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Burnout and stress of today: How do we cope?

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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.

Dr. Douglas S. Paauw

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.

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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.

Dr. Douglas S. Paauw

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.

Dr. Douglas S. Paauw

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.

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Gout flares linked to transient jump in MI, stroke risk

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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.

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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.

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Ustekinumab becomes second biologic approved for PsA in kids

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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.

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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.

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Commentary: Concomitant Lung Disease, Drug Efficacy, and Potential Misdiagnosis in RA, August 2022

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Dr. Jayatilleke scans the journals, so you don't have to!

Arundathi Jayatilleke, MD

Interstitial lung disease (ILD) is a serious and not infrequent complication of rheumatoid arthritis (RA). Despite the use of several immunosuppressive medications for ILD as well as others for RA, the most effective treatment for both is yet unclear. Prior cross-sectional, retrospective, and open-label registry studies have suggested that abatacept can be used in patients with RA-ILD, with stability or improvement in pulmonary parameters in a majority of patients. Mena-Vazquez and colleagues present the results of a prospective, observational cohort study with 57 patients from multiple centers in Spain. Similar to previously published results, this study found stability or improvement in pulmonary function tests in 70% of patients as well as improvement in RA disease activity. A relatively high proportion of patients (25 in 57) experienced infections. The study lends further weight to the proposal that abatacept is a reasonable choice in patients with RA-ILD for treatment of both joint and pulmonary inflammation, given the lack of randomized controlled trials.

 

Lauper and colleagues published the results of a large cohort study of more than 30,000 treatment courses in patients with RA, looking at the efficacy of different biologics and a Janus kinase (JAK) inhibitor. Discontinuation of therapy was used as the primary efficacy outcome, and one secondary outcome was low disease activity based on Clinical Disease Activity Index (CDAI) at 12 months. Over 17,000 courses were anti–tumor necrosis factor (TNF) therapy, with about 7000 JAK-inhibitor therapy courses and the remainder an interleukin 6 (IL-6) inhibitor or abatacept therapy; individual data was only available from 13 to 17 registries (depending on the parameter of interest). Overall, IL-6 inhibitors and JAK inhibitors were less frequently stopped for ineffectiveness compared with anti-TNF agents, but were more frequently stopped owing to adverse events. Drug retention rates also varied between different countries, suggesting that prescription pattern differences may affect the primary outcome. In terms of CDAI, response rates at 1 year were similar between anti-TNF agents, JAK inhibitors, and IL-6 inhibitors and was slightly lower for abatacept. This real-world study does support similar efficacy between these classes of medications, though further conclusions are somewhat hampered by the lack of individual data.

 

A study in Japan by Mori and colleagues looked at biologic disease-modifying antirheumatic drugs (bDMARD) (TNF inhibitors and an IL-6 inhibitor) and tofacitinib discontinuation in a cohort of 97 patients with RA . Patients were required to initially be in a high or moderate disease activity state prior to treatment, then in remission or a low disease activity state with treatment for more than 48 weeks. Mean follow-up was 2.1 years and disease flare occurred in about 75% of patients at about 1.6 years after medication discontinuation. Though bDMARD- or targeted synthetic DMARD (tsDMARD)–free remission was not "durable" for most patients, the majority of those patients who experienced flares improved with resumption of their previous medication. Though it is reassuring that most study patients were able to discontinue their bDMARD or tsDMARD medication for a period of time, the fact that most experienced flares within 2 years suggests that discontinuation of these medications in patients with high disease activity is not a viable long-term approach.

 

Krekeler and colleagues performed a retrospective analysis of about 500 patients seen in a single rheumatology clinic to evaluate possible misdiagnosis of RA. The diagnosis of calcium pyrophosphate deposition disease (CPPD), as well as the presence of radiographic chondrocalcinosis, were more frequently found among patients diagnosed with seronegative RA vs those diagnosed with seropositive RA, particularly RA in the wrists. The CPPD diagnosis was made by rheumatologists on the basis of the presence of radiographic chondrocalcinosis along with typical joint swelling and signs of inflammation. Because chondrocalcinosis was part of the CPPD diagnosis, it is unsurprising that both followed similar patterns. Whether patients with CPPD were actually misdiagnosed as having seronegative RA is unclear from this retrospective study; as the authors note, chondrocalcinosis itself has been found to be associated with older age and osteoarthritis in prior studies, particularly in the knee. However, the study confirms that alternative diagnoses in seronegative RA should be considered.

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Lewis Katz School of Medicine, Temple University

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Dr. Jayatilleke scans the journals, so you don't have to!
Dr. Jayatilleke scans the journals, so you don't have to!

Arundathi Jayatilleke, MD

Interstitial lung disease (ILD) is a serious and not infrequent complication of rheumatoid arthritis (RA). Despite the use of several immunosuppressive medications for ILD as well as others for RA, the most effective treatment for both is yet unclear. Prior cross-sectional, retrospective, and open-label registry studies have suggested that abatacept can be used in patients with RA-ILD, with stability or improvement in pulmonary parameters in a majority of patients. Mena-Vazquez and colleagues present the results of a prospective, observational cohort study with 57 patients from multiple centers in Spain. Similar to previously published results, this study found stability or improvement in pulmonary function tests in 70% of patients as well as improvement in RA disease activity. A relatively high proportion of patients (25 in 57) experienced infections. The study lends further weight to the proposal that abatacept is a reasonable choice in patients with RA-ILD for treatment of both joint and pulmonary inflammation, given the lack of randomized controlled trials.

 

Lauper and colleagues published the results of a large cohort study of more than 30,000 treatment courses in patients with RA, looking at the efficacy of different biologics and a Janus kinase (JAK) inhibitor. Discontinuation of therapy was used as the primary efficacy outcome, and one secondary outcome was low disease activity based on Clinical Disease Activity Index (CDAI) at 12 months. Over 17,000 courses were anti–tumor necrosis factor (TNF) therapy, with about 7000 JAK-inhibitor therapy courses and the remainder an interleukin 6 (IL-6) inhibitor or abatacept therapy; individual data was only available from 13 to 17 registries (depending on the parameter of interest). Overall, IL-6 inhibitors and JAK inhibitors were less frequently stopped for ineffectiveness compared with anti-TNF agents, but were more frequently stopped owing to adverse events. Drug retention rates also varied between different countries, suggesting that prescription pattern differences may affect the primary outcome. In terms of CDAI, response rates at 1 year were similar between anti-TNF agents, JAK inhibitors, and IL-6 inhibitors and was slightly lower for abatacept. This real-world study does support similar efficacy between these classes of medications, though further conclusions are somewhat hampered by the lack of individual data.

 

A study in Japan by Mori and colleagues looked at biologic disease-modifying antirheumatic drugs (bDMARD) (TNF inhibitors and an IL-6 inhibitor) and tofacitinib discontinuation in a cohort of 97 patients with RA . Patients were required to initially be in a high or moderate disease activity state prior to treatment, then in remission or a low disease activity state with treatment for more than 48 weeks. Mean follow-up was 2.1 years and disease flare occurred in about 75% of patients at about 1.6 years after medication discontinuation. Though bDMARD- or targeted synthetic DMARD (tsDMARD)–free remission was not "durable" for most patients, the majority of those patients who experienced flares improved with resumption of their previous medication. Though it is reassuring that most study patients were able to discontinue their bDMARD or tsDMARD medication for a period of time, the fact that most experienced flares within 2 years suggests that discontinuation of these medications in patients with high disease activity is not a viable long-term approach.

 

Krekeler and colleagues performed a retrospective analysis of about 500 patients seen in a single rheumatology clinic to evaluate possible misdiagnosis of RA. The diagnosis of calcium pyrophosphate deposition disease (CPPD), as well as the presence of radiographic chondrocalcinosis, were more frequently found among patients diagnosed with seronegative RA vs those diagnosed with seropositive RA, particularly RA in the wrists. The CPPD diagnosis was made by rheumatologists on the basis of the presence of radiographic chondrocalcinosis along with typical joint swelling and signs of inflammation. Because chondrocalcinosis was part of the CPPD diagnosis, it is unsurprising that both followed similar patterns. Whether patients with CPPD were actually misdiagnosed as having seronegative RA is unclear from this retrospective study; as the authors note, chondrocalcinosis itself has been found to be associated with older age and osteoarthritis in prior studies, particularly in the knee. However, the study confirms that alternative diagnoses in seronegative RA should be considered.

Arundathi Jayatilleke, MD

Interstitial lung disease (ILD) is a serious and not infrequent complication of rheumatoid arthritis (RA). Despite the use of several immunosuppressive medications for ILD as well as others for RA, the most effective treatment for both is yet unclear. Prior cross-sectional, retrospective, and open-label registry studies have suggested that abatacept can be used in patients with RA-ILD, with stability or improvement in pulmonary parameters in a majority of patients. Mena-Vazquez and colleagues present the results of a prospective, observational cohort study with 57 patients from multiple centers in Spain. Similar to previously published results, this study found stability or improvement in pulmonary function tests in 70% of patients as well as improvement in RA disease activity. A relatively high proportion of patients (25 in 57) experienced infections. The study lends further weight to the proposal that abatacept is a reasonable choice in patients with RA-ILD for treatment of both joint and pulmonary inflammation, given the lack of randomized controlled trials.

 

Lauper and colleagues published the results of a large cohort study of more than 30,000 treatment courses in patients with RA, looking at the efficacy of different biologics and a Janus kinase (JAK) inhibitor. Discontinuation of therapy was used as the primary efficacy outcome, and one secondary outcome was low disease activity based on Clinical Disease Activity Index (CDAI) at 12 months. Over 17,000 courses were anti–tumor necrosis factor (TNF) therapy, with about 7000 JAK-inhibitor therapy courses and the remainder an interleukin 6 (IL-6) inhibitor or abatacept therapy; individual data was only available from 13 to 17 registries (depending on the parameter of interest). Overall, IL-6 inhibitors and JAK inhibitors were less frequently stopped for ineffectiveness compared with anti-TNF agents, but were more frequently stopped owing to adverse events. Drug retention rates also varied between different countries, suggesting that prescription pattern differences may affect the primary outcome. In terms of CDAI, response rates at 1 year were similar between anti-TNF agents, JAK inhibitors, and IL-6 inhibitors and was slightly lower for abatacept. This real-world study does support similar efficacy between these classes of medications, though further conclusions are somewhat hampered by the lack of individual data.

 

A study in Japan by Mori and colleagues looked at biologic disease-modifying antirheumatic drugs (bDMARD) (TNF inhibitors and an IL-6 inhibitor) and tofacitinib discontinuation in a cohort of 97 patients with RA . Patients were required to initially be in a high or moderate disease activity state prior to treatment, then in remission or a low disease activity state with treatment for more than 48 weeks. Mean follow-up was 2.1 years and disease flare occurred in about 75% of patients at about 1.6 years after medication discontinuation. Though bDMARD- or targeted synthetic DMARD (tsDMARD)–free remission was not "durable" for most patients, the majority of those patients who experienced flares improved with resumption of their previous medication. Though it is reassuring that most study patients were able to discontinue their bDMARD or tsDMARD medication for a period of time, the fact that most experienced flares within 2 years suggests that discontinuation of these medications in patients with high disease activity is not a viable long-term approach.

 

Krekeler and colleagues performed a retrospective analysis of about 500 patients seen in a single rheumatology clinic to evaluate possible misdiagnosis of RA. The diagnosis of calcium pyrophosphate deposition disease (CPPD), as well as the presence of radiographic chondrocalcinosis, were more frequently found among patients diagnosed with seronegative RA vs those diagnosed with seropositive RA, particularly RA in the wrists. The CPPD diagnosis was made by rheumatologists on the basis of the presence of radiographic chondrocalcinosis along with typical joint swelling and signs of inflammation. Because chondrocalcinosis was part of the CPPD diagnosis, it is unsurprising that both followed similar patterns. Whether patients with CPPD were actually misdiagnosed as having seronegative RA is unclear from this retrospective study; as the authors note, chondrocalcinosis itself has been found to be associated with older age and osteoarthritis in prior studies, particularly in the knee. However, the study confirms that alternative diagnoses in seronegative RA should be considered.

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Commentary: Exercise, Mental Health, and Checkpoint Inhibitors in PsA, August 2022

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Vinod Chandran, MBBS, MD, DM, PhD

Biomechanical stress and trauma are important factors driving the development and progression of psoriatic arthritis (PsA). On the other hand, physical exercise is beneficial for patients with arthritis. However, there is concern that high-intensity interval training (HIIT) may worsen PsA. Hypothesizing that bone marrow edema changes could occur in patients with PsA after HIIT despite no reported changes in disease activity by clinical examination, Chronaiou and colleagues aimed to assess whether HIIT in PsA patients led to MRI-detectable changes in the axial skeleton. Comparing 19 PsA patients who went through 11 weeks of HIIT with 20 patients who had no change in physical exercise habits, they found no significant changes in bone marrow edema on MRI images of the spine after HIIT. Thus, the 11-week HIIT regimen may be safe in PsA.

 

Mental health problems are often underestimated in psoriatic disease. Lada and colleagues aimed to estimate the prevalence of depression in patients with psoriatic disease and determine whether PsA is associated with higher depression and anxiety in patients with psoriasis. Analyzing data from British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR) participants (540 with psoriasis and 167 with both psoriasis and PsA) who had completed the Hospital Anxiety and Depression Scale (HADS), they found that the prevalence of depression was higher in patients with PsA (32%) than in patients without PsA (22.7%) using a HADS cutoff of 8 (odds ratio 1.66; 95% CI 1.13--2.43). Pain mediated the effect of PsA on depression and anxiety.

 

Inhibitors of interleukin (IL)-23 are safe and efficacious in the treatment of psoriasis and PsA. However, changes in composite PsA indices have not been investigated in detail. Using pooled data from the phase 3 DISCOVER-1 (n = 381) and DISCOVER-2 (n = 739) studies, Coates and colleagues demonstrated that a significantly higher proportion of patients receiving guselkumab every 4 or 8 weeks vs placebo achieved low disease activity according to the Disease Activity Index for PsA (DAPSA) at week 8 (19.8%/17.3% vs 8.1%), DAPSA remission at week 12 (4.3%/4.3% vs 0.5%), minimal disease activity at week 16 (14.7%/16.5% vs 4.6%; all P < .001), and very low disease activity at week 24 (6.4%/4.3% vs 1.3%; P < .05), with improvements maintained until week 52. Thus, compared with placebo, treatment with guselkumab leads to early and sustained benefits for patients with PsA.

Similarly, Ostor and colleagues demonstrated in the phase 3 KEEPsAKE2 trial, which included 443 patients with PsA, that, at week 24, patients receiving risankizumab report a significantly greater improvement in the mean pain index score (-14.7 vs -6.5; P < .001), fatigue score (4.9 vs 2.6; P < .01), patient's global assessment of disease activity (-16.5 vs -7.7; P < .001), general health status (0.09 vs 0.01; P < .001), and physical functioning (5.1 vs 2.0; P < .001) compared with placebo.

 

In another study, treatment with bimekizumab, an inhibitor of IL-17A and IL-17F, was associated with sustained improvement in patient-reported outcomes. Mease and colleagues report that, at week 48, there was a substantial improvement in mean arthritis pain (29.9 points), fatigue (2.4 points), Health Assessment Questionnaire-Disability Index (0.43 points), and Physical Component Summary score (9.1 points), with improvements sustained till week 152. High proportions of patients achieved the Patient Acceptable Symptom State at weeks 48 (75.2%) and 152 (65.0%). Thus, inhibitors of IL-23 and IL-17 have established efficacy in the treatment of PsA.

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Vinod Chandran, MBBS, MD, DM, PhD, Associate Professor, Department of Medicine, University of Toledo, Toronto, Ontario, Canada

Vinod Chandran, MBBS, MD, DM, PhD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Amgen; Bristol-Myers Squibb; Eli Lilly; Janssen; Novartis; Pfizer; UCB

Received research grant from: Amgen; AbbVie; Eli Lilly

Spousal employment: Eli Lilly; AstraZeneca

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Vinod Chandran, MBBS, MD, DM, PhD, Associate Professor, Department of Medicine, University of Toledo, Toronto, Ontario, Canada

Vinod Chandran, MBBS, MD, DM, PhD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Amgen; Bristol-Myers Squibb; Eli Lilly; Janssen; Novartis; Pfizer; UCB

Received research grant from: Amgen; AbbVie; Eli Lilly

Spousal employment: Eli Lilly; AstraZeneca

Author and Disclosure Information

Vinod Chandran, MBBS, MD, DM, PhD, Associate Professor, Department of Medicine, University of Toledo, Toronto, Ontario, Canada

Vinod Chandran, MBBS, MD, DM, PhD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AbbVie; Amgen; Bristol-Myers Squibb; Eli Lilly; Janssen; Novartis; Pfizer; UCB

Received research grant from: Amgen; AbbVie; Eli Lilly

Spousal employment: Eli Lilly; AstraZeneca

Dr. Chandran scans the journals, so you don't have to!
Dr. Chandran scans the journals, so you don't have to!

Vinod Chandran, MBBS, MD, DM, PhD

Biomechanical stress and trauma are important factors driving the development and progression of psoriatic arthritis (PsA). On the other hand, physical exercise is beneficial for patients with arthritis. However, there is concern that high-intensity interval training (HIIT) may worsen PsA. Hypothesizing that bone marrow edema changes could occur in patients with PsA after HIIT despite no reported changes in disease activity by clinical examination, Chronaiou and colleagues aimed to assess whether HIIT in PsA patients led to MRI-detectable changes in the axial skeleton. Comparing 19 PsA patients who went through 11 weeks of HIIT with 20 patients who had no change in physical exercise habits, they found no significant changes in bone marrow edema on MRI images of the spine after HIIT. Thus, the 11-week HIIT regimen may be safe in PsA.

 

Mental health problems are often underestimated in psoriatic disease. Lada and colleagues aimed to estimate the prevalence of depression in patients with psoriatic disease and determine whether PsA is associated with higher depression and anxiety in patients with psoriasis. Analyzing data from British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR) participants (540 with psoriasis and 167 with both psoriasis and PsA) who had completed the Hospital Anxiety and Depression Scale (HADS), they found that the prevalence of depression was higher in patients with PsA (32%) than in patients without PsA (22.7%) using a HADS cutoff of 8 (odds ratio 1.66; 95% CI 1.13--2.43). Pain mediated the effect of PsA on depression and anxiety.

 

Inhibitors of interleukin (IL)-23 are safe and efficacious in the treatment of psoriasis and PsA. However, changes in composite PsA indices have not been investigated in detail. Using pooled data from the phase 3 DISCOVER-1 (n = 381) and DISCOVER-2 (n = 739) studies, Coates and colleagues demonstrated that a significantly higher proportion of patients receiving guselkumab every 4 or 8 weeks vs placebo achieved low disease activity according to the Disease Activity Index for PsA (DAPSA) at week 8 (19.8%/17.3% vs 8.1%), DAPSA remission at week 12 (4.3%/4.3% vs 0.5%), minimal disease activity at week 16 (14.7%/16.5% vs 4.6%; all P < .001), and very low disease activity at week 24 (6.4%/4.3% vs 1.3%; P < .05), with improvements maintained until week 52. Thus, compared with placebo, treatment with guselkumab leads to early and sustained benefits for patients with PsA.

Similarly, Ostor and colleagues demonstrated in the phase 3 KEEPsAKE2 trial, which included 443 patients with PsA, that, at week 24, patients receiving risankizumab report a significantly greater improvement in the mean pain index score (-14.7 vs -6.5; P < .001), fatigue score (4.9 vs 2.6; P < .01), patient's global assessment of disease activity (-16.5 vs -7.7; P < .001), general health status (0.09 vs 0.01; P < .001), and physical functioning (5.1 vs 2.0; P < .001) compared with placebo.

 

In another study, treatment with bimekizumab, an inhibitor of IL-17A and IL-17F, was associated with sustained improvement in patient-reported outcomes. Mease and colleagues report that, at week 48, there was a substantial improvement in mean arthritis pain (29.9 points), fatigue (2.4 points), Health Assessment Questionnaire-Disability Index (0.43 points), and Physical Component Summary score (9.1 points), with improvements sustained till week 152. High proportions of patients achieved the Patient Acceptable Symptom State at weeks 48 (75.2%) and 152 (65.0%). Thus, inhibitors of IL-23 and IL-17 have established efficacy in the treatment of PsA.

Vinod Chandran, MBBS, MD, DM, PhD

Biomechanical stress and trauma are important factors driving the development and progression of psoriatic arthritis (PsA). On the other hand, physical exercise is beneficial for patients with arthritis. However, there is concern that high-intensity interval training (HIIT) may worsen PsA. Hypothesizing that bone marrow edema changes could occur in patients with PsA after HIIT despite no reported changes in disease activity by clinical examination, Chronaiou and colleagues aimed to assess whether HIIT in PsA patients led to MRI-detectable changes in the axial skeleton. Comparing 19 PsA patients who went through 11 weeks of HIIT with 20 patients who had no change in physical exercise habits, they found no significant changes in bone marrow edema on MRI images of the spine after HIIT. Thus, the 11-week HIIT regimen may be safe in PsA.

 

Mental health problems are often underestimated in psoriatic disease. Lada and colleagues aimed to estimate the prevalence of depression in patients with psoriatic disease and determine whether PsA is associated with higher depression and anxiety in patients with psoriasis. Analyzing data from British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR) participants (540 with psoriasis and 167 with both psoriasis and PsA) who had completed the Hospital Anxiety and Depression Scale (HADS), they found that the prevalence of depression was higher in patients with PsA (32%) than in patients without PsA (22.7%) using a HADS cutoff of 8 (odds ratio 1.66; 95% CI 1.13--2.43). Pain mediated the effect of PsA on depression and anxiety.

 

Inhibitors of interleukin (IL)-23 are safe and efficacious in the treatment of psoriasis and PsA. However, changes in composite PsA indices have not been investigated in detail. Using pooled data from the phase 3 DISCOVER-1 (n = 381) and DISCOVER-2 (n = 739) studies, Coates and colleagues demonstrated that a significantly higher proportion of patients receiving guselkumab every 4 or 8 weeks vs placebo achieved low disease activity according to the Disease Activity Index for PsA (DAPSA) at week 8 (19.8%/17.3% vs 8.1%), DAPSA remission at week 12 (4.3%/4.3% vs 0.5%), minimal disease activity at week 16 (14.7%/16.5% vs 4.6%; all P < .001), and very low disease activity at week 24 (6.4%/4.3% vs 1.3%; P < .05), with improvements maintained until week 52. Thus, compared with placebo, treatment with guselkumab leads to early and sustained benefits for patients with PsA.

Similarly, Ostor and colleagues demonstrated in the phase 3 KEEPsAKE2 trial, which included 443 patients with PsA, that, at week 24, patients receiving risankizumab report a significantly greater improvement in the mean pain index score (-14.7 vs -6.5; P < .001), fatigue score (4.9 vs 2.6; P < .01), patient's global assessment of disease activity (-16.5 vs -7.7; P < .001), general health status (0.09 vs 0.01; P < .001), and physical functioning (5.1 vs 2.0; P < .001) compared with placebo.

 

In another study, treatment with bimekizumab, an inhibitor of IL-17A and IL-17F, was associated with sustained improvement in patient-reported outcomes. Mease and colleagues report that, at week 48, there was a substantial improvement in mean arthritis pain (29.9 points), fatigue (2.4 points), Health Assessment Questionnaire-Disability Index (0.43 points), and Physical Component Summary score (9.1 points), with improvements sustained till week 152. High proportions of patients achieved the Patient Acceptable Symptom State at weeks 48 (75.2%) and 152 (65.0%). Thus, inhibitors of IL-23 and IL-17 have established efficacy in the treatment of PsA.

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COVID skin manifestations vary by type of variant, U.K. study finds

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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.

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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.

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FROM THE BRITISH JOURNAL OF DERMATOLOGY

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Evusheld for COVID-19: Lifesaving and free, but still few takers

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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.

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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.

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Topical roflumilast approved for psoriasis in adults and adolescents

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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.

Dr. Mark G. Lebwohl

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.

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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.

Dr. Mark G. Lebwohl

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.

Dr. Mark G. Lebwohl

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.

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High intensity interval training safe in PsA

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Key clinical point: The 11-week high intensity interval training (HIIT) regimen had no influence on the bone marrow edema (BME) in patients with psoriatic arthritis (PsA).

Major finding: After 11 weeks, similar proportions of patients in the HIIT and control (no changes in exercise regimen) groups had BME changes, as assessed by a radiologist (P  =  .5) and SpondyloArthritis Research Consortium of Canada scores (P  =  1). Although the values of 20 textural features were significantly different in the voxels of BME vs healthy bone marrow (P < .001), the textural features of PsA lesions were similar between the HIIT and control groups (P > .2).

Study details: Findings are from the analysis of a part of a randomized controlled trial including 37 patients with PsA who performed HIIT 3 times/week for 11 weeks or followed the control regimen and were evaluated by MRI.

Disclosures: This research was funded by Norwegian Extra Foundation for Health and Rehabilitation and Sør-Trøndelag University college. The authors declared no conflicts of interest.

Source: Chronaiou I et al. Evaluating the impact of high intensity interval training on axial psoriatic arthritis based on MR images. Diagnostics (Basel). 2022;12(6):1420 (Jun 8). Doi: 10.3390/diagnostics12061420

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Key clinical point: The 11-week high intensity interval training (HIIT) regimen had no influence on the bone marrow edema (BME) in patients with psoriatic arthritis (PsA).

Major finding: After 11 weeks, similar proportions of patients in the HIIT and control (no changes in exercise regimen) groups had BME changes, as assessed by a radiologist (P  =  .5) and SpondyloArthritis Research Consortium of Canada scores (P  =  1). Although the values of 20 textural features were significantly different in the voxels of BME vs healthy bone marrow (P < .001), the textural features of PsA lesions were similar between the HIIT and control groups (P > .2).

Study details: Findings are from the analysis of a part of a randomized controlled trial including 37 patients with PsA who performed HIIT 3 times/week for 11 weeks or followed the control regimen and were evaluated by MRI.

Disclosures: This research was funded by Norwegian Extra Foundation for Health and Rehabilitation and Sør-Trøndelag University college. The authors declared no conflicts of interest.

Source: Chronaiou I et al. Evaluating the impact of high intensity interval training on axial psoriatic arthritis based on MR images. Diagnostics (Basel). 2022;12(6):1420 (Jun 8). Doi: 10.3390/diagnostics12061420

Key clinical point: The 11-week high intensity interval training (HIIT) regimen had no influence on the bone marrow edema (BME) in patients with psoriatic arthritis (PsA).

Major finding: After 11 weeks, similar proportions of patients in the HIIT and control (no changes in exercise regimen) groups had BME changes, as assessed by a radiologist (P  =  .5) and SpondyloArthritis Research Consortium of Canada scores (P  =  1). Although the values of 20 textural features were significantly different in the voxels of BME vs healthy bone marrow (P < .001), the textural features of PsA lesions were similar between the HIIT and control groups (P > .2).

Study details: Findings are from the analysis of a part of a randomized controlled trial including 37 patients with PsA who performed HIIT 3 times/week for 11 weeks or followed the control regimen and were evaluated by MRI.

Disclosures: This research was funded by Norwegian Extra Foundation for Health and Rehabilitation and Sør-Trøndelag University college. The authors declared no conflicts of interest.

Source: Chronaiou I et al. Evaluating the impact of high intensity interval training on axial psoriatic arthritis based on MR images. Diagnostics (Basel). 2022;12(6):1420 (Jun 8). Doi: 10.3390/diagnostics12061420

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Presence of PsA increases prevalence of anxiety and depression in psoriasis

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Key clinical point: Patients with concomitant psoriasis and psoriatic arthritis (PsA) vs only psoriasis were more likely to experience mild depressive symptoms and anxiety, with the association being mediated by pain.

Major finding: Among patients with psoriasis, those with vs without PsA had a higher prevalence of mild depressive symptoms (Hospital Anxiety and Depression Scale [HADS] score ≥8: adjusted odds ratio [aOR] 1.64; P  =  .037) but not severe depressive symptoms (HADS score ≥ 11) and a high prevalence of mild-to-severe anxiety (HADS score ≥ 8: aOR 1.51; P  =  .038 and HADS score ≥ 11; aOR 1.62; P  =  .037). Pain mediated the effect of PsA on depression and anxiety.

Study details: The data of 707 British Association of Dermatologists Biologic and Immunomodulators Register participants (540 with psoriasis and 167 with both psoriasis and PsA) were analyzed.

Disclosures: This study was funded by the UK National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre. Some authors declared serving as speakers or advisory board members, or receiving honoraria, funding, compensation, research grants, or consulting fees from several sources.

Source: Lada G et al. Associations between psoriatic arthritis and mental health among patients with psoriasis: A replication and extension study using the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR). Skin Health Dis. 2022;e149 (Jul 6). Doi: 10.1002/ski2.149

 

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Key clinical point: Patients with concomitant psoriasis and psoriatic arthritis (PsA) vs only psoriasis were more likely to experience mild depressive symptoms and anxiety, with the association being mediated by pain.

Major finding: Among patients with psoriasis, those with vs without PsA had a higher prevalence of mild depressive symptoms (Hospital Anxiety and Depression Scale [HADS] score ≥8: adjusted odds ratio [aOR] 1.64; P  =  .037) but not severe depressive symptoms (HADS score ≥ 11) and a high prevalence of mild-to-severe anxiety (HADS score ≥ 8: aOR 1.51; P  =  .038 and HADS score ≥ 11; aOR 1.62; P  =  .037). Pain mediated the effect of PsA on depression and anxiety.

Study details: The data of 707 British Association of Dermatologists Biologic and Immunomodulators Register participants (540 with psoriasis and 167 with both psoriasis and PsA) were analyzed.

Disclosures: This study was funded by the UK National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre. Some authors declared serving as speakers or advisory board members, or receiving honoraria, funding, compensation, research grants, or consulting fees from several sources.

Source: Lada G et al. Associations between psoriatic arthritis and mental health among patients with psoriasis: A replication and extension study using the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR). Skin Health Dis. 2022;e149 (Jul 6). Doi: 10.1002/ski2.149

 

Key clinical point: Patients with concomitant psoriasis and psoriatic arthritis (PsA) vs only psoriasis were more likely to experience mild depressive symptoms and anxiety, with the association being mediated by pain.

Major finding: Among patients with psoriasis, those with vs without PsA had a higher prevalence of mild depressive symptoms (Hospital Anxiety and Depression Scale [HADS] score ≥8: adjusted odds ratio [aOR] 1.64; P  =  .037) but not severe depressive symptoms (HADS score ≥ 11) and a high prevalence of mild-to-severe anxiety (HADS score ≥ 8: aOR 1.51; P  =  .038 and HADS score ≥ 11; aOR 1.62; P  =  .037). Pain mediated the effect of PsA on depression and anxiety.

Study details: The data of 707 British Association of Dermatologists Biologic and Immunomodulators Register participants (540 with psoriasis and 167 with both psoriasis and PsA) were analyzed.

Disclosures: This study was funded by the UK National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre. Some authors declared serving as speakers or advisory board members, or receiving honoraria, funding, compensation, research grants, or consulting fees from several sources.

Source: Lada G et al. Associations between psoriatic arthritis and mental health among patients with psoriasis: A replication and extension study using the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR). Skin Health Dis. 2022;e149 (Jul 6). Doi: 10.1002/ski2.149

 

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Clinical Edge Journal Scan: Psoriatic Arthritis August 2022
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