinic in large numbers. Whatever clinic you’re running – if you’re running a cardiology clinic, or a nephrology clinic, or diabetes, or primary care – probably some of your people have it. You may not know about it. They may not tell you about it. You may not recognize it.

Not all long COVID is the same, and that’s really what makes it complex and makes it really hard to deal with in the clinic. But that’s the reality that we’re all dealing with. And it’s multisystemic; it’s not like it affects the heart only, the brain only, or the autonomic nervous system only. It does not behave in the same way in different individuals – they may have different manifestations, various health trajectories, and different outcomes. It’s important for doctors to get up to speed on long COVID as a multisystem illness.

Management at this point is really managing the symptoms. We don’t have a treatment for it; we don’t have a cure for it.

Some patients experience what you’ve described as partial recovery. What does that look like?

Some individuals do experience some recovery over time, but for most individuals, the recovery is long and arduous. Long COVID can last with them for many years. Some people may come back to the clinic and say, “I’m doing better,” but if you really flesh it out and dig deeper, they didn’t do better; they adjusted to a new baseline. They used to walk the dog three to four blocks, and now they walk the dog only half a block. They used to do an activity with their partner every Saturday or Sunday, and now they do half of that.

If you’re a physician, a primary care provider, or any other provider who is dealing with a patient with long COVID, know that this is really happening. It can happen even in vaccinated individuals. The presentation is heterogeneous. Some people may present to you with and say. “Well, before I had COVID I was mentally sharp and now having I’m having difficulty with memory, etc.” It can sometimes present as fatigue or postexertional malaise.

In some instances, it can present as sleep problems. It can present as what we call postural orthostatic tachycardia syndrome (POTS). Those people get a significant increase in heart rate with postural changes.

What the most important thing we can we learn from the emergence of long COVID?

This whole thing taught us that infections can cause chronic disease. That’s really the No. 1 lesson that I take from this pandemic – that infections can cause chronic disease.

Looking at only acute illness from COVID is really only looking at the tip of the iceberg. Beneath that tip of the iceberg lies this hidden toll of disease that we don’t really talk about that much.

This pandemic shone a very, very good light on the idea that there is really an intimate connection between infections and chronic disease. It was really hardwired into our medical training as doctors that most infections, when people get over the hump of the acute phase of the disease, it’s all behind them. I think long COVID has humbled us in many, many ways, but chief among those is the realization – the stark realization – that infections can cause chronic disease.

That’s really going back to your [first] question: What does it mean that some people are not recovering? They actually have chronic illness. I’m hoping that we will find a treatment, that we’ll start finding things that would help them get back to baseline. But at this point in time, what we’re dealing with is people with chronic illness or chronic disease that may continue to affect them for many years to come in the absence of a treatment or a cure.

A version of this article first appeared on Medscape.com.

People infected multiple times with COVID-19 are more likely to develop long COVID, and most never fully recover from the condition. Those are two of the most striking findings of a comprehensive new research study of 138,000 veterans.

Lead researcher Ziyad Al-Aly, MD, chief of research at Veterans Affairs St. Louis Health Care and clinical epidemiologist at Washington University in St. Louis, spoke with this news organization about his team’s findings, what we know – and don’t – about long COVID, and what it means for physicians treating patients with the condition.

Excerpts of the interview follow.

Your research concluded that for those infected early in the pandemic, some long COVID symptoms declined over 2 years, but some did not. You have also concluded that long COVID is a chronic disease. Why?

We’ve been in this journey a little bit more than three and a half years. Some patients do experience some recovery. But that’s not the norm. Most people do not really fully recover. The health trajectory for people with long COVID is really very heterogeneous. There is no one-size-fits-all. There’s really no one line that I could give you that could cover all your patients. But it is very, very, very clear that a bunch of them experienced long COVID for sure; that’s really happening.

It happened in the pre-Delta era and in the Delta era, and with Omicron subvariants, even now. There are people who think, “This is a nothing-burger anymore,” or “It’s not an issue anymore.” It’s still happening with the current variants. Vaccines do reduce risk for long COVID, but do not completely eliminate the risk for long COVID.

You work with patients with long COVID in the clinic and also analyze data from thousands more. If long COVID does not go away, what should doctors look for in everyday practice that will help them recognize and help patients with long COVID?

Long COVID is not uncommon. We see it in the clinic in large numbers. Whatever clinic you’re running – if you’re running a cardiology clinic, or a nephrology clinic, or diabetes, or primary care – probably some of your people have it. You may not know about it. They may not tell you about it. You may not recognize it.

Not all long COVID is the same, and that’s really what makes it complex and makes it really hard to deal with in the clinic. But that’s the reality that we’re all dealing with. And it’s multisystemic; it’s not like it affects the heart only, the brain only, or the autonomic nervous system only. It does not behave in the same way in different individuals – they may have different manifestations, various health trajectories, and different outcomes. It’s important for doctors to get up to speed on long COVID as a multisystem illness.

Management at this point is really managing the symptoms. We don’t have a treatment for it; we don’t have a cure for it.

Some patients experience what you’ve described as partial recovery. What does that look like?

Some individuals do experience some recovery over time, but for most individuals, the recovery is long and arduous. Long COVID can last with them for many years. Some people may come back to the clinic and say, “I’m doing better,” but if you really flesh it out and dig deeper, they didn’t do better; they adjusted to a new baseline. They used to walk the dog three to four blocks, and now they walk the dog only half a block. They used to do an activity with their partner every Saturday or Sunday, and now they do half of that.

If you’re a physician, a primary care provider, or any other provider who is dealing with a patient with long COVID, know that this is really happening. It can happen even in vaccinated individuals. The presentation is heterogeneous. Some people may present to you with and say. “Well, before I had COVID I was mentally sharp and now having I’m having difficulty with memory, etc.” It can sometimes present as fatigue or postexertional malaise.

In some instances, it can present as sleep problems. It can present as what we call postural orthostatic tachycardia syndrome (POTS). Those people get a significant increase in heart rate with postural changes.

What the most important thing we can we learn from the emergence of long COVID?

This whole thing taught us that infections can cause chronic disease. That’s really the No. 1 lesson that I take from this pandemic – that infections can cause chronic disease.

Looking at only acute illness from COVID is really only looking at the tip of the iceberg. Beneath that tip of the iceberg lies this hidden toll of disease that we don’t really talk about that much.

This pandemic shone a very, very good light on the idea that there is really an intimate connection between infections and chronic disease. It was really hardwired into our medical training as doctors that most infections, when people get over the hump of the acute phase of the disease, it’s all behind them. I think long COVID has humbled us in many, many ways, but chief among those is the realization – the stark realization – that infections can cause chronic disease.

That’s really going back to your [first] question: What does it mean that some people are not recovering? They actually have chronic illness. I’m hoping that we will find a treatment, that we’ll start finding things that would help them get back to baseline. But at this point in time, what we’re dealing with is people with chronic illness or chronic disease that may continue to affect them for many years to come in the absence of a treatment or a cure.

A version of this article first appeared on Medscape.com.

People infected multiple times with COVID-19 are more likely to develop long COVID, and most never fully recover from the condition. Those are two of the most striking findings of a comprehensive new research study of 138,000 veterans.

Lead researcher Ziyad Al-Aly, MD, chief of research at Veterans Affairs St. Louis Health Care and clinical epidemiologist at Washington University in St. Louis, spoke with this news organization about his team’s findings, what we know – and don’t – about long COVID, and what it means for physicians treating patients with the condition.

Excerpts of the interview follow.

Your research concluded that for those infected early in the pandemic, some long COVID symptoms declined over 2 years, but some did not. You have also concluded that long COVID is a chronic disease. Why?

We’ve been in this journey a little bit more than three and a half years. Some patients do experience some recovery. But that’s not the norm. Most people do not really fully recover. The health trajectory for people with long COVID is really very heterogeneous. There is no one-size-fits-all. There’s really no one line that I could give you that could cover all your patients. But it is very, very, very clear that a bunch of them experienced long COVID for sure; that’s really happening.

It happened in the pre-Delta era and in the Delta era, and with Omicron subvariants, even now. There are people who think, “This is a nothing-burger anymore,” or “It’s not an issue anymore.” It’s still happening with the current variants. Vaccines do reduce risk for long COVID, but do not completely eliminate the risk for long COVID.

You work with patients with long COVID in the clinic and also analyze data from thousands more. If long COVID does not go away, what should doctors look for in everyday practice that will help them recognize and help patients with long COVID?

Long COVID is not uncommon. We see it in the clinic in large numbers. Whatever clinic you’re running – if you’re running a cardiology clinic, or a nephrology clinic, or diabetes, or primary care – probably some of your people have it. You may not know about it. They may not tell you about it. You may not recognize it.

Not all long COVID is the same, and that’s really what makes it complex and makes it really hard to deal with in the clinic. But that’s the reality that we’re all dealing with. And it’s multisystemic; it’s not like it affects the heart only, the brain only, or the autonomic nervous system only. It does not behave in the same way in different individuals – they may have different manifestations, various health trajectories, and different outcomes. It’s important for doctors to get up to speed on long COVID as a multisystem illness.

Management at this point is really managing the symptoms. We don’t have a treatment for it; we don’t have a cure for it.

Some patients experience what you’ve described as partial recovery. What does that look like?

Some individuals do experience some recovery over time, but for most individuals, the recovery is long and arduous. Long COVID can last with them for many years. Some people may come back to the clinic and say, “I’m doing better,” but if you really flesh it out and dig deeper, they didn’t do better; they adjusted to a new baseline. They used to walk the dog three to four blocks, and now they walk the dog only half a block. They used to do an activity with their partner every Saturday or Sunday, and now they do half of that.

If you’re a physician, a primary care provider, or any other provider who is dealing with a patient with long COVID, know that this is really happening. It can happen even in vaccinated individuals. The presentation is heterogeneous. Some people may present to you with and say. “Well, before I had COVID I was mentally sharp and now having I’m having difficulty with memory, etc.” It can sometimes present as fatigue or postexertional malaise.

In some instances, it can present as sleep problems. It can present as what we call postural orthostatic tachycardia syndrome (POTS). Those people get a significant increase in heart rate with postural changes.

What the most important thing we can we learn from the emergence of long COVID?

This whole thing taught us that infections can cause chronic disease. That’s really the No. 1 lesson that I take from this pandemic – that infections can cause chronic disease.

Looking at only acute illness from COVID is really only looking at the tip of the iceberg. Beneath that tip of the iceberg lies this hidden toll of disease that we don’t really talk about that much.

This pandemic shone a very, very good light on the idea that there is really an intimate connection between infections and chronic disease. It was really hardwired into our medical training as doctors that most infections, when people get over the hump of the acute phase of the disease, it’s all behind them. I think long COVID has humbled us in many, many ways, but chief among those is the realization – the stark realization – that infections can cause chronic disease.

That’s really going back to your [first] question: What does it mean that some people are not recovering? They actually have chronic illness. I’m hoping that we will find a treatment, that we’ll start finding things that would help them get back to baseline. But at this point in time, what we’re dealing with is people with chronic illness or chronic disease that may continue to affect them for many years to come in the absence of a treatment or a cure.

A version of this article first appeared on Medscape.com.

Physicians in 2024 can expect a 3.4% drop in the conversion factor that determines their base Medicare pay, according to federal officials, but they also will receive more money for primary care and treating complex conditions.

The Centers for Medicare & Medicaid Services on Nov. 2 released its 2024 final physician fee schedule, triggering renewed concerns from doctors’ groups, who protested CMS’ cuts when they were first previewed earlier in 2023.

The 2024 conversion factor, or base rate for clinician pay, will be $32.74, a decrease of $1.15, or 3.4%, from 2023’s level. The pay cuts come as costs of providing health care are expected to rise as much as 4.6% in 2024, the American Medical Association said.

The new rule follows a 2% payment reduction in 2023, AMA president Jesse M. Ehrenfeld, MD, MPH, said in a statement.

“This is a recipe for financial instability,” Dr. Ehrenfeld said. “Patients and physicians will wonder why such thin gruel is being served.”

The AMA is among the many physician groups pressing Congress to change its approach to paying clinicians and consider inflation rates in determining future payments.

Medicare already includes automatic inflation adjusters in other payment rules, such as the ones for care provided in hospitals. But Congress in 2015 eliminated this feature for the physician fee schedule when it passed the Medicare Access and CHIP Reauthorization Act.

A pending House bill, the bipartisan Strengthening Medicare for Patients and Providers Act (H.R.2474), would return to permanently including a broader inflation adjuster in the Medicare physician fee schedule.

“This long-overdue change would not only help provide greater stability within the Medicare payment system, but it would also help physicians’ practices – many of whom operate as small business owners – more effectively navigate the ever-changing economic factors that impact their practices, including rising medical costs, workforce and labor challenges, administrative burdens, office rental prices and more,” Larry Bucshon, MD (R-Ind.), Ami Bera, MD (D-Calif.), Raul Ruiz, MD (D-Calif.), and Mariannette Miller-Meeks, MD (R-Iowa), wrote in an opinion article in the newspaper The Hill.

Major changes to determining Medicare physician pay remain unlikely in 2023. Still, Congress has softened or blocked slated cuts in physician pay in recent years, passing temporary “doc fixes” as add-ons to spending packages.
 

E/M add-on payment

“We’re encouraged to see that CMS listened to our concerns and extended telehealth flexibilities as well as implemented the G2211 code, which will help Medicare beneficiaries and their physicians better manage complex and chronic rheumatic diseases,” said Douglas White, MD, PhD, president of the ACR.

A version of this article first appeared on Medscape.com.

Physicians in 2024 can expect a 3.4% drop in the conversion factor that determines their base Medicare pay, according to federal officials, but they also will receive more money for primary care and treating complex conditions.

The Centers for Medicare & Medicaid Services on Nov. 2 released its 2024 final physician fee schedule, triggering renewed concerns from doctors’ groups, who protested CMS’ cuts when they were first previewed earlier in 2023.

The 2024 conversion factor, or base rate for clinician pay, will be $32.74, a decrease of $1.15, or 3.4%, from 2023’s level. The pay cuts come as costs of providing health care are expected to rise as much as 4.6% in 2024, the American Medical Association said.

The new rule follows a 2% payment reduction in 2023, AMA president Jesse M. Ehrenfeld, MD, MPH, said in a statement.

“This is a recipe for financial instability,” Dr. Ehrenfeld said. “Patients and physicians will wonder why such thin gruel is being served.”

The AMA is among the many physician groups pressing Congress to change its approach to paying clinicians and consider inflation rates in determining future payments.

Medicare already includes automatic inflation adjusters in other payment rules, such as the ones for care provided in hospitals. But Congress in 2015 eliminated this feature for the physician fee schedule when it passed the Medicare Access and CHIP Reauthorization Act.

A pending House bill, the bipartisan Strengthening Medicare for Patients and Providers Act (H.R.2474), would return to permanently including a broader inflation adjuster in the Medicare physician fee schedule.

“This long-overdue change would not only help provide greater stability within the Medicare payment system, but it would also help physicians’ practices – many of whom operate as small business owners – more effectively navigate the ever-changing economic factors that impact their practices, including rising medical costs, workforce and labor challenges, administrative burdens, office rental prices and more,” Larry Bucshon, MD (R-Ind.), Ami Bera, MD (D-Calif.), Raul Ruiz, MD (D-Calif.), and Mariannette Miller-Meeks, MD (R-Iowa), wrote in an opinion article in the newspaper The Hill.

Major changes to determining Medicare physician pay remain unlikely in 2023. Still, Congress has softened or blocked slated cuts in physician pay in recent years, passing temporary “doc fixes” as add-ons to spending packages.
 

E/M add-on payment

“We’re encouraged to see that CMS listened to our concerns and extended telehealth flexibilities as well as implemented the G2211 code, which will help Medicare beneficiaries and their physicians better manage complex and chronic rheumatic diseases,” said Douglas White, MD, PhD, president of the ACR.

A version of this article first appeared on Medscape.com.

Physicians in 2024 can expect a 3.4% drop in the conversion factor that determines their base Medicare pay, according to federal officials, but they also will receive more money for primary care and treating complex conditions.

The Centers for Medicare & Medicaid Services on Nov. 2 released its 2024 final physician fee schedule, triggering renewed concerns from doctors’ groups, who protested CMS’ cuts when they were first previewed earlier in 2023.

The 2024 conversion factor, or base rate for clinician pay, will be $32.74, a decrease of $1.15, or 3.4%, from 2023’s level. The pay cuts come as costs of providing health care are expected to rise as much as 4.6% in 2024, the American Medical Association said.

The new rule follows a 2% payment reduction in 2023, AMA president Jesse M. Ehrenfeld, MD, MPH, said in a statement.

“This is a recipe for financial instability,” Dr. Ehrenfeld said. “Patients and physicians will wonder why such thin gruel is being served.”

The AMA is among the many physician groups pressing Congress to change its approach to paying clinicians and consider inflation rates in determining future payments.

Medicare already includes automatic inflation adjusters in other payment rules, such as the ones for care provided in hospitals. But Congress in 2015 eliminated this feature for the physician fee schedule when it passed the Medicare Access and CHIP Reauthorization Act.

A pending House bill, the bipartisan Strengthening Medicare for Patients and Providers Act (H.R.2474), would return to permanently including a broader inflation adjuster in the Medicare physician fee schedule.

“This long-overdue change would not only help provide greater stability within the Medicare payment system, but it would also help physicians’ practices – many of whom operate as small business owners – more effectively navigate the ever-changing economic factors that impact their practices, including rising medical costs, workforce and labor challenges, administrative burdens, office rental prices and more,” Larry Bucshon, MD (R-Ind.), Ami Bera, MD (D-Calif.), Raul Ruiz, MD (D-Calif.), and Mariannette Miller-Meeks, MD (R-Iowa), wrote in an opinion article in the newspaper The Hill.

Major changes to determining Medicare physician pay remain unlikely in 2023. Still, Congress has softened or blocked slated cuts in physician pay in recent years, passing temporary “doc fixes” as add-ons to spending packages.
 

E/M add-on payment

“We’re encouraged to see that CMS listened to our concerns and extended telehealth flexibilities as well as implemented the G2211 code, which will help Medicare beneficiaries and their physicians better manage complex and chronic rheumatic diseases,” said Douglas White, MD, PhD, president of the ACR.

A version of this article first appeared on Medscape.com.