Rheumatology News

As I prepared to write my monthly column, I came across the statistic that 23% of physicians and 40% of nurses plan to leave their practices in the next 2 years.¹

Interestingly, the group that seems to be least impacted by this was health care administrators (with 12% of them planning on leaving their jobs).

I couldn’t stop thinking about these percentages.

I am reminded every day of the commitment and excellence of my colleagues in the health care field, and I do not want to lose them. I am hoping the following information and my thoughts on this topic will be helpful for those thinking about leaving health care.
 

Surgeon general’s burnout report

The surgeon general recently released a report on addressing health care worker burnout.² It includes several very interesting and appropriate observations. I will summarize the most important ones here:

1. Our health depends on the well-being of our health workforce.

2. Direct harm to health care workers can lead to anxiety, depression, insomnia, and interpersonal and relationship struggles.

3. Health care workers experience exhaustion from providing overwhelming care and empathy.

4. Health care workers spend less time with patients and too much time with EHRs.

5. There are health workforce shortages.

The report is comprehensive, and everything in it is correct. The real issue is how does it go from being a report to true actionable items that we as health care professionals benefit from? I think in regards to exhaustion from overwhelming care responsibilities, and empathy fatigue, we need better boundaries.

Those who go into medicine, and especially those who go into primary care, always put the patients’ needs first. When operating in a broken system, it stays broken when individuals cover for the deficiencies in the system. Adding four extra patients every day because there is no one to refer them to with availability is injurious to the health care provider, and those providers who accept these additional patients will eventually be part of the 23% who want to leave their jobs. It feels awful to say no, but until the system stops accommodating there will not be substantial change.
 

The empathy drain

One of the unreported stresses of open access for patients through EHR communications is the empathy drain on physicians. When I see a patient in clinic with chronic symptoms or issues, I spend important time making sure we have a plan and an agreed upon time frame.

With the EHR, patients frequently send multiple messages for the same symptoms between visits. It is okay to redirect the patient and share that these issues will be discussed at length at appointments. My reasoning on this is that I think it is better for me to better care for myself and stay as the doctor for my patients, than always say yes to limitless needs and soon be looking for the off ramp.

The following statistic in the surgeon general’s report really hit home. For every hour of direct patient care, physicians currently spend 2 hours on the EHR system. Most practices allow 10%-20% of time for catch up, where with statistics like this it should be 50%. This concept is fully lost on administrators, or ignored.

It is only when we refuse to continue to accept and follow a broken system that it will change. A minority of internal medicine and family doctors (4.5% in 2018) practice in direct primary care models, where these issues are addressed. Unfortunately, this model as it is currently available is not an option for lower income patients.

A major theme in the surgeon general’s report was that administrative burdens need to be reduced by 75% by 2025. When I look at the report, I see the suggestions, I just don’t see how it will be achieved. Despite almost all clinics moving to the EHR, paperwork in the form of faxes and forms has increased.

A sweeping reform would be needed to eliminate daily faxes from PT offices, visiting nurse services, prior authorization, patients reminders from insurance companies, and disability forms from patients. I am glad that there is acknowledgment of the problem, but this change will take more than 3 years.
 

Takeaways

So what do we do?

Be good to yourself, and your colleagues. The pandemic has isolated us, which accelerates burnout.

Reach out to people you care about.

We are all feeling this. Set boundaries that allow you to care for yourself, and accept that you are doing your best, even if you can’t meet the needs of all your patients all the time.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Sinsky CA et al. Covid-related stress and work intentions in a sample of US health care workers. Mayo Clin Proc Innov Qual Outcomes. 2021 Dec;5(6):1165-73.

2. Addressing health worker burnout. The U.S. Surgeon General’s advisory on building a thriving health workforce.

As I prepared to write my monthly column, I came across the statistic that 23% of physicians and 40% of nurses plan to leave their practices in the next 2 years.¹

Interestingly, the group that seems to be least impacted by this was health care administrators (with 12% of them planning on leaving their jobs).

I couldn’t stop thinking about these percentages.

I am reminded every day of the commitment and excellence of my colleagues in the health care field, and I do not want to lose them. I am hoping the following information and my thoughts on this topic will be helpful for those thinking about leaving health care.
 

Surgeon general’s burnout report

The surgeon general recently released a report on addressing health care worker burnout.² It includes several very interesting and appropriate observations. I will summarize the most important ones here:

1. Our health depends on the well-being of our health workforce.

2. Direct harm to health care workers can lead to anxiety, depression, insomnia, and interpersonal and relationship struggles.

3. Health care workers experience exhaustion from providing overwhelming care and empathy.

4. Health care workers spend less time with patients and too much time with EHRs.

5. There are health workforce shortages.

The report is comprehensive, and everything in it is correct. The real issue is how does it go from being a report to true actionable items that we as health care professionals benefit from? I think in regards to exhaustion from overwhelming care responsibilities, and empathy fatigue, we need better boundaries.

Those who go into medicine, and especially those who go into primary care, always put the patients’ needs first. When operating in a broken system, it stays broken when individuals cover for the deficiencies in the system. Adding four extra patients every day because there is no one to refer them to with availability is injurious to the health care provider, and those providers who accept these additional patients will eventually be part of the 23% who want to leave their jobs. It feels awful to say no, but until the system stops accommodating there will not be substantial change.
 

The empathy drain

One of the unreported stresses of open access for patients through EHR communications is the empathy drain on physicians. When I see a patient in clinic with chronic symptoms or issues, I spend important time making sure we have a plan and an agreed upon time frame.

With the EHR, patients frequently send multiple messages for the same symptoms between visits. It is okay to redirect the patient and share that these issues will be discussed at length at appointments. My reasoning on this is that I think it is better for me to better care for myself and stay as the doctor for my patients, than always say yes to limitless needs and soon be looking for the off ramp.

The following statistic in the surgeon general’s report really hit home. For every hour of direct patient care, physicians currently spend 2 hours on the EHR system. Most practices allow 10%-20% of time for catch up, where with statistics like this it should be 50%. This concept is fully lost on administrators, or ignored.

It is only when we refuse to continue to accept and follow a broken system that it will change. A minority of internal medicine and family doctors (4.5% in 2018) practice in direct primary care models, where these issues are addressed. Unfortunately, this model as it is currently available is not an option for lower income patients.

A major theme in the surgeon general’s report was that administrative burdens need to be reduced by 75% by 2025. When I look at the report, I see the suggestions, I just don’t see how it will be achieved. Despite almost all clinics moving to the EHR, paperwork in the form of faxes and forms has increased.

A sweeping reform would be needed to eliminate daily faxes from PT offices, visiting nurse services, prior authorization, patients reminders from insurance companies, and disability forms from patients. I am glad that there is acknowledgment of the problem, but this change will take more than 3 years.
 

Takeaways

So what do we do?

Be good to yourself, and your colleagues. The pandemic has isolated us, which accelerates burnout.

Reach out to people you care about.

We are all feeling this. Set boundaries that allow you to care for yourself, and accept that you are doing your best, even if you can’t meet the needs of all your patients all the time.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Sinsky CA et al. Covid-related stress and work intentions in a sample of US health care workers. Mayo Clin Proc Innov Qual Outcomes. 2021 Dec;5(6):1165-73.

2. Addressing health worker burnout. The U.S. Surgeon General’s advisory on building a thriving health workforce.

As I prepared to write my monthly column, I came across the statistic that 23% of physicians and 40% of nurses plan to leave their practices in the next 2 years.¹

Interestingly, the group that seems to be least impacted by this was health care administrators (with 12% of them planning on leaving their jobs).

I couldn’t stop thinking about these percentages.

I am reminded every day of the commitment and excellence of my colleagues in the health care field, and I do not want to lose them. I am hoping the following information and my thoughts on this topic will be helpful for those thinking about leaving health care.
 

Surgeon general’s burnout report

The surgeon general recently released a report on addressing health care worker burnout.² It includes several very interesting and appropriate observations. I will summarize the most important ones here:

1. Our health depends on the well-being of our health workforce.

2. Direct harm to health care workers can lead to anxiety, depression, insomnia, and interpersonal and relationship struggles.

3. Health care workers experience exhaustion from providing overwhelming care and empathy.

4. Health care workers spend less time with patients and too much time with EHRs.

5. There are health workforce shortages.

The report is comprehensive, and everything in it is correct. The real issue is how does it go from being a report to true actionable items that we as health care professionals benefit from? I think in regards to exhaustion from overwhelming care responsibilities, and empathy fatigue, we need better boundaries.

Those who go into medicine, and especially those who go into primary care, always put the patients’ needs first. When operating in a broken system, it stays broken when individuals cover for the deficiencies in the system. Adding four extra patients every day because there is no one to refer them to with availability is injurious to the health care provider, and those providers who accept these additional patients will eventually be part of the 23% who want to leave their jobs. It feels awful to say no, but until the system stops accommodating there will not be substantial change.
 

The empathy drain

One of the unreported stresses of open access for patients through EHR communications is the empathy drain on physicians. When I see a patient in clinic with chronic symptoms or issues, I spend important time making sure we have a plan and an agreed upon time frame.

With the EHR, patients frequently send multiple messages for the same symptoms between visits. It is okay to redirect the patient and share that these issues will be discussed at length at appointments. My reasoning on this is that I think it is better for me to better care for myself and stay as the doctor for my patients, than always say yes to limitless needs and soon be looking for the off ramp.

The following statistic in the surgeon general’s report really hit home. For every hour of direct patient care, physicians currently spend 2 hours on the EHR system. Most practices allow 10%-20% of time for catch up, where with statistics like this it should be 50%. This concept is fully lost on administrators, or ignored.

It is only when we refuse to continue to accept and follow a broken system that it will change. A minority of internal medicine and family doctors (4.5% in 2018) practice in direct primary care models, where these issues are addressed. Unfortunately, this model as it is currently available is not an option for lower income patients.

A major theme in the surgeon general’s report was that administrative burdens need to be reduced by 75% by 2025. When I look at the report, I see the suggestions, I just don’t see how it will be achieved. Despite almost all clinics moving to the EHR, paperwork in the form of faxes and forms has increased.

A sweeping reform would be needed to eliminate daily faxes from PT offices, visiting nurse services, prior authorization, patients reminders from insurance companies, and disability forms from patients. I am glad that there is acknowledgment of the problem, but this change will take more than 3 years.
 

Takeaways

So what do we do?

Be good to yourself, and your colleagues. The pandemic has isolated us, which accelerates burnout.

Reach out to people you care about.

We are all feeling this. Set boundaries that allow you to care for yourself, and accept that you are doing your best, even if you can’t meet the needs of all your patients all the time.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. Sinsky CA et al. Covid-related stress and work intentions in a sample of US health care workers. Mayo Clin Proc Innov Qual Outcomes. 2021 Dec;5(6):1165-73.

2. Addressing health worker burnout. The U.S. Surgeon General’s advisory on building a thriving health workforce.

There is evidence that gout and heart disease are mechanistically linked by inflammation and patients with gout are at elevated risk for cardiovascular disease (CVD). But do gout flares, on their own, affect short-term risk for CV events? A new analysis based on records from British medical practices suggests that might be the case.

Risk for myocardial infarction or stroke climbed in the weeks after individual gout flare-ups in the study’s more than 60,000 patients with a recent gout diagnosis. The jump in risk, significant but small in absolute terms, held for about 4 months in the case-control study before going away.

A sensitivity analysis that excluded patients who already had CVD when their gout was diagnosed yielded similar results.

The observational study isn’t able to show that gout flares themselves transiently raise the risk for MI or stroke, but it’s enough to send a cautionary message to physicians who care for patients with gout, rheumatologist Abhishek Abhishek, PhD, Nottingham (England) City Hospital, said in an interview.

In such patients who also have conditions like hypertension, diabetes, or dyslipidemia, or a history of heart disease, he said, it’s important “to manage risk factors really aggressively, knowing that when these patients have a gout flare, there’s a temporary increase in risk of a cardiovascular event.”

Managing their absolute CV risk – whether with drug therapy, lifestyle changes, or other interventions – should help limit the transient jump in risk for MI or stroke following a gout flare, proposed Dr. Abhishek, who is senior author on the study published in JAMA, with lead author Edoardo Cipolletta, MD, also from Nottingham City Hospital.

First robust evidence

The case-control study, which involved more than 60,000 patients with a recent gout diagnosis, some who went on to have MI or stroke, looked at rates of such events at different time intervals after gout flares. Those who experienced such events showed a more than 90% increased likelihood of a gout flare-up in the preceding 60 days, a greater than 50% chance of a flare between 60 and 120 days before the event, but no increased likelihood prior to 120 days before the event.

Such a link between gout flares and CV events “has been suspected but never proven,” observed rheumatologist Hyon K. Choi, MD, Harvard Medical School, Boston, who was not associated with the analysis. “This is the first time it has actually been shown in a robust way,” he said in an interview.

The study suggests a “likely causative relationship” between gout flares and CV events, but – as the published report noted – has limitations like any observational study, said Dr. Choi, who also directs the Gout & Crystal Arthropathy Center at Massachusetts General Hospital, Boston. “Hopefully, this can be replicated in other cohorts.”

The analysis controlled for a number of relevant potential confounders, he noted, but couldn’t account for all issues that could argue against gout flares as a direct cause of the MIs and strokes.

Gout attacks are a complex experience with a range of potential indirect effects on CV risk, Dr. Choi observed. They can immobilize patients, possibly raising their risk for thrombotic events, for example. They can be exceptionally painful, which causes stress and can lead to frequent or chronic use of glucocorticoids or NSAIDs, all of which can exacerbate high blood pressure and possibly worsen CV risk.
 

A unique insight

The timing of gout flares relative to acute vascular events hasn’t been fully explored, observed an accompanying editorial. The current study’s “unique insight,” it stated, “is that disease activity from gout was associated with an incremental increase in risk for acute vascular events during the time period immediately following the gout flare.”

Although the study is observational, a “large body of evidence from animal and human research, mechanistic insights, and clinical interventions” support an association between flares and vascular events and “make a causal link eminently reasonable,” stated the editorialists, Jeffrey L. Anderson, MD, and Kirk U. Knowlton, MD, both with Intermountain Medical Center, Salt Lake City, Utah.

The findings, they wrote, “should alert clinicians and patients to the increased cardiovascular risk in the weeks beginning after a gout flare and should focus attention on optimizing preventive measures.” Those can include “lifestyle measures and standard risk-factor control including adherence to diet, statins, anti-inflammatory drugs (e.g., aspirin, colchicine), smoking cessation, diabetic and blood pressure control, and antithrombotic medications as indicated.”

Dr. Choi said the current results argue for more liberal use of colchicine, and for preferring colchicine over other anti-inflammatories, in patients with gout and traditional CV risk factors, given multiple randomized trials supporting the drug’s use in such cases. “If you use colchicine, you are covering their heart disease risk as well as their gout. It’s two birds with one stone.”
 

Nested case-control study

The investigators accessed electronic health records from 96,153 patients with recently diagnosed gout in England from 1997 to 2020; the cohort’s mean age was about 76 years, and 69% of participants were men. They matched 10,475 patients with at least one CV event to 52,099 others who didn’t have such an event by age, sex, and time from gout diagnosis. In each matched set of patients, those not experiencing a CV event were assigned a flare-to-event interval based on their matching with patients who did experience such an event.

Those with CV events, compared with patients without an event, had a greater than 90% increased likelihood of experiencing a gout flare-up in the 60 days preceding the event, a more than 50% greater chance of a flare-up 60-120 days before the CV event, but no increased likelihood more than 120 days before the event.

A self-controlled case series based on the same overall cohort with gout yielded similar results while sidestepping any potential for residual confounding, an inherent concern with any case–control analysis, the report notes. It involved 1,421 patients with one or more gout flare and at least one MI or stroke after the diagnosis of gout.

Among that cohort, the CV-event incidence rate ratio, adjusted for age and season of the year, by time interval after a gout flare, was 1.89 (95% confidence interval, 1.54-2.30) at 0-60 days, 1.64 (95% CI, 1.45-1.86) at 61-120 days, and1.29 (95% CI, 1.02-1.64) at 121-180 days.

Also similar, the report noted, were results of several sensitivity analyses, including one that excluded patients with confirmed CVD before their gout diagnosis; another that left out patients at low to moderate CV risk; and one that considered only gout flares treated with colchicine, corticosteroids, or NSAIDs.

The incremental CV event risks observed after flares in the study were small, which “has implications for both cost effectiveness and clinical relevance,” observed Dr. Anderson and Dr. Knowlton.

“An alternative to universal augmentation of cardiovascular risk prevention with therapies among patients with gout flares,” they wrote, would be “to further stratify risk by defining a group at highest near-term risk.” Such interventions could potentially be guided by markers of CV risk such as, for example, levels of high-sensitivity C-reactive protein or lipoprotein(a), or plaque burden on coronary-artery calcium scans.

Dr. Abhishek, Dr. Cipolletta, and the other authors reported no competing interests. Dr. Choi disclosed research support from Ironwood and Horizon; and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart. Dr. Anderson disclosed receiving grants to his institution from Novartis and Milestone.

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

There is evidence that gout and heart disease are mechanistically linked by inflammation and patients with gout are at elevated risk for cardiovascular disease (CVD). But do gout flares, on their own, affect short-term risk for CV events? A new analysis based on records from British medical practices suggests that might be the case.

Risk for myocardial infarction or stroke climbed in the weeks after individual gout flare-ups in the study’s more than 60,000 patients with a recent gout diagnosis. The jump in risk, significant but small in absolute terms, held for about 4 months in the case-control study before going away.

A sensitivity analysis that excluded patients who already had CVD when their gout was diagnosed yielded similar results.

The observational study isn’t able to show that gout flares themselves transiently raise the risk for MI or stroke, but it’s enough to send a cautionary message to physicians who care for patients with gout, rheumatologist Abhishek Abhishek, PhD, Nottingham (England) City Hospital, said in an interview.

In such patients who also have conditions like hypertension, diabetes, or dyslipidemia, or a history of heart disease, he said, it’s important “to manage risk factors really aggressively, knowing that when these patients have a gout flare, there’s a temporary increase in risk of a cardiovascular event.”

Managing their absolute CV risk – whether with drug therapy, lifestyle changes, or other interventions – should help limit the transient jump in risk for MI or stroke following a gout flare, proposed Dr. Abhishek, who is senior author on the study published in JAMA, with lead author Edoardo Cipolletta, MD, also from Nottingham City Hospital.

First robust evidence

The case-control study, which involved more than 60,000 patients with a recent gout diagnosis, some who went on to have MI or stroke, looked at rates of such events at different time intervals after gout flares. Those who experienced such events showed a more than 90% increased likelihood of a gout flare-up in the preceding 60 days, a greater than 50% chance of a flare between 60 and 120 days before the event, but no increased likelihood prior to 120 days before the event.

Such a link between gout flares and CV events “has been suspected but never proven,” observed rheumatologist Hyon K. Choi, MD, Harvard Medical School, Boston, who was not associated with the analysis. “This is the first time it has actually been shown in a robust way,” he said in an interview.

The study suggests a “likely causative relationship” between gout flares and CV events, but – as the published report noted – has limitations like any observational study, said Dr. Choi, who also directs the Gout & Crystal Arthropathy Center at Massachusetts General Hospital, Boston. “Hopefully, this can be replicated in other cohorts.”

The analysis controlled for a number of relevant potential confounders, he noted, but couldn’t account for all issues that could argue against gout flares as a direct cause of the MIs and strokes.

Gout attacks are a complex experience with a range of potential indirect effects on CV risk, Dr. Choi observed. They can immobilize patients, possibly raising their risk for thrombotic events, for example. They can be exceptionally painful, which causes stress and can lead to frequent or chronic use of glucocorticoids or NSAIDs, all of which can exacerbate high blood pressure and possibly worsen CV risk.
 

A unique insight

The timing of gout flares relative to acute vascular events hasn’t been fully explored, observed an accompanying editorial. The current study’s “unique insight,” it stated, “is that disease activity from gout was associated with an incremental increase in risk for acute vascular events during the time period immediately following the gout flare.”

Although the study is observational, a “large body of evidence from animal and human research, mechanistic insights, and clinical interventions” support an association between flares and vascular events and “make a causal link eminently reasonable,” stated the editorialists, Jeffrey L. Anderson, MD, and Kirk U. Knowlton, MD, both with Intermountain Medical Center, Salt Lake City, Utah.

The findings, they wrote, “should alert clinicians and patients to the increased cardiovascular risk in the weeks beginning after a gout flare and should focus attention on optimizing preventive measures.” Those can include “lifestyle measures and standard risk-factor control including adherence to diet, statins, anti-inflammatory drugs (e.g., aspirin, colchicine), smoking cessation, diabetic and blood pressure control, and antithrombotic medications as indicated.”

Dr. Choi said the current results argue for more liberal use of colchicine, and for preferring colchicine over other anti-inflammatories, in patients with gout and traditional CV risk factors, given multiple randomized trials supporting the drug’s use in such cases. “If you use colchicine, you are covering their heart disease risk as well as their gout. It’s two birds with one stone.”
 

Nested case-control study

The investigators accessed electronic health records from 96,153 patients with recently diagnosed gout in England from 1997 to 2020; the cohort’s mean age was about 76 years, and 69% of participants were men. They matched 10,475 patients with at least one CV event to 52,099 others who didn’t have such an event by age, sex, and time from gout diagnosis. In each matched set of patients, those not experiencing a CV event were assigned a flare-to-event interval based on their matching with patients who did experience such an event.

Those with CV events, compared with patients without an event, had a greater than 90% increased likelihood of experiencing a gout flare-up in the 60 days preceding the event, a more than 50% greater chance of a flare-up 60-120 days before the CV event, but no increased likelihood more than 120 days before the event.

A self-controlled case series based on the same overall cohort with gout yielded similar results while sidestepping any potential for residual confounding, an inherent concern with any case–control analysis, the report notes. It involved 1,421 patients with one or more gout flare and at least one MI or stroke after the diagnosis of gout.

Among that cohort, the CV-event incidence rate ratio, adjusted for age and season of the year, by time interval after a gout flare, was 1.89 (95% confidence interval, 1.54-2.30) at 0-60 days, 1.64 (95% CI, 1.45-1.86) at 61-120 days, and1.29 (95% CI, 1.02-1.64) at 121-180 days.

Also similar, the report noted, were results of several sensitivity analyses, including one that excluded patients with confirmed CVD before their gout diagnosis; another that left out patients at low to moderate CV risk; and one that considered only gout flares treated with colchicine, corticosteroids, or NSAIDs.

The incremental CV event risks observed after flares in the study were small, which “has implications for both cost effectiveness and clinical relevance,” observed Dr. Anderson and Dr. Knowlton.

“An alternative to universal augmentation of cardiovascular risk prevention with therapies among patients with gout flares,” they wrote, would be “to further stratify risk by defining a group at highest near-term risk.” Such interventions could potentially be guided by markers of CV risk such as, for example, levels of high-sensitivity C-reactive protein or lipoprotein(a), or plaque burden on coronary-artery calcium scans.

Dr. Abhishek, Dr. Cipolletta, and the other authors reported no competing interests. Dr. Choi disclosed research support from Ironwood and Horizon; and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart. Dr. Anderson disclosed receiving grants to his institution from Novartis and Milestone.

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

There is evidence that gout and heart disease are mechanistically linked by inflammation and patients with gout are at elevated risk for cardiovascular disease (CVD). But do gout flares, on their own, affect short-term risk for CV events? A new analysis based on records from British medical practices suggests that might be the case.

Risk for myocardial infarction or stroke climbed in the weeks after individual gout flare-ups in the study’s more than 60,000 patients with a recent gout diagnosis. The jump in risk, significant but small in absolute terms, held for about 4 months in the case-control study before going away.

A sensitivity analysis that excluded patients who already had CVD when their gout was diagnosed yielded similar results.

The observational study isn’t able to show that gout flares themselves transiently raise the risk for MI or stroke, but it’s enough to send a cautionary message to physicians who care for patients with gout, rheumatologist Abhishek Abhishek, PhD, Nottingham (England) City Hospital, said in an interview.

In such patients who also have conditions like hypertension, diabetes, or dyslipidemia, or a history of heart disease, he said, it’s important “to manage risk factors really aggressively, knowing that when these patients have a gout flare, there’s a temporary increase in risk of a cardiovascular event.”

Managing their absolute CV risk – whether with drug therapy, lifestyle changes, or other interventions – should help limit the transient jump in risk for MI or stroke following a gout flare, proposed Dr. Abhishek, who is senior author on the study published in JAMA, with lead author Edoardo Cipolletta, MD, also from Nottingham City Hospital.

First robust evidence

The case-control study, which involved more than 60,000 patients with a recent gout diagnosis, some who went on to have MI or stroke, looked at rates of such events at different time intervals after gout flares. Those who experienced such events showed a more than 90% increased likelihood of a gout flare-up in the preceding 60 days, a greater than 50% chance of a flare between 60 and 120 days before the event, but no increased likelihood prior to 120 days before the event.

Such a link between gout flares and CV events “has been suspected but never proven,” observed rheumatologist Hyon K. Choi, MD, Harvard Medical School, Boston, who was not associated with the analysis. “This is the first time it has actually been shown in a robust way,” he said in an interview.

The study suggests a “likely causative relationship” between gout flares and CV events, but – as the published report noted – has limitations like any observational study, said Dr. Choi, who also directs the Gout & Crystal Arthropathy Center at Massachusetts General Hospital, Boston. “Hopefully, this can be replicated in other cohorts.”

The analysis controlled for a number of relevant potential confounders, he noted, but couldn’t account for all issues that could argue against gout flares as a direct cause of the MIs and strokes.

Gout attacks are a complex experience with a range of potential indirect effects on CV risk, Dr. Choi observed. They can immobilize patients, possibly raising their risk for thrombotic events, for example. They can be exceptionally painful, which causes stress and can lead to frequent or chronic use of glucocorticoids or NSAIDs, all of which can exacerbate high blood pressure and possibly worsen CV risk.
 

A unique insight

The timing of gout flares relative to acute vascular events hasn’t been fully explored, observed an accompanying editorial. The current study’s “unique insight,” it stated, “is that disease activity from gout was associated with an incremental increase in risk for acute vascular events during the time period immediately following the gout flare.”

Although the study is observational, a “large body of evidence from animal and human research, mechanistic insights, and clinical interventions” support an association between flares and vascular events and “make a causal link eminently reasonable,” stated the editorialists, Jeffrey L. Anderson, MD, and Kirk U. Knowlton, MD, both with Intermountain Medical Center, Salt Lake City, Utah.

The findings, they wrote, “should alert clinicians and patients to the increased cardiovascular risk in the weeks beginning after a gout flare and should focus attention on optimizing preventive measures.” Those can include “lifestyle measures and standard risk-factor control including adherence to diet, statins, anti-inflammatory drugs (e.g., aspirin, colchicine), smoking cessation, diabetic and blood pressure control, and antithrombotic medications as indicated.”

Dr. Choi said the current results argue for more liberal use of colchicine, and for preferring colchicine over other anti-inflammatories, in patients with gout and traditional CV risk factors, given multiple randomized trials supporting the drug’s use in such cases. “If you use colchicine, you are covering their heart disease risk as well as their gout. It’s two birds with one stone.”
 

Nested case-control study

The investigators accessed electronic health records from 96,153 patients with recently diagnosed gout in England from 1997 to 2020; the cohort’s mean age was about 76 years, and 69% of participants were men. They matched 10,475 patients with at least one CV event to 52,099 others who didn’t have such an event by age, sex, and time from gout diagnosis. In each matched set of patients, those not experiencing a CV event were assigned a flare-to-event interval based on their matching with patients who did experience such an event.

Those with CV events, compared with patients without an event, had a greater than 90% increased likelihood of experiencing a gout flare-up in the 60 days preceding the event, a more than 50% greater chance of a flare-up 60-120 days before the CV event, but no increased likelihood more than 120 days before the event.

A self-controlled case series based on the same overall cohort with gout yielded similar results while sidestepping any potential for residual confounding, an inherent concern with any case–control analysis, the report notes. It involved 1,421 patients with one or more gout flare and at least one MI or stroke after the diagnosis of gout.

Among that cohort, the CV-event incidence rate ratio, adjusted for age and season of the year, by time interval after a gout flare, was 1.89 (95% confidence interval, 1.54-2.30) at 0-60 days, 1.64 (95% CI, 1.45-1.86) at 61-120 days, and1.29 (95% CI, 1.02-1.64) at 121-180 days.

Also similar, the report noted, were results of several sensitivity analyses, including one that excluded patients with confirmed CVD before their gout diagnosis; another that left out patients at low to moderate CV risk; and one that considered only gout flares treated with colchicine, corticosteroids, or NSAIDs.

The incremental CV event risks observed after flares in the study were small, which “has implications for both cost effectiveness and clinical relevance,” observed Dr. Anderson and Dr. Knowlton.

“An alternative to universal augmentation of cardiovascular risk prevention with therapies among patients with gout flares,” they wrote, would be “to further stratify risk by defining a group at highest near-term risk.” Such interventions could potentially be guided by markers of CV risk such as, for example, levels of high-sensitivity C-reactive protein or lipoprotein(a), or plaque burden on coronary-artery calcium scans.

Dr. Abhishek, Dr. Cipolletta, and the other authors reported no competing interests. Dr. Choi disclosed research support from Ironwood and Horizon; and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart. Dr. Anderson disclosed receiving grants to his institution from Novartis and Milestone.

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

The Food and Drug Administration has approved the dual interleukin-12 and IL-23 inhibitor ustekinumab (Stelara) for the treatment of juvenile psoriatic arthritis (jPsA) in patients aged 6 years and older, according to an Aug. 1 announcement from its manufacturer, Janssen.

The approval makes jPsA the sixth approved indication for ustekinumab, which include active psoriatic arthritis in adults, moderate to severe plaque psoriasis in both adults and children aged 6 years or older who are candidates for phototherapy or systemic therapy, moderately to severely active Crohn’s disease in adults, and moderately to severely active ulcerative colitis in adults.

In addition, ustekinumab is now the second biologic to be approved for jPsA, following the agency’s December 2021 approval of secukinumab (Cosentyx) to treat jPsA in children and adolescents aged 2 years and older as well as enthesitis-related arthritis in children and adolescents aged 4 years and older.

In pediatric patients, ustekinumab is administered as a subcutaneous injection dosed four times per year after two starter doses.

Ustekinumab’s approval is based on “an extrapolation of the established data and existing safety profile” of ustekinumab in multiple phase 3 studies in adult and pediatric patients with moderate to severe plaque psoriasis and adult patients with active PsA, according to Janssen.

“With the limited availability of pediatric patients for clinical trial inclusion, researchers can extrapolate data from trials with adults to determine the potential efficacy and tolerability of a treatment for a pediatric population,” according to the October 2021 announcement from the company that the Biologics License Application had been submitted to the FDA.

Juvenile arthritis occurs in an estimated 20-45 children per 100,000 in the United States, with about 5% of those children having jPsA, according to the National Psoriasis Foundation.

The prescribing information for ustekinumab includes specific warnings and areas of concern. The drug should not be administered to individuals with known hypersensitivity to ustekinumab. The drug may lower the ability of the immune system to fight infections and may increase risk of infections, sometimes serious, and a test for tuberculosis infection should be given before administration.

Patients taking ustekinumab should not be given a live vaccine, and their doctors should be informed if anyone in their household needs a live vaccine. They also should not receive the BCG vaccine during the 1 year before receiving the drug or 1 year after they stop taking it, according to Johnson & Johnson.

The most common adverse effects include nasal congestion, sore throat, runny nose, upper respiratory infections, fever, headache, tiredness, itching, nausea and vomiting, redness at the injection site, vaginal yeast infections, urinary tract infections, sinus infection, bronchitis, diarrhea, stomach pain, and joint pain.

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

The Food and Drug Administration has approved the dual interleukin-12 and IL-23 inhibitor ustekinumab (Stelara) for the treatment of juvenile psoriatic arthritis (jPsA) in patients aged 6 years and older, according to an Aug. 1 announcement from its manufacturer, Janssen.

The approval makes jPsA the sixth approved indication for ustekinumab, which include active psoriatic arthritis in adults, moderate to severe plaque psoriasis in both adults and children aged 6 years or older who are candidates for phototherapy or systemic therapy, moderately to severely active Crohn’s disease in adults, and moderately to severely active ulcerative colitis in adults.

In addition, ustekinumab is now the second biologic to be approved for jPsA, following the agency’s December 2021 approval of secukinumab (Cosentyx) to treat jPsA in children and adolescents aged 2 years and older as well as enthesitis-related arthritis in children and adolescents aged 4 years and older.

In pediatric patients, ustekinumab is administered as a subcutaneous injection dosed four times per year after two starter doses.

Ustekinumab’s approval is based on “an extrapolation of the established data and existing safety profile” of ustekinumab in multiple phase 3 studies in adult and pediatric patients with moderate to severe plaque psoriasis and adult patients with active PsA, according to Janssen.

“With the limited availability of pediatric patients for clinical trial inclusion, researchers can extrapolate data from trials with adults to determine the potential efficacy and tolerability of a treatment for a pediatric population,” according to the October 2021 announcement from the company that the Biologics License Application had been submitted to the FDA.

Juvenile arthritis occurs in an estimated 20-45 children per 100,000 in the United States, with about 5% of those children having jPsA, according to the National Psoriasis Foundation.

The prescribing information for ustekinumab includes specific warnings and areas of concern. The drug should not be administered to individuals with known hypersensitivity to ustekinumab. The drug may lower the ability of the immune system to fight infections and may increase risk of infections, sometimes serious, and a test for tuberculosis infection should be given before administration.

Patients taking ustekinumab should not be given a live vaccine, and their doctors should be informed if anyone in their household needs a live vaccine. They also should not receive the BCG vaccine during the 1 year before receiving the drug or 1 year after they stop taking it, according to Johnson & Johnson.

The most common adverse effects include nasal congestion, sore throat, runny nose, upper respiratory infections, fever, headache, tiredness, itching, nausea and vomiting, redness at the injection site, vaginal yeast infections, urinary tract infections, sinus infection, bronchitis, diarrhea, stomach pain, and joint pain.

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

The Food and Drug Administration has approved the dual interleukin-12 and IL-23 inhibitor ustekinumab (Stelara) for the treatment of juvenile psoriatic arthritis (jPsA) in patients aged 6 years and older, according to an Aug. 1 announcement from its manufacturer, Janssen.

The approval makes jPsA the sixth approved indication for ustekinumab, which include active psoriatic arthritis in adults, moderate to severe plaque psoriasis in both adults and children aged 6 years or older who are candidates for phototherapy or systemic therapy, moderately to severely active Crohn’s disease in adults, and moderately to severely active ulcerative colitis in adults.

In addition, ustekinumab is now the second biologic to be approved for jPsA, following the agency’s December 2021 approval of secukinumab (Cosentyx) to treat jPsA in children and adolescents aged 2 years and older as well as enthesitis-related arthritis in children and adolescents aged 4 years and older.

In pediatric patients, ustekinumab is administered as a subcutaneous injection dosed four times per year after two starter doses.

Ustekinumab’s approval is based on “an extrapolation of the established data and existing safety profile” of ustekinumab in multiple phase 3 studies in adult and pediatric patients with moderate to severe plaque psoriasis and adult patients with active PsA, according to Janssen.

“With the limited availability of pediatric patients for clinical trial inclusion, researchers can extrapolate data from trials with adults to determine the potential efficacy and tolerability of a treatment for a pediatric population,” according to the October 2021 announcement from the company that the Biologics License Application had been submitted to the FDA.

Juvenile arthritis occurs in an estimated 20-45 children per 100,000 in the United States, with about 5% of those children having jPsA, according to the National Psoriasis Foundation.

The prescribing information for ustekinumab includes specific warnings and areas of concern. The drug should not be administered to individuals with known hypersensitivity to ustekinumab. The drug may lower the ability of the immune system to fight infections and may increase risk of infections, sometimes serious, and a test for tuberculosis infection should be given before administration.

Patients taking ustekinumab should not be given a live vaccine, and their doctors should be informed if anyone in their household needs a live vaccine. They also should not receive the BCG vaccine during the 1 year before receiving the drug or 1 year after they stop taking it, according to Johnson & Johnson.

The most common adverse effects include nasal congestion, sore throat, runny nose, upper respiratory infections, fever, headache, tiredness, itching, nausea and vomiting, redness at the injection site, vaginal yeast infections, urinary tract infections, sinus infection, bronchitis, diarrhea, stomach pain, and joint pain.

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

Skin symptoms, like systemic symptoms, differ by COVID-19 variant, according to a large retrospective study that compared clinical data from more than 300,000 participants in the United Kingdom during the Omicron and Delta waves.

Among the key findings, the study shows that skin involvement during the Omicron wave was less frequent than during the Delta wave (11.4% vs. 17.6%), skin symptoms generally resolved more quickly, and that the risk for skin symptoms was similar whether patients had or had not been vaccinated, according to a team led by Alessia Visconti, PhD, a research fellow in the department of twin research and genetic epidemiology, King’s College, London.

These data are consistent with the experience of those dermatologists who have been following this area closely, according to Esther Freeman, MD, PhD, associate professor of dermatology at Harvard Medical School and director of MGH Global Health Dermatology at Massachusetts General Hospital, both in Boston.

“Anecdotally, we thought we were seeing fewer skin symptoms with Omicron versus Delta and the ancestral strains, and now this study shows it is true,” said Dr. Freeman, who is also principal investigator of the American Academy of Dermatology’s International Dermatology COVID-19 Registry.

The data also confirm that the skin is less likely to be involved than in past waves of COVID-19 infections.

“Up to this point, it was hard to know if we were seeing fewer referrals for COVID-related skin rashes or if clinicians had just become more comfortable with these rashes and were not referring them as often,” added Dr. Freeman, who was among the study coauthors.

Data captured from 348,691 patients

The data from the study was generated by 348,691 users in the United Kingdom of the ZOE COVID study app, a smartphone-based tool introduced relatively early in the pandemic. It asked users to provide demographic data, information on COVID-19 symptoms, including those involving the skin, and treatments. Of 33 COVID-related symptoms included in the app, five related to the skin (acral rash, burning rash, erythematopapular rash, urticarial rash, and unusual hair loss).

While the focus of this study was to compare skin manifestations during the Omicron wave with the Delta wave of COVID-19, the investigators also had data on the experience in 2020 with wild-type COVID-19 that preceded both variants. Overall, this showed a stepwise decline in skin symptoms overall, as well in as skin symptoms that occurred in the absence of systemic symptoms.

“The shift in the skin manifestations makes sense when you think about the change that is also being seen in the systemic symptoms,” said Dr. Freeman, referring to lower rates of cough and loss of smell but higher rates of sore throat and fatigue. “Omicron is achieving immune escape, which is why there is a shift in involved tissues,” she said in an interview.

Previous data collected during the wild-type COVID-19 stage of the pandemic by the same group of investigators showed that 17% of patients reported skin rash as the first symptom of COVID-19 infection, and 21% reported skin rash as the only clinical sign of infection.

In the Delta and Omicron waves, skin rash was an isolated initial symptom in only 0.8% and 0.5% of patients, respectively. (The authors noted that, in the United Kingdom, the first documented samples of the Delta variant were detected in October 2020, and the first documented samples of the Omicron variant were detected in November 2021.)

During the early stages of wild-type COVID, an acral rash was characteristic, occurring in 3.1% of patients, according to the U.K. data. In the Delta wave, acral rashes, at an incidence of 1.1% remained positively correlated with a diagnosis of COVID-19 infection. In the Omicron wave, acral rashes were observed in only 0.7% of patients and were no longer statistically correlated with a positive COVID diagnosis.


 

Characteristic cutaneous symptoms are evolving

Early in the course of the COVID-19 epidemic, more than 30 types of rashes were observed in patients with COVID-19 infection. Cutaneous symptoms continue to be diverse, but some, such as acral rash, are being seen less frequently. For example, the odds ratio of a positive COVID-19 diagnosis among those with an erythematopapular rash fell from 1.76 to 1.08 between the Delta and Omicron waves.

While specific cutaneous symptoms are less predictive of a diagnosis of COVID-19, clinicians should not discount cutaneous symptoms as a sign of disease, according to Veronique Bataille, MD, PhD, a consultant dermatologist at King’s College.

“You need to keep an open mind” regarding cutaneous signs and a diagnosis of COVID-19, Dr. Bataille, one of the coauthors of the U.K. report, said in an interview. In general, she considers a low threshold of suspicion appropriate. “If the patient has no past history of skin disease and no other triggers for a rash, then, in a high prevalence area, COVID must be suspected.”

In most cases, the rash resolves on its own, but Dr. Bataille emphasized the need for individualized care. Even as the risk of life-threatening COVID-19 infections appears to be diminishing with current variants, cutaneous manifestations can be severe.

“There are cases of long COVID affecting the skin, such as urticaria or a lichenoid erythematopapular rash, both of which can be very pruritic and difficult to control,” she said.

Dr. Freeman echoed the importance of an individualized approach. She agreed that most cutaneous symptoms are self-limited, but there are exceptions and treatments vary for the different types of skin involvement. “I think another point to consider when examining skin lesions is monkey pox. The fact that these are overlapping outbreaks should not be ignored. You need to be alert for both.”

Dr. Visconti, Dr. Freeman, and Dr. Bataille reported no potential conflicts of interest.

Skin symptoms, like systemic symptoms, differ by COVID-19 variant, according to a large retrospective study that compared clinical data from more than 300,000 participants in the United Kingdom during the Omicron and Delta waves.

Among the key findings, the study shows that skin involvement during the Omicron wave was less frequent than during the Delta wave (11.4% vs. 17.6%), skin symptoms generally resolved more quickly, and that the risk for skin symptoms was similar whether patients had or had not been vaccinated, according to a team led by Alessia Visconti, PhD, a research fellow in the department of twin research and genetic epidemiology, King’s College, London.

These data are consistent with the experience of those dermatologists who have been following this area closely, according to Esther Freeman, MD, PhD, associate professor of dermatology at Harvard Medical School and director of MGH Global Health Dermatology at Massachusetts General Hospital, both in Boston.

“Anecdotally, we thought we were seeing fewer skin symptoms with Omicron versus Delta and the ancestral strains, and now this study shows it is true,” said Dr. Freeman, who is also principal investigator of the American Academy of Dermatology’s International Dermatology COVID-19 Registry.

The data also confirm that the skin is less likely to be involved than in past waves of COVID-19 infections.

“Up to this point, it was hard to know if we were seeing fewer referrals for COVID-related skin rashes or if clinicians had just become more comfortable with these rashes and were not referring them as often,” added Dr. Freeman, who was among the study coauthors.

Data captured from 348,691 patients

The data from the study was generated by 348,691 users in the United Kingdom of the ZOE COVID study app, a smartphone-based tool introduced relatively early in the pandemic. It asked users to provide demographic data, information on COVID-19 symptoms, including those involving the skin, and treatments. Of 33 COVID-related symptoms included in the app, five related to the skin (acral rash, burning rash, erythematopapular rash, urticarial rash, and unusual hair loss).

While the focus of this study was to compare skin manifestations during the Omicron wave with the Delta wave of COVID-19, the investigators also had data on the experience in 2020 with wild-type COVID-19 that preceded both variants. Overall, this showed a stepwise decline in skin symptoms overall, as well in as skin symptoms that occurred in the absence of systemic symptoms.

“The shift in the skin manifestations makes sense when you think about the change that is also being seen in the systemic symptoms,” said Dr. Freeman, referring to lower rates of cough and loss of smell but higher rates of sore throat and fatigue. “Omicron is achieving immune escape, which is why there is a shift in involved tissues,” she said in an interview.

Previous data collected during the wild-type COVID-19 stage of the pandemic by the same group of investigators showed that 17% of patients reported skin rash as the first symptom of COVID-19 infection, and 21% reported skin rash as the only clinical sign of infection.

In the Delta and Omicron waves, skin rash was an isolated initial symptom in only 0.8% and 0.5% of patients, respectively. (The authors noted that, in the United Kingdom, the first documented samples of the Delta variant were detected in October 2020, and the first documented samples of the Omicron variant were detected in November 2021.)

During the early stages of wild-type COVID, an acral rash was characteristic, occurring in 3.1% of patients, according to the U.K. data. In the Delta wave, acral rashes, at an incidence of 1.1% remained positively correlated with a diagnosis of COVID-19 infection. In the Omicron wave, acral rashes were observed in only 0.7% of patients and were no longer statistically correlated with a positive COVID diagnosis.


 

Characteristic cutaneous symptoms are evolving

Early in the course of the COVID-19 epidemic, more than 30 types of rashes were observed in patients with COVID-19 infection. Cutaneous symptoms continue to be diverse, but some, such as acral rash, are being seen less frequently. For example, the odds ratio of a positive COVID-19 diagnosis among those with an erythematopapular rash fell from 1.76 to 1.08 between the Delta and Omicron waves.

While specific cutaneous symptoms are less predictive of a diagnosis of COVID-19, clinicians should not discount cutaneous symptoms as a sign of disease, according to Veronique Bataille, MD, PhD, a consultant dermatologist at King’s College.

“You need to keep an open mind” regarding cutaneous signs and a diagnosis of COVID-19, Dr. Bataille, one of the coauthors of the U.K. report, said in an interview. In general, she considers a low threshold of suspicion appropriate. “If the patient has no past history of skin disease and no other triggers for a rash, then, in a high prevalence area, COVID must be suspected.”

In most cases, the rash resolves on its own, but Dr. Bataille emphasized the need for individualized care. Even as the risk of life-threatening COVID-19 infections appears to be diminishing with current variants, cutaneous manifestations can be severe.

“There are cases of long COVID affecting the skin, such as urticaria or a lichenoid erythematopapular rash, both of which can be very pruritic and difficult to control,” she said.

Dr. Freeman echoed the importance of an individualized approach. She agreed that most cutaneous symptoms are self-limited, but there are exceptions and treatments vary for the different types of skin involvement. “I think another point to consider when examining skin lesions is monkey pox. The fact that these are overlapping outbreaks should not be ignored. You need to be alert for both.”

Dr. Visconti, Dr. Freeman, and Dr. Bataille reported no potential conflicts of interest.

Skin symptoms, like systemic symptoms, differ by COVID-19 variant, according to a large retrospective study that compared clinical data from more than 300,000 participants in the United Kingdom during the Omicron and Delta waves.

Among the key findings, the study shows that skin involvement during the Omicron wave was less frequent than during the Delta wave (11.4% vs. 17.6%), skin symptoms generally resolved more quickly, and that the risk for skin symptoms was similar whether patients had or had not been vaccinated, according to a team led by Alessia Visconti, PhD, a research fellow in the department of twin research and genetic epidemiology, King’s College, London.

These data are consistent with the experience of those dermatologists who have been following this area closely, according to Esther Freeman, MD, PhD, associate professor of dermatology at Harvard Medical School and director of MGH Global Health Dermatology at Massachusetts General Hospital, both in Boston.

“Anecdotally, we thought we were seeing fewer skin symptoms with Omicron versus Delta and the ancestral strains, and now this study shows it is true,” said Dr. Freeman, who is also principal investigator of the American Academy of Dermatology’s International Dermatology COVID-19 Registry.

The data also confirm that the skin is less likely to be involved than in past waves of COVID-19 infections.

“Up to this point, it was hard to know if we were seeing fewer referrals for COVID-related skin rashes or if clinicians had just become more comfortable with these rashes and were not referring them as often,” added Dr. Freeman, who was among the study coauthors.

Data captured from 348,691 patients

The data from the study was generated by 348,691 users in the United Kingdom of the ZOE COVID study app, a smartphone-based tool introduced relatively early in the pandemic. It asked users to provide demographic data, information on COVID-19 symptoms, including those involving the skin, and treatments. Of 33 COVID-related symptoms included in the app, five related to the skin (acral rash, burning rash, erythematopapular rash, urticarial rash, and unusual hair loss).

While the focus of this study was to compare skin manifestations during the Omicron wave with the Delta wave of COVID-19, the investigators also had data on the experience in 2020 with wild-type COVID-19 that preceded both variants. Overall, this showed a stepwise decline in skin symptoms overall, as well in as skin symptoms that occurred in the absence of systemic symptoms.

“The shift in the skin manifestations makes sense when you think about the change that is also being seen in the systemic symptoms,” said Dr. Freeman, referring to lower rates of cough and loss of smell but higher rates of sore throat and fatigue. “Omicron is achieving immune escape, which is why there is a shift in involved tissues,” she said in an interview.

Previous data collected during the wild-type COVID-19 stage of the pandemic by the same group of investigators showed that 17% of patients reported skin rash as the first symptom of COVID-19 infection, and 21% reported skin rash as the only clinical sign of infection.

In the Delta and Omicron waves, skin rash was an isolated initial symptom in only 0.8% and 0.5% of patients, respectively. (The authors noted that, in the United Kingdom, the first documented samples of the Delta variant were detected in October 2020, and the first documented samples of the Omicron variant were detected in November 2021.)

During the early stages of wild-type COVID, an acral rash was characteristic, occurring in 3.1% of patients, according to the U.K. data. In the Delta wave, acral rashes, at an incidence of 1.1% remained positively correlated with a diagnosis of COVID-19 infection. In the Omicron wave, acral rashes were observed in only 0.7% of patients and were no longer statistically correlated with a positive COVID diagnosis.


 

Characteristic cutaneous symptoms are evolving

Early in the course of the COVID-19 epidemic, more than 30 types of rashes were observed in patients with COVID-19 infection. Cutaneous symptoms continue to be diverse, but some, such as acral rash, are being seen less frequently. For example, the odds ratio of a positive COVID-19 diagnosis among those with an erythematopapular rash fell from 1.76 to 1.08 between the Delta and Omicron waves.

While specific cutaneous symptoms are less predictive of a diagnosis of COVID-19, clinicians should not discount cutaneous symptoms as a sign of disease, according to Veronique Bataille, MD, PhD, a consultant dermatologist at King’s College.

“You need to keep an open mind” regarding cutaneous signs and a diagnosis of COVID-19, Dr. Bataille, one of the coauthors of the U.K. report, said in an interview. In general, she considers a low threshold of suspicion appropriate. “If the patient has no past history of skin disease and no other triggers for a rash, then, in a high prevalence area, COVID must be suspected.”

In most cases, the rash resolves on its own, but Dr. Bataille emphasized the need for individualized care. Even as the risk of life-threatening COVID-19 infections appears to be diminishing with current variants, cutaneous manifestations can be severe.

“There are cases of long COVID affecting the skin, such as urticaria or a lichenoid erythematopapular rash, both of which can be very pruritic and difficult to control,” she said.

Dr. Freeman echoed the importance of an individualized approach. She agreed that most cutaneous symptoms are self-limited, but there are exceptions and treatments vary for the different types of skin involvement. “I think another point to consider when examining skin lesions is monkey pox. The fact that these are overlapping outbreaks should not be ignored. You need to be alert for both.”

Dr. Visconti, Dr. Freeman, and Dr. Bataille reported no potential conflicts of interest.

Evusheld (AstraZeneca), a medication used to prevent SARS-CoV-2 infection in patients at high risk, has problems: Namely, that supplies of the potentially lifesaving drug outweigh demand.

At least 7 million people who are immunocompromised could benefit from it, as could many others who are undergoing cancer treatment, have received a transplant, or who are allergic to the COVID-19 vaccines. The medication has laboratory-produced antibodies against SARS-CoV-2 and helps the body protect itself. It can slash the chances of becoming infected by 77%, according to the U.S. Food and Drug Administration.

And it’s free to eligible patients (although there may be an out-of-pocket administrative fee in some cases).

Despite all those lifesaving benefits, fewer than 25% of available doses have been used.

To meet demand, the Biden administration secured 1.7 million doses of the medicine, which was granted emergency use authorization by the FDA in December 2021. As of July 25, however, 793,348 doses have been ordered by the administration sites, and only 398,181 doses have been reported as used, a spokesperson for the Department of Health & Human Services tells this news organization.

Each week, a certain amount of doses from the 1.7 million dose stockpile is made available to state and territorial health departments. States have not been asking for their full allotment, the spokesperson said July 28.

Now, HHS and AstraZeneca have taken a number of steps to increase awareness of the medication and access to it.

• On July 27, HHS announced that individual providers and smaller sites of care that don’t currently receive Evusheld through the federal distribution process via the HHS Health Partner Order Portal can now order up to three patient courses of the medicine. These can be 
• Health care providers can use the HHS’s COVID-19 Therapeutics Locator to find Evusheld in their area.
• AstraZeneca has launched a new website with educational materials and says it is working closely with patient and professional groups to inform patients and health care providers.
• A direct-to-consumer ad launched on June 22 and will run in the United States online and on TV (Yahoo, Fox, CBS Sports, MSN, ESPN) and be amplified on social and digital channels through year’s end, an AstraZeneca spokesperson said in an interview.
• AstraZeneca set up a toll-free number for providers: 1-833-EVUSHLD.

Evusheld includes two monoclonal antibodies, tixagevimab and cilgavimab. The medication is given as two consecutive intramuscular injections during a single visit to a doctor’s office, infusion center, or other health care facility. The antibodies bind to the SARS-CoV-2 spike protein and prevent the virus from getting into human cells and infecting them. It’s authorized for use in children and adults aged 12 years and older who weigh at least 88 pounds.

Studies have found that the medication decreases the risk of getting COVID-19 for up to 6 months after it is given. The FDA recommends repeat dosing every 6 months with the doses of 300 mg of each monoclonal antibody. In clinical trials, Evusheld reduced the incidence of COVID-19 symptomatic illness by 77%, compared with placebo.

Physicians monitor patients for an hour after administering Evusheld for allergic reactions. Other possible side effects include cardiac events, but they are not common.
 

Doctors and patients weigh in

Physicians – and patients – from the United States to the United Kingdom and beyond are questioning why the medication is underused while lauding the recent efforts to expand access and increase awareness.

The U.S. federal government may have underestimated the amount of communication needed to increase awareness of the medication and its applications, said infectious disease specialist William Schaffner, MD, professor of preventive medicine at Vanderbilt University School of Medicine, Nashville, Tenn.

“HHS hasn’t made a major educational effort to promote it,” he said in an interview.

Many physicians who need to know about it, such as transplant doctors and rheumatologists, are outside the typical public health communications loop, he said.

Eric Topol, MD, director of the Scripps Research Transational Institute and editor-in-chief of Medscape, has taken to social media to bemoan the lack of awareness.

Another infectious disease expert agrees. “In my experience, the awareness of Evusheld is low amongst many patients as well as many providers,” said Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security, Baltimore.

“Initially, there were scarce supplies of the drug, and certain hospital systems tiered eligibility based on degrees of immunosuppression, and only the most immunosuppressed were proactively approached for treatment.”

“Also, many community hospitals never initially ordered Evusheld – they may have been crowded out by academic centers who treat many more immunosuppressed patients and may not currently see it as a priority,” Dr. Adalja said in an interview. “As such, many immunosuppressed patients would have to seek treatment at academic medical centers, where the drug is more likely to be available.”

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

Evusheld (AstraZeneca), a medication used to prevent SARS-CoV-2 infection in patients at high risk, has problems: Namely, that supplies of the potentially lifesaving drug outweigh demand.

At least 7 million people who are immunocompromised could benefit from it, as could many others who are undergoing cancer treatment, have received a transplant, or who are allergic to the COVID-19 vaccines. The medication has laboratory-produced antibodies against SARS-CoV-2 and helps the body protect itself. It can slash the chances of becoming infected by 77%, according to the U.S. Food and Drug Administration.

And it’s free to eligible patients (although there may be an out-of-pocket administrative fee in some cases).

Despite all those lifesaving benefits, fewer than 25% of available doses have been used.

To meet demand, the Biden administration secured 1.7 million doses of the medicine, which was granted emergency use authorization by the FDA in December 2021. As of July 25, however, 793,348 doses have been ordered by the administration sites, and only 398,181 doses have been reported as used, a spokesperson for the Department of Health & Human Services tells this news organization.

Each week, a certain amount of doses from the 1.7 million dose stockpile is made available to state and territorial health departments. States have not been asking for their full allotment, the spokesperson said July 28.

Now, HHS and AstraZeneca have taken a number of steps to increase awareness of the medication and access to it.

• On July 27, HHS announced that individual providers and smaller sites of care that don’t currently receive Evusheld through the federal distribution process via the HHS Health Partner Order Portal can now order up to three patient courses of the medicine. These can be 
• Health care providers can use the HHS’s COVID-19 Therapeutics Locator to find Evusheld in their area.
• AstraZeneca has launched a new website with educational materials and says it is working closely with patient and professional groups to inform patients and health care providers.
• A direct-to-consumer ad launched on June 22 and will run in the United States online and on TV (Yahoo, Fox, CBS Sports, MSN, ESPN) and be amplified on social and digital channels through year’s end, an AstraZeneca spokesperson said in an interview.
• AstraZeneca set up a toll-free number for providers: 1-833-EVUSHLD.

Evusheld includes two monoclonal antibodies, tixagevimab and cilgavimab. The medication is given as two consecutive intramuscular injections during a single visit to a doctor’s office, infusion center, or other health care facility. The antibodies bind to the SARS-CoV-2 spike protein and prevent the virus from getting into human cells and infecting them. It’s authorized for use in children and adults aged 12 years and older who weigh at least 88 pounds.

Studies have found that the medication decreases the risk of getting COVID-19 for up to 6 months after it is given. The FDA recommends repeat dosing every 6 months with the doses of 300 mg of each monoclonal antibody. In clinical trials, Evusheld reduced the incidence of COVID-19 symptomatic illness by 77%, compared with placebo.

Physicians monitor patients for an hour after administering Evusheld for allergic reactions. Other possible side effects include cardiac events, but they are not common.
 

Doctors and patients weigh in

Physicians – and patients – from the United States to the United Kingdom and beyond are questioning why the medication is underused while lauding the recent efforts to expand access and increase awareness.

The U.S. federal government may have underestimated the amount of communication needed to increase awareness of the medication and its applications, said infectious disease specialist William Schaffner, MD, professor of preventive medicine at Vanderbilt University School of Medicine, Nashville, Tenn.

“HHS hasn’t made a major educational effort to promote it,” he said in an interview.

Many physicians who need to know about it, such as transplant doctors and rheumatologists, are outside the typical public health communications loop, he said.

Eric Topol, MD, director of the Scripps Research Transational Institute and editor-in-chief of Medscape, has taken to social media to bemoan the lack of awareness.

Another infectious disease expert agrees. “In my experience, the awareness of Evusheld is low amongst many patients as well as many providers,” said Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security, Baltimore.

“Initially, there were scarce supplies of the drug, and certain hospital systems tiered eligibility based on degrees of immunosuppression, and only the most immunosuppressed were proactively approached for treatment.”

“Also, many community hospitals never initially ordered Evusheld – they may have been crowded out by academic centers who treat many more immunosuppressed patients and may not currently see it as a priority,” Dr. Adalja said in an interview. “As such, many immunosuppressed patients would have to seek treatment at academic medical centers, where the drug is more likely to be available.”

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

Evusheld (AstraZeneca), a medication used to prevent SARS-CoV-2 infection in patients at high risk, has problems: Namely, that supplies of the potentially lifesaving drug outweigh demand.

At least 7 million people who are immunocompromised could benefit from it, as could many others who are undergoing cancer treatment, have received a transplant, or who are allergic to the COVID-19 vaccines. The medication has laboratory-produced antibodies against SARS-CoV-2 and helps the body protect itself. It can slash the chances of becoming infected by 77%, according to the U.S. Food and Drug Administration.

And it’s free to eligible patients (although there may be an out-of-pocket administrative fee in some cases).

Despite all those lifesaving benefits, fewer than 25% of available doses have been used.

To meet demand, the Biden administration secured 1.7 million doses of the medicine, which was granted emergency use authorization by the FDA in December 2021. As of July 25, however, 793,348 doses have been ordered by the administration sites, and only 398,181 doses have been reported as used, a spokesperson for the Department of Health & Human Services tells this news organization.

Each week, a certain amount of doses from the 1.7 million dose stockpile is made available to state and territorial health departments. States have not been asking for their full allotment, the spokesperson said July 28.

Now, HHS and AstraZeneca have taken a number of steps to increase awareness of the medication and access to it.

• On July 27, HHS announced that individual providers and smaller sites of care that don’t currently receive Evusheld through the federal distribution process via the HHS Health Partner Order Portal can now order up to three patient courses of the medicine. These can be 
• Health care providers can use the HHS’s COVID-19 Therapeutics Locator to find Evusheld in their area.
• AstraZeneca has launched a new website with educational materials and says it is working closely with patient and professional groups to inform patients and health care providers.
• A direct-to-consumer ad launched on June 22 and will run in the United States online and on TV (Yahoo, Fox, CBS Sports, MSN, ESPN) and be amplified on social and digital channels through year’s end, an AstraZeneca spokesperson said in an interview.
• AstraZeneca set up a toll-free number for providers: 1-833-EVUSHLD.

Evusheld includes two monoclonal antibodies, tixagevimab and cilgavimab. The medication is given as two consecutive intramuscular injections during a single visit to a doctor’s office, infusion center, or other health care facility. The antibodies bind to the SARS-CoV-2 spike protein and prevent the virus from getting into human cells and infecting them. It’s authorized for use in children and adults aged 12 years and older who weigh at least 88 pounds.

Studies have found that the medication decreases the risk of getting COVID-19 for up to 6 months after it is given. The FDA recommends repeat dosing every 6 months with the doses of 300 mg of each monoclonal antibody. In clinical trials, Evusheld reduced the incidence of COVID-19 symptomatic illness by 77%, compared with placebo.

Physicians monitor patients for an hour after administering Evusheld for allergic reactions. Other possible side effects include cardiac events, but they are not common.
 

Doctors and patients weigh in

Physicians – and patients – from the United States to the United Kingdom and beyond are questioning why the medication is underused while lauding the recent efforts to expand access and increase awareness.

The U.S. federal government may have underestimated the amount of communication needed to increase awareness of the medication and its applications, said infectious disease specialist William Schaffner, MD, professor of preventive medicine at Vanderbilt University School of Medicine, Nashville, Tenn.

“HHS hasn’t made a major educational effort to promote it,” he said in an interview.

Many physicians who need to know about it, such as transplant doctors and rheumatologists, are outside the typical public health communications loop, he said.

Eric Topol, MD, director of the Scripps Research Transational Institute and editor-in-chief of Medscape, has taken to social media to bemoan the lack of awareness.

Another infectious disease expert agrees. “In my experience, the awareness of Evusheld is low amongst many patients as well as many providers,” said Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security, Baltimore.

“Initially, there were scarce supplies of the drug, and certain hospital systems tiered eligibility based on degrees of immunosuppression, and only the most immunosuppressed were proactively approached for treatment.”

“Also, many community hospitals never initially ordered Evusheld – they may have been crowded out by academic centers who treat many more immunosuppressed patients and may not currently see it as a priority,” Dr. Adalja said in an interview. “As such, many immunosuppressed patients would have to seek treatment at academic medical centers, where the drug is more likely to be available.”

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

The Food and Drug Administration has approved roflumilast 0.3% cream for the topical treatment of plaque psoriasis, “including intertriginous areas,” in patients aged 12 years and older.

Roflumilast is a selective inhibitor of phosphodiesterase 4 (PDE4), the first approved for treating psoriasis, according to manufacturer Arcutis Biotherapeutics. The company announced the approval on July 29. Oral roflumilast (Daliresp ) was approved in 2011 for treating chronic obstructive pulmonary disease (COPD).“It’s a breakthrough topical therapy,” says Mark G. Lebwohl, MD, dean of clinical therapeutics and professor of dermatology, Icahn School of Medicine at Mount Sinai, New York, and principal investigator in trials of topical roflumilast. In an interview, Dr. Lebwohl noted that the treatment significantly reduced psoriasis symptoms in both short- and long-term trials.

In addition, two features of this treatment set it apart from other topical psoriasis treatments, he said. Roflumilast is not a steroid, so does not have the risk for topical steroid-related side effects associated with chronic use, and, in clinical trials, topical roflumilast was effective in treating psoriasis in intertriginous areas, including the buttocks, underarms, and beneath the breasts, which are difficult to treat.

FDA approval is based on data from two phase 3 randomized, double-blind, vehicle-controlled trials, according to Arcutis. The primary endpoint was Investigator Global Assessment (IGA) success, defined as clear or almost clear with at least a two-grade improvement from baseline, and at least a two-grade IGA score improvement from baseline at 8 weeks.

At 8 weeks, 42.4% and 37.5% of the patients treated with topical roflumilast achieved an IGA success rate compared with 6.1% and 6.9% in the control groups, respectively (P < .0001 for both studies).

Treated patients also experienced significant improvements compared with those in the vehicle groups in secondary endpoints in the trials: Those included Intertriginous IGA (I-IGA) Success, Psoriasis Area Severity Index–75 (PASI-75), reductions in itch based on the Worst Itch–Numerical Rating Scale (WI-NRS), and self-reported psoriasis symptoms diary (PSD).

In the studies, 72% and 68% of patients treated with roflumilast met the I-IGA endpoint at 8 weeks versus 14% and 17%, respectively, of those on vehicle (P < .0001 for both studies).  

In addition, by week 2, some participants treated with roflumilast had experienced reduced itchiness in both studies. At 8 weeks, among those with a WI-NRS score of 4 or more at baseline, 67% and 69% of the treated patients had at least a four-point reduction in the WI-NRS versus 26% and 33%, respectively, among those on vehicle (P < .0001 for both studies), according to the company.

In general, the cream was well tolerated. There were reports of diarrhea (3%), headache (2%), insomnia (1%), nausea (1%), application-site pain (1%), upper respiratory tract infections (1%), and urinary tract infections (1%). However, Dr. Lebwohl noted that these events were also observed in the control group.

“The study was unequivocal about the improvement in the intertriginous sites,” Dr. Lebwohl said. He contrasts that to the data from other nonsteroidal topicals, which he said can be associated with a rash or irritation in sensitive areas.

Dr. Lebwohl noted that PDE4 is an enzyme that increases inflammation and decreases anti-inflammatory mediators and that inhibiting PDE4 may interrupt some of the inflammation response responsible for psoriasis symptoms, as it has for other conditions such as atopic dermatitis. Data from the 8-week phase 3 trials and yearlong phase 2b, open-label studies support that hypothesis.

“I’m always excited for new psoriasis treatments to broaden our treatment armamentarium,” said Lauren E. Ploch, MD, a dermatologist who practices in Augusta, Ga., and Aiken, S.C., who was asked to comment on the approval.

Even a symptom that seems benign, like itching, Dr. Ploch added, can lead to reduced sleep and increased irritability. Referring to the data on the treatment in the sensitive, intertriginous areas, she noted that the skin in these areas is often thinner, so treatment with steroids can cause further thinning and damage to the skin. If roflumilast doesn’t cause burning, itching, or thinning, it will be a great option to treat these areas, she said in an interview. She was not involved in the trials.

Roflumilast cream will be marketed under the trade name Zoryve, and is expected to be available by mid-August, according to Arcutis.

Roflumilast cream is also under review in Canada for treatment of plaque psoriasis in adults and adolescents.

The studies were funded by Arcutis Biotherapeutics. Dr. Lebwohl reported receiving grant support and consulting fees from Arcutis. Dr. Ploch reports no relevant financial relationships.

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

The Food and Drug Administration has approved roflumilast 0.3% cream for the topical treatment of plaque psoriasis, “including intertriginous areas,” in patients aged 12 years and older.

Roflumilast is a selective inhibitor of phosphodiesterase 4 (PDE4), the first approved for treating psoriasis, according to manufacturer Arcutis Biotherapeutics. The company announced the approval on July 29. Oral roflumilast (Daliresp ) was approved in 2011 for treating chronic obstructive pulmonary disease (COPD).“It’s a breakthrough topical therapy,” says Mark G. Lebwohl, MD, dean of clinical therapeutics and professor of dermatology, Icahn School of Medicine at Mount Sinai, New York, and principal investigator in trials of topical roflumilast. In an interview, Dr. Lebwohl noted that the treatment significantly reduced psoriasis symptoms in both short- and long-term trials.

In addition, two features of this treatment set it apart from other topical psoriasis treatments, he said. Roflumilast is not a steroid, so does not have the risk for topical steroid-related side effects associated with chronic use, and, in clinical trials, topical roflumilast was effective in treating psoriasis in intertriginous areas, including the buttocks, underarms, and beneath the breasts, which are difficult to treat.

FDA approval is based on data from two phase 3 randomized, double-blind, vehicle-controlled trials, according to Arcutis. The primary endpoint was Investigator Global Assessment (IGA) success, defined as clear or almost clear with at least a two-grade improvement from baseline, and at least a two-grade IGA score improvement from baseline at 8 weeks.

At 8 weeks, 42.4% and 37.5% of the patients treated with topical roflumilast achieved an IGA success rate compared with 6.1% and 6.9% in the control groups, respectively (P < .0001 for both studies).

Treated patients also experienced significant improvements compared with those in the vehicle groups in secondary endpoints in the trials: Those included Intertriginous IGA (I-IGA) Success, Psoriasis Area Severity Index–75 (PASI-75), reductions in itch based on the Worst Itch–Numerical Rating Scale (WI-NRS), and self-reported psoriasis symptoms diary (PSD).

In the studies, 72% and 68% of patients treated with roflumilast met the I-IGA endpoint at 8 weeks versus 14% and 17%, respectively, of those on vehicle (P < .0001 for both studies).  

In addition, by week 2, some participants treated with roflumilast had experienced reduced itchiness in both studies. At 8 weeks, among those with a WI-NRS score of 4 or more at baseline, 67% and 69% of the treated patients had at least a four-point reduction in the WI-NRS versus 26% and 33%, respectively, among those on vehicle (P < .0001 for both studies), according to the company.

In general, the cream was well tolerated. There were reports of diarrhea (3%), headache (2%), insomnia (1%), nausea (1%), application-site pain (1%), upper respiratory tract infections (1%), and urinary tract infections (1%). However, Dr. Lebwohl noted that these events were also observed in the control group.

“The study was unequivocal about the improvement in the intertriginous sites,” Dr. Lebwohl said. He contrasts that to the data from other nonsteroidal topicals, which he said can be associated with a rash or irritation in sensitive areas.

Dr. Lebwohl noted that PDE4 is an enzyme that increases inflammation and decreases anti-inflammatory mediators and that inhibiting PDE4 may interrupt some of the inflammation response responsible for psoriasis symptoms, as it has for other conditions such as atopic dermatitis. Data from the 8-week phase 3 trials and yearlong phase 2b, open-label studies support that hypothesis.

“I’m always excited for new psoriasis treatments to broaden our treatment armamentarium,” said Lauren E. Ploch, MD, a dermatologist who practices in Augusta, Ga., and Aiken, S.C., who was asked to comment on the approval.

Even a symptom that seems benign, like itching, Dr. Ploch added, can lead to reduced sleep and increased irritability. Referring to the data on the treatment in the sensitive, intertriginous areas, she noted that the skin in these areas is often thinner, so treatment with steroids can cause further thinning and damage to the skin. If roflumilast doesn’t cause burning, itching, or thinning, it will be a great option to treat these areas, she said in an interview. She was not involved in the trials.

Roflumilast cream will be marketed under the trade name Zoryve, and is expected to be available by mid-August, according to Arcutis.

Roflumilast cream is also under review in Canada for treatment of plaque psoriasis in adults and adolescents.

The studies were funded by Arcutis Biotherapeutics. Dr. Lebwohl reported receiving grant support and consulting fees from Arcutis. Dr. Ploch reports no relevant financial relationships.

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

The Food and Drug Administration has approved roflumilast 0.3% cream for the topical treatment of plaque psoriasis, “including intertriginous areas,” in patients aged 12 years and older.

Roflumilast is a selective inhibitor of phosphodiesterase 4 (PDE4), the first approved for treating psoriasis, according to manufacturer Arcutis Biotherapeutics. The company announced the approval on July 29. Oral roflumilast (Daliresp ) was approved in 2011 for treating chronic obstructive pulmonary disease (COPD).“It’s a breakthrough topical therapy,” says Mark G. Lebwohl, MD, dean of clinical therapeutics and professor of dermatology, Icahn School of Medicine at Mount Sinai, New York, and principal investigator in trials of topical roflumilast. In an interview, Dr. Lebwohl noted that the treatment significantly reduced psoriasis symptoms in both short- and long-term trials.

In addition, two features of this treatment set it apart from other topical psoriasis treatments, he said. Roflumilast is not a steroid, so does not have the risk for topical steroid-related side effects associated with chronic use, and, in clinical trials, topical roflumilast was effective in treating psoriasis in intertriginous areas, including the buttocks, underarms, and beneath the breasts, which are difficult to treat.

FDA approval is based on data from two phase 3 randomized, double-blind, vehicle-controlled trials, according to Arcutis. The primary endpoint was Investigator Global Assessment (IGA) success, defined as clear or almost clear with at least a two-grade improvement from baseline, and at least a two-grade IGA score improvement from baseline at 8 weeks.

At 8 weeks, 42.4% and 37.5% of the patients treated with topical roflumilast achieved an IGA success rate compared with 6.1% and 6.9% in the control groups, respectively (P < .0001 for both studies).

Treated patients also experienced significant improvements compared with those in the vehicle groups in secondary endpoints in the trials: Those included Intertriginous IGA (I-IGA) Success, Psoriasis Area Severity Index–75 (PASI-75), reductions in itch based on the Worst Itch–Numerical Rating Scale (WI-NRS), and self-reported psoriasis symptoms diary (PSD).

In the studies, 72% and 68% of patients treated with roflumilast met the I-IGA endpoint at 8 weeks versus 14% and 17%, respectively, of those on vehicle (P < .0001 for both studies).  

In addition, by week 2, some participants treated with roflumilast had experienced reduced itchiness in both studies. At 8 weeks, among those with a WI-NRS score of 4 or more at baseline, 67% and 69% of the treated patients had at least a four-point reduction in the WI-NRS versus 26% and 33%, respectively, among those on vehicle (P < .0001 for both studies), according to the company.

In general, the cream was well tolerated. There were reports of diarrhea (3%), headache (2%), insomnia (1%), nausea (1%), application-site pain (1%), upper respiratory tract infections (1%), and urinary tract infections (1%). However, Dr. Lebwohl noted that these events were also observed in the control group.

“The study was unequivocal about the improvement in the intertriginous sites,” Dr. Lebwohl said. He contrasts that to the data from other nonsteroidal topicals, which he said can be associated with a rash or irritation in sensitive areas.

Dr. Lebwohl noted that PDE4 is an enzyme that increases inflammation and decreases anti-inflammatory mediators and that inhibiting PDE4 may interrupt some of the inflammation response responsible for psoriasis symptoms, as it has for other conditions such as atopic dermatitis. Data from the 8-week phase 3 trials and yearlong phase 2b, open-label studies support that hypothesis.

“I’m always excited for new psoriasis treatments to broaden our treatment armamentarium,” said Lauren E. Ploch, MD, a dermatologist who practices in Augusta, Ga., and Aiken, S.C., who was asked to comment on the approval.

Even a symptom that seems benign, like itching, Dr. Ploch added, can lead to reduced sleep and increased irritability. Referring to the data on the treatment in the sensitive, intertriginous areas, she noted that the skin in these areas is often thinner, so treatment with steroids can cause further thinning and damage to the skin. If roflumilast doesn’t cause burning, itching, or thinning, it will be a great option to treat these areas, she said in an interview. She was not involved in the trials.

Roflumilast cream will be marketed under the trade name Zoryve, and is expected to be available by mid-August, according to Arcutis.

Roflumilast cream is also under review in Canada for treatment of plaque psoriasis in adults and adolescents.

The studies were funded by Arcutis Biotherapeutics. Dr. Lebwohl reported receiving grant support and consulting fees from Arcutis. Dr. Ploch reports no relevant financial relationships.

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

In the last 2 decades, the number of women receiving awards from the American College of Rheumatology, European Alliance of Associations for Rheumatology, and the British Society for Rheumatology has steadily increased, but the absolute percentage of female prize winners remains lower than male winners across the 41 total awards given by the three organizations, according to Thorsten Halling and colleagues at Heinrich-Heine-University in Düsseldorf, Germany.

The overall number of awards given by the three groups rose by 10% over the past 2 years. In 2021, 40% of awards given by the ACR went to females, compared with 48% by EULAR, and 50% by the BSR. However, the most prestigious prizes awarded by these groups were given less often to women, according to the researchers, who published their results online July 27, 2022, in The Lancet Rheumatology. They noted that during 2017-2021, just one in five top prizes from ACR went to a woman; once (20%) for the Presidential Gold Medal, and 26 times (23%) for the ACR Master Designation. During the same time period, only one woman (11%) received the EULAR Meritorious Service Award. In 2022, the EULAR Health Professionals in Rheumatology Lifetime Achievement Award was inaugurated and given to Christina Opava. As for the most important prizes of the BSR, the corresponding numbers for female recipients are 25% for the Michael Mason Award and 33% for the Garrod Award.” This pattern did not seem to change in 2022 at the BSR and EULAR annual meetings; the 2022 ACR annual meeting is in November.

ptasha/Getty Images

The trend is also seen in others fields, noted the researchers, who cited only one woman winning mathematics’ Fields Medal since it began in 1936 and female scientists winning only 7% of the Nobel Prize awards in the categories physiology or medicine, physics, and chemistry. In one larger study of 141 international research prizes that were awarded 3,445 times during 2001-2020, only 262 recipients were women.

Changing the status quo begins with awareness, according to the authors, who propose three strategies for prize juries to follow to raise the number of female awardees. “First, it is important to stimulate diversity among both nominees and the members of prize committees. Efforts to diversify the pool of nominees have already been initiated by large science prize players, such as the Royal Academy of Sciences in Sweden and the Wolf Foundation in Israel. This diversity should not only take gender into account, but also geographical region, ethnicity, and age. In the prize statutes, we recommend that the biological age of the applicants should no longer play a role for young scientist awards, but only the academic age. Second, if prizes are to be named after a person or people, we suggest that they should increasingly honor rheumatologists who are women to further increase their visibility in the field of rheumatology. We can note that, so far, no single award is named after a rheumatologist who is a woman. Third, we are convinced that more transparency around the nomination procedure will promote gender equity among the future prize winners.”

The authors had no conflicts of interest to declare.

In the last 2 decades, the number of women receiving awards from the American College of Rheumatology, European Alliance of Associations for Rheumatology, and the British Society for Rheumatology has steadily increased, but the absolute percentage of female prize winners remains lower than male winners across the 41 total awards given by the three organizations, according to Thorsten Halling and colleagues at Heinrich-Heine-University in Düsseldorf, Germany.

The overall number of awards given by the three groups rose by 10% over the past 2 years. In 2021, 40% of awards given by the ACR went to females, compared with 48% by EULAR, and 50% by the BSR. However, the most prestigious prizes awarded by these groups were given less often to women, according to the researchers, who published their results online July 27, 2022, in The Lancet Rheumatology. They noted that during 2017-2021, just one in five top prizes from ACR went to a woman; once (20%) for the Presidential Gold Medal, and 26 times (23%) for the ACR Master Designation. During the same time period, only one woman (11%) received the EULAR Meritorious Service Award. In 2022, the EULAR Health Professionals in Rheumatology Lifetime Achievement Award was inaugurated and given to Christina Opava. As for the most important prizes of the BSR, the corresponding numbers for female recipients are 25% for the Michael Mason Award and 33% for the Garrod Award.” This pattern did not seem to change in 2022 at the BSR and EULAR annual meetings; the 2022 ACR annual meeting is in November.

ptasha/Getty Images

The trend is also seen in others fields, noted the researchers, who cited only one woman winning mathematics’ Fields Medal since it began in 1936 and female scientists winning only 7% of the Nobel Prize awards in the categories physiology or medicine, physics, and chemistry. In one larger study of 141 international research prizes that were awarded 3,445 times during 2001-2020, only 262 recipients were women.

Changing the status quo begins with awareness, according to the authors, who propose three strategies for prize juries to follow to raise the number of female awardees. “First, it is important to stimulate diversity among both nominees and the members of prize committees. Efforts to diversify the pool of nominees have already been initiated by large science prize players, such as the Royal Academy of Sciences in Sweden and the Wolf Foundation in Israel. This diversity should not only take gender into account, but also geographical region, ethnicity, and age. In the prize statutes, we recommend that the biological age of the applicants should no longer play a role for young scientist awards, but only the academic age. Second, if prizes are to be named after a person or people, we suggest that they should increasingly honor rheumatologists who are women to further increase their visibility in the field of rheumatology. We can note that, so far, no single award is named after a rheumatologist who is a woman. Third, we are convinced that more transparency around the nomination procedure will promote gender equity among the future prize winners.”

The authors had no conflicts of interest to declare.

In the last 2 decades, the number of women receiving awards from the American College of Rheumatology, European Alliance of Associations for Rheumatology, and the British Society for Rheumatology has steadily increased, but the absolute percentage of female prize winners remains lower than male winners across the 41 total awards given by the three organizations, according to Thorsten Halling and colleagues at Heinrich-Heine-University in Düsseldorf, Germany.

The overall number of awards given by the three groups rose by 10% over the past 2 years. In 2021, 40% of awards given by the ACR went to females, compared with 48% by EULAR, and 50% by the BSR. However, the most prestigious prizes awarded by these groups were given less often to women, according to the researchers, who published their results online July 27, 2022, in The Lancet Rheumatology. They noted that during 2017-2021, just one in five top prizes from ACR went to a woman; once (20%) for the Presidential Gold Medal, and 26 times (23%) for the ACR Master Designation. During the same time period, only one woman (11%) received the EULAR Meritorious Service Award. In 2022, the EULAR Health Professionals in Rheumatology Lifetime Achievement Award was inaugurated and given to Christina Opava. As for the most important prizes of the BSR, the corresponding numbers for female recipients are 25% for the Michael Mason Award and 33% for the Garrod Award.” This pattern did not seem to change in 2022 at the BSR and EULAR annual meetings; the 2022 ACR annual meeting is in November.

ptasha/Getty Images

The trend is also seen in others fields, noted the researchers, who cited only one woman winning mathematics’ Fields Medal since it began in 1936 and female scientists winning only 7% of the Nobel Prize awards in the categories physiology or medicine, physics, and chemistry. In one larger study of 141 international research prizes that were awarded 3,445 times during 2001-2020, only 262 recipients were women.

Changing the status quo begins with awareness, according to the authors, who propose three strategies for prize juries to follow to raise the number of female awardees. “First, it is important to stimulate diversity among both nominees and the members of prize committees. Efforts to diversify the pool of nominees have already been initiated by large science prize players, such as the Royal Academy of Sciences in Sweden and the Wolf Foundation in Israel. This diversity should not only take gender into account, but also geographical region, ethnicity, and age. In the prize statutes, we recommend that the biological age of the applicants should no longer play a role for young scientist awards, but only the academic age. Second, if prizes are to be named after a person or people, we suggest that they should increasingly honor rheumatologists who are women to further increase their visibility in the field of rheumatology. We can note that, so far, no single award is named after a rheumatologist who is a woman. Third, we are convinced that more transparency around the nomination procedure will promote gender equity among the future prize winners.”

The authors had no conflicts of interest to declare.

The Food and Drug Administration has approved belimumab (Benlysta) for treating active lupus nephritis (LN) in children aged 5-17 years. The drug can now be used to treat adult and pediatric patients with systemic lupus erythematosus (SLE) and LN. The decision expands therapeutic options for the estimated 1.5 million Americans currently living with lupus.

“This approval marks a significant step forward in providing treatment options to these children at risk of incurring kidney damage early on in life,” Stevan W. Gibson, president and CEO of the Lupus Foundation of America, said in a press release issued by the manufacturer, GlaxoSmithKline. LN is a condition that sometimes develops in people with lupus. In LN, the autoimmune cells produced by the disease attack the kidney. Roughly 40% of people with SLE experience LN.

Olivier Le Moal/Getty Images

Damage to the kidneys causes the body to have difficulty processing waste and toxins. This can create a host of problems, including end-stage kidney disease, which may be treated only with dialysis or kidney transplant. These situations significantly increase mortality among people with lupus, especially children.

Prior to the approval, the only treatment pathway for children with active LN included immunosuppressants and corticosteroids. While they may be effective, use of these classes of drugs may come with many side effects, including susceptibility to other diseases and infections. Belimumab, by contrast, is a B-lymphocyte stimulator protein inhibitor. It inhibits the survival of B cells, which are thought to play a role in the disease’s pathophysiology.

Belimumab was first approved to treat patients with SLE in 2011. It was approved for children with SLE 8 years later. The drug’s indications were expanded to include adults with LN in 2020.

Organizations within the lupus research community have communicated their support of the FDA’s decision. “Our community has much to celebrate with the approval of the first and much-needed treatment for children with lupus nephritis,” Lupus Research Alliance President and CEO Kenneth M. Farber said in a release from the organization.

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

The Food and Drug Administration has approved belimumab (Benlysta) for treating active lupus nephritis (LN) in children aged 5-17 years. The drug can now be used to treat adult and pediatric patients with systemic lupus erythematosus (SLE) and LN. The decision expands therapeutic options for the estimated 1.5 million Americans currently living with lupus.

“This approval marks a significant step forward in providing treatment options to these children at risk of incurring kidney damage early on in life,” Stevan W. Gibson, president and CEO of the Lupus Foundation of America, said in a press release issued by the manufacturer, GlaxoSmithKline. LN is a condition that sometimes develops in people with lupus. In LN, the autoimmune cells produced by the disease attack the kidney. Roughly 40% of people with SLE experience LN.

Olivier Le Moal/Getty Images

Damage to the kidneys causes the body to have difficulty processing waste and toxins. This can create a host of problems, including end-stage kidney disease, which may be treated only with dialysis or kidney transplant. These situations significantly increase mortality among people with lupus, especially children.

Prior to the approval, the only treatment pathway for children with active LN included immunosuppressants and corticosteroids. While they may be effective, use of these classes of drugs may come with many side effects, including susceptibility to other diseases and infections. Belimumab, by contrast, is a B-lymphocyte stimulator protein inhibitor. It inhibits the survival of B cells, which are thought to play a role in the disease’s pathophysiology.

Belimumab was first approved to treat patients with SLE in 2011. It was approved for children with SLE 8 years later. The drug’s indications were expanded to include adults with LN in 2020.

Organizations within the lupus research community have communicated their support of the FDA’s decision. “Our community has much to celebrate with the approval of the first and much-needed treatment for children with lupus nephritis,” Lupus Research Alliance President and CEO Kenneth M. Farber said in a release from the organization.

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

The Food and Drug Administration has approved belimumab (Benlysta) for treating active lupus nephritis (LN) in children aged 5-17 years. The drug can now be used to treat adult and pediatric patients with systemic lupus erythematosus (SLE) and LN. The decision expands therapeutic options for the estimated 1.5 million Americans currently living with lupus.

“This approval marks a significant step forward in providing treatment options to these children at risk of incurring kidney damage early on in life,” Stevan W. Gibson, president and CEO of the Lupus Foundation of America, said in a press release issued by the manufacturer, GlaxoSmithKline. LN is a condition that sometimes develops in people with lupus. In LN, the autoimmune cells produced by the disease attack the kidney. Roughly 40% of people with SLE experience LN.

Olivier Le Moal/Getty Images

Damage to the kidneys causes the body to have difficulty processing waste and toxins. This can create a host of problems, including end-stage kidney disease, which may be treated only with dialysis or kidney transplant. These situations significantly increase mortality among people with lupus, especially children.

Prior to the approval, the only treatment pathway for children with active LN included immunosuppressants and corticosteroids. While they may be effective, use of these classes of drugs may come with many side effects, including susceptibility to other diseases and infections. Belimumab, by contrast, is a B-lymphocyte stimulator protein inhibitor. It inhibits the survival of B cells, which are thought to play a role in the disease’s pathophysiology.

Belimumab was first approved to treat patients with SLE in 2011. It was approved for children with SLE 8 years later. The drug’s indications were expanded to include adults with LN in 2020.

Organizations within the lupus research community have communicated their support of the FDA’s decision. “Our community has much to celebrate with the approval of the first and much-needed treatment for children with lupus nephritis,” Lupus Research Alliance President and CEO Kenneth M. Farber said in a release from the organization.

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

Women with well-controlled rheumatoid arthritis who used a tumor necrosis factor (TNF) inhibitor during pregnancy gave birth to infants with higher birth weight than did other patients, without an increased risk of adverse outcomes, according to findings from a Dutch prospective cohort study published online in Annals of the Rheumatic Diseases.

The study involved 188 patients drawn from the ongoing Preconceptional Counseling in Active RA (PreCARA) study, which followed patients with inflammatory rheumatic diseases before and during pregnancy. Women enrolled in PreCARA were closely monitored and treated with a therapeutic approach that aimed to achieve minimal disease activity, which included the use of TNF inhibitors.

digitalskillet/Thinkstock

Much research on TNF inhibitors during pregnancy has been limited to the first trimester and focused primarily on congenital malformations. In addition, most previous studies evaluating TNF inhibitors during pregnancy involved patients with different underlying diseases, making it difficult to interpret the results.

Hieronymus T. W. Smeele, MD, and colleagues at Erasmus University Medical Center, Rotterdam, the Netherlands, evaluated participants every 3 months before pregnancy; then again in the first, second, and third trimesters; and at 6, 12, and 26 weeks post partum. At these visits, in addition to undergoing an examination of their joints, patients completed questionnaires and gave blood samples. Disease activity was determined using the Disease Activity Score in 28 joints. Twin births and diagnoses other than RA were excluded.
 

Bigger babies

The study found that use of TNF inhibitors during pregnancy (n = 92 women) did not increase the risk of birth defects or emergency cesarean sections. While RA is typically associated with small-for-gestational-age (SGA) birth weights, TNF inhibitors were associated with a significant increase in birth weight and fewer infants born SGA, even when the comparison was adjusted for confounders, such as disease activity. At the same time, TNF inhibitors were not associated with high birth weight or with infants who were large for gestational age (LGA).

The results showed that the effects were greatest when TNF inhibitors were used in the third trimester. However, teasing out the effects based on trimester is difficult because participants who used TNF inhibitors during the third trimester were likely to use them in the first and second trimester as well. The study’s authors pointed out that these results need to be replicated.

“The immune system is not only important in the pathogenesis of RA,” the study’s authors wrote, “but also for ensuring and maintaining a normal pregnancy.” They pointed out that many adverse outcomes of pregnancy that are thought to arise from inadequate development of the placenta, such as intrauterine growth restriction, SGA, and hypertensive disorders of pregnancy, can involve an increase in proinflammatory cytokines, such as TNF. “It is tempting to speculate that treatment with [TNF inhibitors] during pregnancy promotes placentation and thereby fetal growth and birth weight by changing the balance between proinflammatory and anti-inflammatory cytokines and by increasing the number and function of [regulatory T cells].” They also hypothesize that treatment with TNF inhibitors induces epigenetic changes in the fetus, which positively influence fetal growth. 
 

Welcomed data

This is a well-done, interesting study that will add to the still-slim body of research on pregnancy in rheumatic diseases, Kevin Byram, MD, assistant professor of medicine in the division of rheumatology and immunology and associate director of the rheumatology training program at Vanderbilt University, Nashville, Tenn., told this news organization.

“Historically, pregnant women have been excluded from clinical trials, not just in rheumatoid arthritis, but in other rheumatic diseases, so we don’t have a lot of great data,” he said, adding that the more interesting part of the study was that it showed there was no increased risk of adverse outcomes. “I’m not sure what to make of the increased birth weight. It will be interesting to see if the hypothesis that there might be a role for this molecule in preventing low birth weight goes anywhere.”

The work was supported by the Dutch Arthritis Foundation. PreCARA is an investigator-initiated study that was financially supported by UCB. The authors declared no competing interests.

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

Women with well-controlled rheumatoid arthritis who used a tumor necrosis factor (TNF) inhibitor during pregnancy gave birth to infants with higher birth weight than did other patients, without an increased risk of adverse outcomes, according to findings from a Dutch prospective cohort study published online in Annals of the Rheumatic Diseases.

The study involved 188 patients drawn from the ongoing Preconceptional Counseling in Active RA (PreCARA) study, which followed patients with inflammatory rheumatic diseases before and during pregnancy. Women enrolled in PreCARA were closely monitored and treated with a therapeutic approach that aimed to achieve minimal disease activity, which included the use of TNF inhibitors.

digitalskillet/Thinkstock

Much research on TNF inhibitors during pregnancy has been limited to the first trimester and focused primarily on congenital malformations. In addition, most previous studies evaluating TNF inhibitors during pregnancy involved patients with different underlying diseases, making it difficult to interpret the results.

Hieronymus T. W. Smeele, MD, and colleagues at Erasmus University Medical Center, Rotterdam, the Netherlands, evaluated participants every 3 months before pregnancy; then again in the first, second, and third trimesters; and at 6, 12, and 26 weeks post partum. At these visits, in addition to undergoing an examination of their joints, patients completed questionnaires and gave blood samples. Disease activity was determined using the Disease Activity Score in 28 joints. Twin births and diagnoses other than RA were excluded.
 

Bigger babies

The study found that use of TNF inhibitors during pregnancy (n = 92 women) did not increase the risk of birth defects or emergency cesarean sections. While RA is typically associated with small-for-gestational-age (SGA) birth weights, TNF inhibitors were associated with a significant increase in birth weight and fewer infants born SGA, even when the comparison was adjusted for confounders, such as disease activity. At the same time, TNF inhibitors were not associated with high birth weight or with infants who were large for gestational age (LGA).

The results showed that the effects were greatest when TNF inhibitors were used in the third trimester. However, teasing out the effects based on trimester is difficult because participants who used TNF inhibitors during the third trimester were likely to use them in the first and second trimester as well. The study’s authors pointed out that these results need to be replicated.

“The immune system is not only important in the pathogenesis of RA,” the study’s authors wrote, “but also for ensuring and maintaining a normal pregnancy.” They pointed out that many adverse outcomes of pregnancy that are thought to arise from inadequate development of the placenta, such as intrauterine growth restriction, SGA, and hypertensive disorders of pregnancy, can involve an increase in proinflammatory cytokines, such as TNF. “It is tempting to speculate that treatment with [TNF inhibitors] during pregnancy promotes placentation and thereby fetal growth and birth weight by changing the balance between proinflammatory and anti-inflammatory cytokines and by increasing the number and function of [regulatory T cells].” They also hypothesize that treatment with TNF inhibitors induces epigenetic changes in the fetus, which positively influence fetal growth. 
 

Welcomed data

This is a well-done, interesting study that will add to the still-slim body of research on pregnancy in rheumatic diseases, Kevin Byram, MD, assistant professor of medicine in the division of rheumatology and immunology and associate director of the rheumatology training program at Vanderbilt University, Nashville, Tenn., told this news organization.

“Historically, pregnant women have been excluded from clinical trials, not just in rheumatoid arthritis, but in other rheumatic diseases, so we don’t have a lot of great data,” he said, adding that the more interesting part of the study was that it showed there was no increased risk of adverse outcomes. “I’m not sure what to make of the increased birth weight. It will be interesting to see if the hypothesis that there might be a role for this molecule in preventing low birth weight goes anywhere.”

The work was supported by the Dutch Arthritis Foundation. PreCARA is an investigator-initiated study that was financially supported by UCB. The authors declared no competing interests.

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

Women with well-controlled rheumatoid arthritis who used a tumor necrosis factor (TNF) inhibitor during pregnancy gave birth to infants with higher birth weight than did other patients, without an increased risk of adverse outcomes, according to findings from a Dutch prospective cohort study published online in Annals of the Rheumatic Diseases.

The study involved 188 patients drawn from the ongoing Preconceptional Counseling in Active RA (PreCARA) study, which followed patients with inflammatory rheumatic diseases before and during pregnancy. Women enrolled in PreCARA were closely monitored and treated with a therapeutic approach that aimed to achieve minimal disease activity, which included the use of TNF inhibitors.

digitalskillet/Thinkstock

Much research on TNF inhibitors during pregnancy has been limited to the first trimester and focused primarily on congenital malformations. In addition, most previous studies evaluating TNF inhibitors during pregnancy involved patients with different underlying diseases, making it difficult to interpret the results.

Hieronymus T. W. Smeele, MD, and colleagues at Erasmus University Medical Center, Rotterdam, the Netherlands, evaluated participants every 3 months before pregnancy; then again in the first, second, and third trimesters; and at 6, 12, and 26 weeks post partum. At these visits, in addition to undergoing an examination of their joints, patients completed questionnaires and gave blood samples. Disease activity was determined using the Disease Activity Score in 28 joints. Twin births and diagnoses other than RA were excluded.
 

Bigger babies

The study found that use of TNF inhibitors during pregnancy (n = 92 women) did not increase the risk of birth defects or emergency cesarean sections. While RA is typically associated with small-for-gestational-age (SGA) birth weights, TNF inhibitors were associated with a significant increase in birth weight and fewer infants born SGA, even when the comparison was adjusted for confounders, such as disease activity. At the same time, TNF inhibitors were not associated with high birth weight or with infants who were large for gestational age (LGA).

The results showed that the effects were greatest when TNF inhibitors were used in the third trimester. However, teasing out the effects based on trimester is difficult because participants who used TNF inhibitors during the third trimester were likely to use them in the first and second trimester as well. The study’s authors pointed out that these results need to be replicated.

“The immune system is not only important in the pathogenesis of RA,” the study’s authors wrote, “but also for ensuring and maintaining a normal pregnancy.” They pointed out that many adverse outcomes of pregnancy that are thought to arise from inadequate development of the placenta, such as intrauterine growth restriction, SGA, and hypertensive disorders of pregnancy, can involve an increase in proinflammatory cytokines, such as TNF. “It is tempting to speculate that treatment with [TNF inhibitors] during pregnancy promotes placentation and thereby fetal growth and birth weight by changing the balance between proinflammatory and anti-inflammatory cytokines and by increasing the number and function of [regulatory T cells].” They also hypothesize that treatment with TNF inhibitors induces epigenetic changes in the fetus, which positively influence fetal growth. 
 

Welcomed data

This is a well-done, interesting study that will add to the still-slim body of research on pregnancy in rheumatic diseases, Kevin Byram, MD, assistant professor of medicine in the division of rheumatology and immunology and associate director of the rheumatology training program at Vanderbilt University, Nashville, Tenn., told this news organization.

“Historically, pregnant women have been excluded from clinical trials, not just in rheumatoid arthritis, but in other rheumatic diseases, so we don’t have a lot of great data,” he said, adding that the more interesting part of the study was that it showed there was no increased risk of adverse outcomes. “I’m not sure what to make of the increased birth weight. It will be interesting to see if the hypothesis that there might be a role for this molecule in preventing low birth weight goes anywhere.”

The work was supported by the Dutch Arthritis Foundation. PreCARA is an investigator-initiated study that was financially supported by UCB. The authors declared no competing interests.

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