Psoriasis

Tumor necrosis factor inhibitors have long been the go-to treatment of choice for patients with psoriasis and psoriatic arthritis (PsA). They’ve served patients well since etanercept was first approved for PsA in 2002, but today, with the availability of more attractive interleukin-17 and IL-23 inhibitors, dermatologists and rheumatologists are asking whether it’s time to reconsider the use of TNF inhibitors as first-line therapy in psoriasis and PsA.

“TNF inhibitors have served psoriasis patients well for many years. The question is, ‘Is it time to move on from them as first-line agents for psoriasis?’ ” said April W. Armstrong, MD, MPH, a dermatologist and associate dean for clinical research at the University of Southern California, Los Angeles. Dr. Armstrong participated in a point/counterpoint debate about the merits of IL-17 and IL-23 inhibitors over TNF inhibitors at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “For the majority of our patients, IL-17 and IL-23 inhibitors are probably rationally better than TNF inhibitors as first-line agents for moderate to severe plaque psoriasis,” she said.

In this debate, dermatologists and rheumatologists cited studies showing the safety and efficacy of IL-17 and IL-23 inhibitors over TNF inhibitors. TNF inhibitors include etanercept (Enbrel and biosimilars), infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi). IL-12/23 inhibitors are limited to ustekinumab (Stelara). IL-17 inhibitors include secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). IL-23 inhibitors include guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi).

TNF inhibitors are recommended by the American College of Rheumatology as first-line therapy for treatment-naive patients with active PsA, and they, along with IL-12/23, IL-17, and IL-23 inhibitors are all recommended by the American Academy of Dermatology as monotherapy treatment options in adult patients with moderate to severe plaque psoriasis. However, some studies have shown that non–TNF-inhibitor biologics have a higher efficacy than TNF inhibitors in some cases for some patients, such as those with moderate to severe psoriasis alone or for musculoskeletal efficacy in patients with PsA who have peripheral arthritis, enthesitis, dactylitis, or axial manifestations.

Favorable characteristics of non–TNF-inhibitor biologics

Dr. Armstrong cited a number of head-to-head trials to support her view that IL-17 and IL-23 inhibitors are better than TNF inhibitors as first-line agents for patients with moderate to severe plaque psoriasis. In the first head-to-head study of its kind in patients with moderate to severe psoriasis, ustekinumab proved superior to etanercept. Guselkumab was shown to be superior to adalimumab for patients with moderate to severe psoriasis. Tildrakizumab also proved superior to etanercept for patients with psoriasis. Risankizumab bested adalimumab in patients with moderate to severe psoriasis. Ixekizumab proved superior to etanercept in two pivotal studies of patients with widespread moderate-to-severe psoriasis.

IL-23 and IL-17 inhibitors tend to have less frequent maintenance dosing, with IL-17 inhibitors being once every 2 or 4 weeks and IL-23 inhibitors once every 8 or 12 weeks, compared with frequencies ranging from every week to every 8 weeks with TNF inhibitors, Dr. Armstrong said.

IL-17 and IL-23 inhibitors also appear to have fewer safety concerns than TNF inhibitors, although there is less long-term data for them overall and there are some notable exceptions in certain patient populations. TNF inhibitors should be avoided in patients with a history of demyelinating disease or hepatitis B virus infection, and they are not preferred in patients who have a history of latent tuberculosis or advanced heart failure. IL-17 inhibitors should not be used in patients with a history of inflammatory bowel disease, and their use is associated with a higher rate of oral candidiasis. IL-23 inhibitors have a good safety profile overall, she said.

“The IL-17/23 axis is very important to psoriatic arthritis and should be the focus of our treatments” for PsA, said Deepak Jadon, MBBCh, MRCP, PhD, a rheumatologist and director of the rheumatology research unit at Addenbrooke’s Hospital, Cambridge (England) University Hospitals NHS Foundation Trust. In his presentation, he proposed that IL-17 inhibitors and IL-23 inhibitors be used as first-line therapies in PsA ahead of TNF inhibitors.

One reason to go with IL-17 and IL-23 inhibitors may be to ”get it right immunologically the first time,” Dr. Jadon said. He cited evidence showing substantially better response to guselkumab when given to biologic-naive patients with PsA versus those who had a inadequate response to TNF inhibitors, as well as data indicating better response with secukinumab regardless of previous TNF inhibitor use.

IL-17 inhibitors target more domains of psoriatic disease than do TNF inhibitors, he said, noting that “they have excellent musculoskeletal efficacy in patients with moderate skin psoriasis, not just those with severe psoriasis.” Ixekizumab proved superior to adalimumab in biologic-naive patients with PsA. The results of this study also indicated that IL-17 inhibitors should not be reserved only for patients with severe psoriasis since a higher percentage of patients with moderate psoriasis who were taking ixekizumab achieved very low PsA activity. Secukinumab also beat adalimumab in a head-to-head comparison and showed a greater impact on some measures of health-related quality of life.

IL-17 inhibitors also do not require concomitant methotrexate, he said, “which is a major bonus for our patients. All of my patients wish to stop methotrexate even if tolerated. Not having to cope with prescribed methotrexate improves risk of adverse events and frequency of blood test monitoring.”

IL-17 and IL-23 inhibitors appear to have good efficacy against axial disease in patients with PsA. Randomized trial results for secukinumab versus placebo show high percentages of patients improving either 20% or 40% in Assessment in Spondyloarthritis International Society response criteria and reduced inflammatory MRI lesions in the spine and sacroiliac joints. Analyses of trial results in guselkumab-treated patients with axial manifestations of PsA have shown the IL-23 inhibitor’s efficacy versus placebo across different measures of disease activity.

Dr. Jadon also cited real-world data showing that patients stay longer on IL-17 and IL-12/23 inhibitors versus TNF inhibitors. A 2016 study of patients with psoriasis in the PSOLAR registry showed that patients persisted on treatment longer with ustekinumab than with adalimumab, etanercept, or infliximab. Similarly, a 2020 study of patients with psoriasis from the British Association of Dermatologists Biologics and Immunomodulators Register found that both ustekinumab and secukinumab had better sustained drug survival than did adalimumab.


Accessibility weighs heavily in using TNF inhibitor first

Clinical trials data show that IL-17 inhibitors outperform TNF inhibitors for psoriasis, but in clinical practice, TNF inhibitors still perform very well in individual patients and are well tolerated, said Amit Garg, MD, founding chair of the department of dermatology at Hofstra University, Hempstead, N.Y.

He argued in favor of TNF inhibitors as first-line therapy over IL-17 inhibitors for psoriasis. In this case, treatment decisions often come down to accessibility, Dr. Garg said. Not all insurance companies cover the cost of the newer IL-23 inhibitors. Plus, access to TNF inhibitors is widespread and costs are generally lower.

“As a physician, I don’t have complete autonomy in prescribing what I want. The reality is whether it be because of cross indication or discount pricing, [TNF inhibitors] – in particular adalimumab – is widely available on all plans and is usually the preferred treatment plan, at least in our area,” he said. “I’m not a big fan of plans that allow drugs at low or no cost for a year or 2, and then abandon the patients at that point thereafter. I like to use something that insurance will cover sustainably, and, quite frankly, TNFs have served well in that regard.”

However, TNF inhibitors are associated with more safety signals, plus they carry a greater risk of infection, leading to tolerability and persistence issues with patients.

“Psoriasis is a lifelong disease. I wish I could tell you that every drug is going to work well forever for individual patients, but I don’t think we know that yet. From my perspective, for efficacy, general well tolerance, convenience, and access, TNFs are still an important part of our ability to treat psoriasis effectively. I have no problem starting there and transitioning as needed for individual patients.

“In my experience, I think patients on TNFs generally do well. We don’t always get the patients clear and certainly there’s drop off of efficacy over time, but I’m not sure that’s a rationale for [changing treatment],” Dr. Garg said.

Ying Ying (Katy) Leung, MD, a rheumatologist with Singapore General Hospital, and a member of the GRAPPA peripheral arthritis working group, argued against the use of IL-17 and IL-23 inhibitors as first-line treatment for PsA over TNF inhibitors. She reasoned that TNF blockers are more accessible, have more long-term safety data (including data indicating safety during pregnancy), and have better cardiovascular protection. She also noted that GRAPPA treatment recommendations strongly advise using TNF blockers (or IL-17 inhibitors) for treatment-naive patients with PsA.

“Accessibility is very important as I learned along the way of leading the peripheral arthritis [GRAPPA] working group. Accessibility [issues] can be coming from a lot of sources, but if you don’t take good care of accessibility, you might be developing a guideline that is way out of reality and nobody is going to use it,” she said.

In her native Singapore, Dr. Leung said that patients pay for biologics out of pocket, so cost is a key factor for her patients. She stated that adalimumab is available as a biosimilar at about $200 monthly for patients with PsA in Singapore, while the average monthly costs are $1,400 for originator infliximab and $1,500 for originator etanercept. By comparison, secukinumab sells for about $750 monthly, ixekizumab $540 monthly, and guselkumab $2,000 monthly.

Treatment choices should be aligned with the disease manifestations of PsA, Dr. Leung said, keeping in mind that accessibility and individual patient needs and preferences should be considered as well. She conducted an informal comparison that found TNF inhibitors are most effective for patients with uveitis or inflammatory bowel disease. Evidence from head-to-head studies indicates that TNF inhibitors and IL-17 inhibitors have similar efficacy for peripheral arthritis, enthesitis, and dactylitis. But caution is warranted, she suggested, for determining the best biologics for axial disease because no head-to-head comparison trials have been conducted for IL-17 or IL-23 inhibitors versus TNF inhibitors.

Dr. Armstrong has been a consultant to AbbVie, Bristol-Myers Squibb, Dermira, Genzyme, Incyte, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Jadon has been a consultant to, has been on speakers bureaus for, and has received grant/research support from AbbVie, Amgen, Celgene, Celltrion, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. Dr. Garg has consulted for AbbVie, Boehringer Ingelheim, Janssen, and UCB. Dr. Leung has been a consultant to AbbVie, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, and Pfizer. She has been on speakers bureaus for AbbVie, Janssen Eli Lilly, and Novartis. She has received grant/research support from Pfizer and conference support from AbbVie,

Tumor necrosis factor inhibitors have long been the go-to treatment of choice for patients with psoriasis and psoriatic arthritis (PsA). They’ve served patients well since etanercept was first approved for PsA in 2002, but today, with the availability of more attractive interleukin-17 and IL-23 inhibitors, dermatologists and rheumatologists are asking whether it’s time to reconsider the use of TNF inhibitors as first-line therapy in psoriasis and PsA.

“TNF inhibitors have served psoriasis patients well for many years. The question is, ‘Is it time to move on from them as first-line agents for psoriasis?’ ” said April W. Armstrong, MD, MPH, a dermatologist and associate dean for clinical research at the University of Southern California, Los Angeles. Dr. Armstrong participated in a point/counterpoint debate about the merits of IL-17 and IL-23 inhibitors over TNF inhibitors at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “For the majority of our patients, IL-17 and IL-23 inhibitors are probably rationally better than TNF inhibitors as first-line agents for moderate to severe plaque psoriasis,” she said.

In this debate, dermatologists and rheumatologists cited studies showing the safety and efficacy of IL-17 and IL-23 inhibitors over TNF inhibitors. TNF inhibitors include etanercept (Enbrel and biosimilars), infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi). IL-12/23 inhibitors are limited to ustekinumab (Stelara). IL-17 inhibitors include secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). IL-23 inhibitors include guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi).

TNF inhibitors are recommended by the American College of Rheumatology as first-line therapy for treatment-naive patients with active PsA, and they, along with IL-12/23, IL-17, and IL-23 inhibitors are all recommended by the American Academy of Dermatology as monotherapy treatment options in adult patients with moderate to severe plaque psoriasis. However, some studies have shown that non–TNF-inhibitor biologics have a higher efficacy than TNF inhibitors in some cases for some patients, such as those with moderate to severe psoriasis alone or for musculoskeletal efficacy in patients with PsA who have peripheral arthritis, enthesitis, dactylitis, or axial manifestations.

Favorable characteristics of non–TNF-inhibitor biologics

Dr. Armstrong cited a number of head-to-head trials to support her view that IL-17 and IL-23 inhibitors are better than TNF inhibitors as first-line agents for patients with moderate to severe plaque psoriasis. In the first head-to-head study of its kind in patients with moderate to severe psoriasis, ustekinumab proved superior to etanercept. Guselkumab was shown to be superior to adalimumab for patients with moderate to severe psoriasis. Tildrakizumab also proved superior to etanercept for patients with psoriasis. Risankizumab bested adalimumab in patients with moderate to severe psoriasis. Ixekizumab proved superior to etanercept in two pivotal studies of patients with widespread moderate-to-severe psoriasis.

IL-23 and IL-17 inhibitors tend to have less frequent maintenance dosing, with IL-17 inhibitors being once every 2 or 4 weeks and IL-23 inhibitors once every 8 or 12 weeks, compared with frequencies ranging from every week to every 8 weeks with TNF inhibitors, Dr. Armstrong said.

IL-17 and IL-23 inhibitors also appear to have fewer safety concerns than TNF inhibitors, although there is less long-term data for them overall and there are some notable exceptions in certain patient populations. TNF inhibitors should be avoided in patients with a history of demyelinating disease or hepatitis B virus infection, and they are not preferred in patients who have a history of latent tuberculosis or advanced heart failure. IL-17 inhibitors should not be used in patients with a history of inflammatory bowel disease, and their use is associated with a higher rate of oral candidiasis. IL-23 inhibitors have a good safety profile overall, she said.

“The IL-17/23 axis is very important to psoriatic arthritis and should be the focus of our treatments” for PsA, said Deepak Jadon, MBBCh, MRCP, PhD, a rheumatologist and director of the rheumatology research unit at Addenbrooke’s Hospital, Cambridge (England) University Hospitals NHS Foundation Trust. In his presentation, he proposed that IL-17 inhibitors and IL-23 inhibitors be used as first-line therapies in PsA ahead of TNF inhibitors.

One reason to go with IL-17 and IL-23 inhibitors may be to ”get it right immunologically the first time,” Dr. Jadon said. He cited evidence showing substantially better response to guselkumab when given to biologic-naive patients with PsA versus those who had a inadequate response to TNF inhibitors, as well as data indicating better response with secukinumab regardless of previous TNF inhibitor use.

IL-17 inhibitors target more domains of psoriatic disease than do TNF inhibitors, he said, noting that “they have excellent musculoskeletal efficacy in patients with moderate skin psoriasis, not just those with severe psoriasis.” Ixekizumab proved superior to adalimumab in biologic-naive patients with PsA. The results of this study also indicated that IL-17 inhibitors should not be reserved only for patients with severe psoriasis since a higher percentage of patients with moderate psoriasis who were taking ixekizumab achieved very low PsA activity. Secukinumab also beat adalimumab in a head-to-head comparison and showed a greater impact on some measures of health-related quality of life.

IL-17 inhibitors also do not require concomitant methotrexate, he said, “which is a major bonus for our patients. All of my patients wish to stop methotrexate even if tolerated. Not having to cope with prescribed methotrexate improves risk of adverse events and frequency of blood test monitoring.”

IL-17 and IL-23 inhibitors appear to have good efficacy against axial disease in patients with PsA. Randomized trial results for secukinumab versus placebo show high percentages of patients improving either 20% or 40% in Assessment in Spondyloarthritis International Society response criteria and reduced inflammatory MRI lesions in the spine and sacroiliac joints. Analyses of trial results in guselkumab-treated patients with axial manifestations of PsA have shown the IL-23 inhibitor’s efficacy versus placebo across different measures of disease activity.

Dr. Jadon also cited real-world data showing that patients stay longer on IL-17 and IL-12/23 inhibitors versus TNF inhibitors. A 2016 study of patients with psoriasis in the PSOLAR registry showed that patients persisted on treatment longer with ustekinumab than with adalimumab, etanercept, or infliximab. Similarly, a 2020 study of patients with psoriasis from the British Association of Dermatologists Biologics and Immunomodulators Register found that both ustekinumab and secukinumab had better sustained drug survival than did adalimumab.


Accessibility weighs heavily in using TNF inhibitor first

Clinical trials data show that IL-17 inhibitors outperform TNF inhibitors for psoriasis, but in clinical practice, TNF inhibitors still perform very well in individual patients and are well tolerated, said Amit Garg, MD, founding chair of the department of dermatology at Hofstra University, Hempstead, N.Y.

He argued in favor of TNF inhibitors as first-line therapy over IL-17 inhibitors for psoriasis. In this case, treatment decisions often come down to accessibility, Dr. Garg said. Not all insurance companies cover the cost of the newer IL-23 inhibitors. Plus, access to TNF inhibitors is widespread and costs are generally lower.

“As a physician, I don’t have complete autonomy in prescribing what I want. The reality is whether it be because of cross indication or discount pricing, [TNF inhibitors] – in particular adalimumab – is widely available on all plans and is usually the preferred treatment plan, at least in our area,” he said. “I’m not a big fan of plans that allow drugs at low or no cost for a year or 2, and then abandon the patients at that point thereafter. I like to use something that insurance will cover sustainably, and, quite frankly, TNFs have served well in that regard.”

However, TNF inhibitors are associated with more safety signals, plus they carry a greater risk of infection, leading to tolerability and persistence issues with patients.

“Psoriasis is a lifelong disease. I wish I could tell you that every drug is going to work well forever for individual patients, but I don’t think we know that yet. From my perspective, for efficacy, general well tolerance, convenience, and access, TNFs are still an important part of our ability to treat psoriasis effectively. I have no problem starting there and transitioning as needed for individual patients.

“In my experience, I think patients on TNFs generally do well. We don’t always get the patients clear and certainly there’s drop off of efficacy over time, but I’m not sure that’s a rationale for [changing treatment],” Dr. Garg said.

Ying Ying (Katy) Leung, MD, a rheumatologist with Singapore General Hospital, and a member of the GRAPPA peripheral arthritis working group, argued against the use of IL-17 and IL-23 inhibitors as first-line treatment for PsA over TNF inhibitors. She reasoned that TNF blockers are more accessible, have more long-term safety data (including data indicating safety during pregnancy), and have better cardiovascular protection. She also noted that GRAPPA treatment recommendations strongly advise using TNF blockers (or IL-17 inhibitors) for treatment-naive patients with PsA.

“Accessibility is very important as I learned along the way of leading the peripheral arthritis [GRAPPA] working group. Accessibility [issues] can be coming from a lot of sources, but if you don’t take good care of accessibility, you might be developing a guideline that is way out of reality and nobody is going to use it,” she said.

In her native Singapore, Dr. Leung said that patients pay for biologics out of pocket, so cost is a key factor for her patients. She stated that adalimumab is available as a biosimilar at about $200 monthly for patients with PsA in Singapore, while the average monthly costs are $1,400 for originator infliximab and $1,500 for originator etanercept. By comparison, secukinumab sells for about $750 monthly, ixekizumab $540 monthly, and guselkumab $2,000 monthly.

Treatment choices should be aligned with the disease manifestations of PsA, Dr. Leung said, keeping in mind that accessibility and individual patient needs and preferences should be considered as well. She conducted an informal comparison that found TNF inhibitors are most effective for patients with uveitis or inflammatory bowel disease. Evidence from head-to-head studies indicates that TNF inhibitors and IL-17 inhibitors have similar efficacy for peripheral arthritis, enthesitis, and dactylitis. But caution is warranted, she suggested, for determining the best biologics for axial disease because no head-to-head comparison trials have been conducted for IL-17 or IL-23 inhibitors versus TNF inhibitors.

Dr. Armstrong has been a consultant to AbbVie, Bristol-Myers Squibb, Dermira, Genzyme, Incyte, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Jadon has been a consultant to, has been on speakers bureaus for, and has received grant/research support from AbbVie, Amgen, Celgene, Celltrion, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. Dr. Garg has consulted for AbbVie, Boehringer Ingelheim, Janssen, and UCB. Dr. Leung has been a consultant to AbbVie, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, and Pfizer. She has been on speakers bureaus for AbbVie, Janssen Eli Lilly, and Novartis. She has received grant/research support from Pfizer and conference support from AbbVie,

Tumor necrosis factor inhibitors have long been the go-to treatment of choice for patients with psoriasis and psoriatic arthritis (PsA). They’ve served patients well since etanercept was first approved for PsA in 2002, but today, with the availability of more attractive interleukin-17 and IL-23 inhibitors, dermatologists and rheumatologists are asking whether it’s time to reconsider the use of TNF inhibitors as first-line therapy in psoriasis and PsA.

“TNF inhibitors have served psoriasis patients well for many years. The question is, ‘Is it time to move on from them as first-line agents for psoriasis?’ ” said April W. Armstrong, MD, MPH, a dermatologist and associate dean for clinical research at the University of Southern California, Los Angeles. Dr. Armstrong participated in a point/counterpoint debate about the merits of IL-17 and IL-23 inhibitors over TNF inhibitors at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. “For the majority of our patients, IL-17 and IL-23 inhibitors are probably rationally better than TNF inhibitors as first-line agents for moderate to severe plaque psoriasis,” she said.

In this debate, dermatologists and rheumatologists cited studies showing the safety and efficacy of IL-17 and IL-23 inhibitors over TNF inhibitors. TNF inhibitors include etanercept (Enbrel and biosimilars), infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), certolizumab pegol (Cimzia), and golimumab (Simponi). IL-12/23 inhibitors are limited to ustekinumab (Stelara). IL-17 inhibitors include secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq). IL-23 inhibitors include guselkumab (Tremfya), tildrakizumab (Ilumya), and risankizumab (Skyrizi).

TNF inhibitors are recommended by the American College of Rheumatology as first-line therapy for treatment-naive patients with active PsA, and they, along with IL-12/23, IL-17, and IL-23 inhibitors are all recommended by the American Academy of Dermatology as monotherapy treatment options in adult patients with moderate to severe plaque psoriasis. However, some studies have shown that non–TNF-inhibitor biologics have a higher efficacy than TNF inhibitors in some cases for some patients, such as those with moderate to severe psoriasis alone or for musculoskeletal efficacy in patients with PsA who have peripheral arthritis, enthesitis, dactylitis, or axial manifestations.

Favorable characteristics of non–TNF-inhibitor biologics

Dr. Armstrong cited a number of head-to-head trials to support her view that IL-17 and IL-23 inhibitors are better than TNF inhibitors as first-line agents for patients with moderate to severe plaque psoriasis. In the first head-to-head study of its kind in patients with moderate to severe psoriasis, ustekinumab proved superior to etanercept. Guselkumab was shown to be superior to adalimumab for patients with moderate to severe psoriasis. Tildrakizumab also proved superior to etanercept for patients with psoriasis. Risankizumab bested adalimumab in patients with moderate to severe psoriasis. Ixekizumab proved superior to etanercept in two pivotal studies of patients with widespread moderate-to-severe psoriasis.

IL-23 and IL-17 inhibitors tend to have less frequent maintenance dosing, with IL-17 inhibitors being once every 2 or 4 weeks and IL-23 inhibitors once every 8 or 12 weeks, compared with frequencies ranging from every week to every 8 weeks with TNF inhibitors, Dr. Armstrong said.

IL-17 and IL-23 inhibitors also appear to have fewer safety concerns than TNF inhibitors, although there is less long-term data for them overall and there are some notable exceptions in certain patient populations. TNF inhibitors should be avoided in patients with a history of demyelinating disease or hepatitis B virus infection, and they are not preferred in patients who have a history of latent tuberculosis or advanced heart failure. IL-17 inhibitors should not be used in patients with a history of inflammatory bowel disease, and their use is associated with a higher rate of oral candidiasis. IL-23 inhibitors have a good safety profile overall, she said.

“The IL-17/23 axis is very important to psoriatic arthritis and should be the focus of our treatments” for PsA, said Deepak Jadon, MBBCh, MRCP, PhD, a rheumatologist and director of the rheumatology research unit at Addenbrooke’s Hospital, Cambridge (England) University Hospitals NHS Foundation Trust. In his presentation, he proposed that IL-17 inhibitors and IL-23 inhibitors be used as first-line therapies in PsA ahead of TNF inhibitors.

One reason to go with IL-17 and IL-23 inhibitors may be to ”get it right immunologically the first time,” Dr. Jadon said. He cited evidence showing substantially better response to guselkumab when given to biologic-naive patients with PsA versus those who had a inadequate response to TNF inhibitors, as well as data indicating better response with secukinumab regardless of previous TNF inhibitor use.

IL-17 inhibitors target more domains of psoriatic disease than do TNF inhibitors, he said, noting that “they have excellent musculoskeletal efficacy in patients with moderate skin psoriasis, not just those with severe psoriasis.” Ixekizumab proved superior to adalimumab in biologic-naive patients with PsA. The results of this study also indicated that IL-17 inhibitors should not be reserved only for patients with severe psoriasis since a higher percentage of patients with moderate psoriasis who were taking ixekizumab achieved very low PsA activity. Secukinumab also beat adalimumab in a head-to-head comparison and showed a greater impact on some measures of health-related quality of life.

IL-17 inhibitors also do not require concomitant methotrexate, he said, “which is a major bonus for our patients. All of my patients wish to stop methotrexate even if tolerated. Not having to cope with prescribed methotrexate improves risk of adverse events and frequency of blood test monitoring.”

IL-17 and IL-23 inhibitors appear to have good efficacy against axial disease in patients with PsA. Randomized trial results for secukinumab versus placebo show high percentages of patients improving either 20% or 40% in Assessment in Spondyloarthritis International Society response criteria and reduced inflammatory MRI lesions in the spine and sacroiliac joints. Analyses of trial results in guselkumab-treated patients with axial manifestations of PsA have shown the IL-23 inhibitor’s efficacy versus placebo across different measures of disease activity.

Dr. Jadon also cited real-world data showing that patients stay longer on IL-17 and IL-12/23 inhibitors versus TNF inhibitors. A 2016 study of patients with psoriasis in the PSOLAR registry showed that patients persisted on treatment longer with ustekinumab than with adalimumab, etanercept, or infliximab. Similarly, a 2020 study of patients with psoriasis from the British Association of Dermatologists Biologics and Immunomodulators Register found that both ustekinumab and secukinumab had better sustained drug survival than did adalimumab.


Accessibility weighs heavily in using TNF inhibitor first

Clinical trials data show that IL-17 inhibitors outperform TNF inhibitors for psoriasis, but in clinical practice, TNF inhibitors still perform very well in individual patients and are well tolerated, said Amit Garg, MD, founding chair of the department of dermatology at Hofstra University, Hempstead, N.Y.

He argued in favor of TNF inhibitors as first-line therapy over IL-17 inhibitors for psoriasis. In this case, treatment decisions often come down to accessibility, Dr. Garg said. Not all insurance companies cover the cost of the newer IL-23 inhibitors. Plus, access to TNF inhibitors is widespread and costs are generally lower.

“As a physician, I don’t have complete autonomy in prescribing what I want. The reality is whether it be because of cross indication or discount pricing, [TNF inhibitors] – in particular adalimumab – is widely available on all plans and is usually the preferred treatment plan, at least in our area,” he said. “I’m not a big fan of plans that allow drugs at low or no cost for a year or 2, and then abandon the patients at that point thereafter. I like to use something that insurance will cover sustainably, and, quite frankly, TNFs have served well in that regard.”

However, TNF inhibitors are associated with more safety signals, plus they carry a greater risk of infection, leading to tolerability and persistence issues with patients.

“Psoriasis is a lifelong disease. I wish I could tell you that every drug is going to work well forever for individual patients, but I don’t think we know that yet. From my perspective, for efficacy, general well tolerance, convenience, and access, TNFs are still an important part of our ability to treat psoriasis effectively. I have no problem starting there and transitioning as needed for individual patients.

“In my experience, I think patients on TNFs generally do well. We don’t always get the patients clear and certainly there’s drop off of efficacy over time, but I’m not sure that’s a rationale for [changing treatment],” Dr. Garg said.

Ying Ying (Katy) Leung, MD, a rheumatologist with Singapore General Hospital, and a member of the GRAPPA peripheral arthritis working group, argued against the use of IL-17 and IL-23 inhibitors as first-line treatment for PsA over TNF inhibitors. She reasoned that TNF blockers are more accessible, have more long-term safety data (including data indicating safety during pregnancy), and have better cardiovascular protection. She also noted that GRAPPA treatment recommendations strongly advise using TNF blockers (or IL-17 inhibitors) for treatment-naive patients with PsA.

“Accessibility is very important as I learned along the way of leading the peripheral arthritis [GRAPPA] working group. Accessibility [issues] can be coming from a lot of sources, but if you don’t take good care of accessibility, you might be developing a guideline that is way out of reality and nobody is going to use it,” she said.

In her native Singapore, Dr. Leung said that patients pay for biologics out of pocket, so cost is a key factor for her patients. She stated that adalimumab is available as a biosimilar at about $200 monthly for patients with PsA in Singapore, while the average monthly costs are $1,400 for originator infliximab and $1,500 for originator etanercept. By comparison, secukinumab sells for about $750 monthly, ixekizumab $540 monthly, and guselkumab $2,000 monthly.

Treatment choices should be aligned with the disease manifestations of PsA, Dr. Leung said, keeping in mind that accessibility and individual patient needs and preferences should be considered as well. She conducted an informal comparison that found TNF inhibitors are most effective for patients with uveitis or inflammatory bowel disease. Evidence from head-to-head studies indicates that TNF inhibitors and IL-17 inhibitors have similar efficacy for peripheral arthritis, enthesitis, and dactylitis. But caution is warranted, she suggested, for determining the best biologics for axial disease because no head-to-head comparison trials have been conducted for IL-17 or IL-23 inhibitors versus TNF inhibitors.

Dr. Armstrong has been a consultant to AbbVie, Bristol-Myers Squibb, Dermira, Genzyme, Incyte, Janssen, Leo Pharma, Eli Lilly, Novartis, Pfizer, and UCB. Dr. Jadon has been a consultant to, has been on speakers bureaus for, and has received grant/research support from AbbVie, Amgen, Celgene, Celltrion, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB. Dr. Garg has consulted for AbbVie, Boehringer Ingelheim, Janssen, and UCB. Dr. Leung has been a consultant to AbbVie, Boehringer Ingelheim, Janssen, Eli Lilly, Novartis, and Pfizer. She has been on speakers bureaus for AbbVie, Janssen Eli Lilly, and Novartis. She has received grant/research support from Pfizer and conference support from AbbVie,

Identifying safe, effective, and affordable evidence-based dermatologic treatments for older adults can be challenging because of age-related changes in the skin, comorbidities, polypharmacy, mobility issues, and cognitive changes. Phototherapy has been shown to be an effective nonpharmacologic treatment option for multiple challenging dermatologic conditions^1-8; however, few studies have specifically examined its effectiveness in older adults. The challenge for older patients with psoriasis and dermatitis is that the conditions can be difficult to control and often require multiple treatment modalities.^9,10 Patients with psoriasis also have a higher risk for diabetes, dyslipidemia, and cardiovascular disease compared to other older patients,^11,12 which poses treatment challenges and makes nonpharmacologic treatments even more appealing.

Recent studies show that phototherapy can help decrease the use of dermatologic medications. Foerster and colleagues² found that adults with psoriasis who were treated with phototherapy significantly decreased their use of topical steroids (24.5% fewer patients required steroid creams and 31.1% fewer patients required psoriasis-specific topicals)(P<.01) while their use of non–psoriasis-specific medications did not change. Click and colleagues¹³ identified a decrease in medication costs, health care utilization, and risk for immunosuppression in patients treated with phototherapy when compared to those treated with biologics and apremilast. Methotrexate is a common dermatologic medication that is highly associated with increased risks in elderly patients because of impaired immune system function and the presence of comorbidities (eg, kidney disease, obesity, diabetes, fatty liver),¹⁴ which increase in prevalence with age. Combining phototherapy with methotrexate can substantially decrease the amount of methotrexate needed to achieve disease control,¹⁵ thereby decreasing the methotrexate-associated risks. Findings from these studies suggest that a safe, effective, cost-effective, and well-tolerated nonpharmacologic alternative, such as phototherapy, is highly desirable and should be optimized. Unfortunately, most studies that report the effectiveness of phototherapy are in younger populations.

This retrospective study aimed to (1) identify the most common dermatologic conditions treated with phototherapy in older adults, (2) examine the effectiveness and safety of phototherapy in older adults, and (3) compare the outcomes with 2 similar studies in the United Kingdom¹⁶ and Turkey.¹⁷

Methods

Design, Setting, Sample, and Statistical Analysis
The institutional review boards of Kaiser Permanente Washington Health Research Institute, Seattle, and the University of Washington, Seattle, approved this study. It was conducted in a large US multispecialty health care system (Group Health, Seattle, Washington [now Kaiser Permanente Washington]) serving approximately 600,000 patients, using billing records to identify all patients treated with phototherapy between January 1, 2015, and December 31, 2015, all who received narrowband UVB (NB-UVB) phototherapy. All adults 65 years and older who received phototherapy treatment during the 12-month study period were included. Patients were included regardless of comorbidities and other dermatologic treatments to maintain as much uniformity as possible between the present study and 2 prior studies examining phototherapy in older adult populations in the United Kingdom¹⁶ and Turkey.¹⁷ Demographic and clinical factors were presented using frequencies (percentages) or means and medians as appropriate. Comparisons of dermatologic conditions and clearance levels used a Fisher exact test. The number of phototherapy treatments to clearance and total number of treatments were compared between groups of patients using independent sample t tests.

Phototherapy Protocol
All patients received treatments administered by specially trained phototherapy nurses using a Daavlin UV Series (The Daavlin Company) or an Ultralite unit (Ultralite Enterprises, Inc), both with 48 lamps. All phototherapy nurses had been previously trained to provide treatments based on standardized protocols (Table 1) and to determine the patient’s level of disease clearance using a high to low clearance scale (Table 2). Daavlin’s treatment protocols were built into the software that accompanied the units and were developed based on the American Academy of Dermatology guidelines. The starting dose for an individual patient was determined based on the estimated minimal erythema dose for each phototype. If the patient was using photosensitizing medications, then the protocol guided the nurse to start the patient at a lower dose appropriate for their phototype. Patients with vitiligo were treated with the same starting and escalation doses as patients with Fitzpatrick phototype I because of the assumption that their vitiliginous skin had an increased risk for photosensitivity. A more recent review of the evidence has indicated that this assumption was overly conservative,¹⁸ and Kaiser Permanente Washington’s vitiligo protocol has been adjusted.

Results

Patients
Billing records identified 229 total patients who received phototherapy in 2015, of whom 52 (22.7%) were at least 65 years old. The median age was 70 years (range, 65–91 years). Twenty-nine (56%) were men and 35 (67%) had previously received phototherapy treatments.

Dermatologic Conditions Treated With Phototherapy
Our primary aim was to identify the most common dermatologic conditions treated with phototherapy in older adults. Psoriasis and dermatitis were the most common conditions treated in the sample (50% [26/52] and 21% [11/52], respectively), with mycosis fungoides being the third most common (10% [5/52]) and vitiligo tied with prurigo nodularis as fourth most common (6% [3/52])(Figure 1).

Effectiveness and Safety of Phototherapy
Our secondary aim was to examine the effectiveness and safety of phototherapy in older adults. Phototherapy was effective in this population, with 50 of 52 patients (96%) achieving a high or medium level of clearance. The degree of clearance for each of the dermatologic conditions is shown in Figure 2. Psoriasis and dermatitis achieved high clearance rates in 81% (21/26) and 82% (9/11) of patients, respectively. Overall, conditions did not have significant differences in clearances rates (Fisher exact test, P=.10). On average, it took patients 33 treatments to achieve medium or high rates of clearance. Psoriasis cleared more quickly, with an average of 30.4 treatments vs 36.1 treatments for other conditions, but the difference was not significant (t test, P=.26). Patients received an average of 98 total phototherapy treatments; the median number of treatments was 81 due to many being on maintenance therapy over several months. There was no relationship between a history of treatment with phototherapy and the total number of treatments needed to achieve clearance (t test, P=.40), but interestingly, those who had a history of phototherapy took approximately 5 more treatments to achieve clearance. The present study found that a slightly larger number of men were being treated for psoriasis (15 men vs 11 women), but there was no significant difference in response rate based on gender.

Comment

Our study found that 94% of patients with psoriasis achieved clearance with an average of 30.4 treatments, which is comparable to the reported 91% response rate with an average of 30 treatments in the United Kingdom.¹⁶ The other similar study in Turkey¹⁷ reported 73.7% of psoriasis patients achieved a 75% or more improvement from baseline with an average of 42 treatments, which may reflect underlying differences in regional skin type. Of note, the scatter chart (Figure 3) shows that several patients in the present study’s analysis are listed as not clear, but many of those patients had low treatment numbers below the mean time to clearance. Thus, the present study’s response rate may have been underestimated.

In the general population, studies show that psoriasis treated with standardized phototherapy protocols typically clears with an average of 20.6 treatments.²¹ The levels of clearance were similar in our study’s older population, but more treatments were required to achieve those results, with an average of 10 more treatments needed (an additional 3.3 weeks). Similar results were found in this sample for dermatitis and mycosis fungoides, indicating comparable clearance rates and levels but a need for more treatments to achieve similar results compared to the general population.

Additionally, in the current study more patients experienced grade 1 (mild) erythema (46%) and grade 2 erythema (25%) at some point in their treatment compared with the United Kingdom¹⁶ (1.89%) and Turkey¹⁷ (35%) studies, though these side effects did not impact the clearance rate. Interestingly, the current study’s scatter chart (Figure 3) illustrates that this side effect did not seem to increase with aging in this population. If anything, the erythema response was more prevalent in the median or younger patients in the sample. Erythema may have been due to the frequent use of photosensitizing medications in older adults in the United States, some of which typically get discontinued in patients 75 years and older (eg, statins). Other potential causes might include the use of phototype vs minimal erythema dose–driven protocols, the standard utilization of protocols originally designed for psoriasis vs other condition-specific protocols, missed treatments leading to increased sensitivity, or possibly shielding mishaps (eg, not wearing a prescribed face shield). Given the number of potential causes and the possibility of overlapping factors, careful analysis is important. With NB-UVB phototherapy, near-erythemogenic doses are optimal to achieve effective treatments, but this delicate balance may be more problematic for older adults. Future studies are needed to fully determine the factors at play for this population. In the interim, it is important for phototherapy-trained nurses to consider this risk carefully in the older population. They must follow the prescribed protocols that guide them to query patients about their responses to the prior treatment (eg, erythema, tenderness, itching), photosensitizing medications, missed treatments, and placement of shielding, and then adjust the treatment dosing accordingly.

Limitations
This study had several limitations. Although clinical outcomes were recorded prospectively, the analysis was retrospective, unblinded, and not placebo controlled. It was conducted in a single organization (Group Health [now Kaiser Permanente Washington]) but did analyze data from 4 medical centers in different cities with diverse demographics and a variety of nursing staff providing the treatments. Although the vitiligo treatment protocol likely slowed the response rate for those patients with vitiligo, the numbers were small (ie, only 3 of 52 patients), so the researchers chose to include them in the current study. The sample population was relatively small, but when these data are evaluated alongside the studies in the United Kingdom¹⁶ and Turkey,¹⁷ they show a consistent picture illustrating the effectiveness and safety of phototherapy in the older population. Further epidemiologic studies could be helpful to further describe the usefulness of this modality compared with other treatments for a variety of dermatoses in this age group. Supplementary analysis specifically examining the relationship between the number and type of photosensitizing medications, frequency of erythema, and time to clearance also could be useful.

Conclusion

Older adults with a variety of dermatoses respond well to phototherapy and should have the opportunity to use it, particularly considering the potential for increased complications and costs from other treatment modalities, such as commonly used immunosuppressive pharmaceuticals. However, the current study and the comparison studies indicate that it is important to carefully consider the slower clearance rates and the potential risk for increased erythema in this population and adjust patient education and treatment dosing accordingly.

Unfortunately, many dermatology centers do not offer phototherapy because of infrastructure limitations such as space and specially trained nursing staff. Increasing accessibility of phototherapy for older adults through home treatments may be an alternative, given its effectiveness in the general population.^22,23 In addition, home phototherapy may be worth pursuing for the older population considering the challenges they may face with transportation to the clinic setting and their increased risk for serious illness if exposed to infections such as COVID-19. The COVID-19 pandemic has brought to light the need for reliable, safe, and effective treatments that can be utilized in the safety of patients’ homes and should therefore be considered as an option for older adults. Issues such as mobility and cognitive decline could pose some complicating factors, but with the help of a well-trained family member or caregiver, home phototherapy could be a viable option that improves accessibility for older patients. Future research opportunities include further examination of the slower but ultimately equivalent response to phototherapy in the older population, the influence of photosensitizing medications on phototherapy effects, and the impact of phototherapy on utilization of immunosuppressive pharmaceuticals in older adults.

Identifying safe, effective, and affordable evidence-based dermatologic treatments for older adults can be challenging because of age-related changes in the skin, comorbidities, polypharmacy, mobility issues, and cognitive changes. Phototherapy has been shown to be an effective nonpharmacologic treatment option for multiple challenging dermatologic conditions^1-8; however, few studies have specifically examined its effectiveness in older adults. The challenge for older patients with psoriasis and dermatitis is that the conditions can be difficult to control and often require multiple treatment modalities.^9,10 Patients with psoriasis also have a higher risk for diabetes, dyslipidemia, and cardiovascular disease compared to other older patients,^11,12 which poses treatment challenges and makes nonpharmacologic treatments even more appealing.

Recent studies show that phototherapy can help decrease the use of dermatologic medications. Foerster and colleagues² found that adults with psoriasis who were treated with phototherapy significantly decreased their use of topical steroids (24.5% fewer patients required steroid creams and 31.1% fewer patients required psoriasis-specific topicals)(P<.01) while their use of non–psoriasis-specific medications did not change. Click and colleagues¹³ identified a decrease in medication costs, health care utilization, and risk for immunosuppression in patients treated with phototherapy when compared to those treated with biologics and apremilast. Methotrexate is a common dermatologic medication that is highly associated with increased risks in elderly patients because of impaired immune system function and the presence of comorbidities (eg, kidney disease, obesity, diabetes, fatty liver),¹⁴ which increase in prevalence with age. Combining phototherapy with methotrexate can substantially decrease the amount of methotrexate needed to achieve disease control,¹⁵ thereby decreasing the methotrexate-associated risks. Findings from these studies suggest that a safe, effective, cost-effective, and well-tolerated nonpharmacologic alternative, such as phototherapy, is highly desirable and should be optimized. Unfortunately, most studies that report the effectiveness of phototherapy are in younger populations.

This retrospective study aimed to (1) identify the most common dermatologic conditions treated with phototherapy in older adults, (2) examine the effectiveness and safety of phototherapy in older adults, and (3) compare the outcomes with 2 similar studies in the United Kingdom¹⁶ and Turkey.¹⁷

Methods

Design, Setting, Sample, and Statistical Analysis
The institutional review boards of Kaiser Permanente Washington Health Research Institute, Seattle, and the University of Washington, Seattle, approved this study. It was conducted in a large US multispecialty health care system (Group Health, Seattle, Washington [now Kaiser Permanente Washington]) serving approximately 600,000 patients, using billing records to identify all patients treated with phototherapy between January 1, 2015, and December 31, 2015, all who received narrowband UVB (NB-UVB) phototherapy. All adults 65 years and older who received phototherapy treatment during the 12-month study period were included. Patients were included regardless of comorbidities and other dermatologic treatments to maintain as much uniformity as possible between the present study and 2 prior studies examining phototherapy in older adult populations in the United Kingdom¹⁶ and Turkey.¹⁷ Demographic and clinical factors were presented using frequencies (percentages) or means and medians as appropriate. Comparisons of dermatologic conditions and clearance levels used a Fisher exact test. The number of phototherapy treatments to clearance and total number of treatments were compared between groups of patients using independent sample t tests.

Phototherapy Protocol
All patients received treatments administered by specially trained phototherapy nurses using a Daavlin UV Series (The Daavlin Company) or an Ultralite unit (Ultralite Enterprises, Inc), both with 48 lamps. All phototherapy nurses had been previously trained to provide treatments based on standardized protocols (Table 1) and to determine the patient’s level of disease clearance using a high to low clearance scale (Table 2). Daavlin’s treatment protocols were built into the software that accompanied the units and were developed based on the American Academy of Dermatology guidelines. The starting dose for an individual patient was determined based on the estimated minimal erythema dose for each phototype. If the patient was using photosensitizing medications, then the protocol guided the nurse to start the patient at a lower dose appropriate for their phototype. Patients with vitiligo were treated with the same starting and escalation doses as patients with Fitzpatrick phototype I because of the assumption that their vitiliginous skin had an increased risk for photosensitivity. A more recent review of the evidence has indicated that this assumption was overly conservative,¹⁸ and Kaiser Permanente Washington’s vitiligo protocol has been adjusted.

Results

Patients
Billing records identified 229 total patients who received phototherapy in 2015, of whom 52 (22.7%) were at least 65 years old. The median age was 70 years (range, 65–91 years). Twenty-nine (56%) were men and 35 (67%) had previously received phototherapy treatments.

Dermatologic Conditions Treated With Phototherapy
Our primary aim was to identify the most common dermatologic conditions treated with phototherapy in older adults. Psoriasis and dermatitis were the most common conditions treated in the sample (50% [26/52] and 21% [11/52], respectively), with mycosis fungoides being the third most common (10% [5/52]) and vitiligo tied with prurigo nodularis as fourth most common (6% [3/52])(Figure 1).

Effectiveness and Safety of Phototherapy
Our secondary aim was to examine the effectiveness and safety of phototherapy in older adults. Phototherapy was effective in this population, with 50 of 52 patients (96%) achieving a high or medium level of clearance. The degree of clearance for each of the dermatologic conditions is shown in Figure 2. Psoriasis and dermatitis achieved high clearance rates in 81% (21/26) and 82% (9/11) of patients, respectively. Overall, conditions did not have significant differences in clearances rates (Fisher exact test, P=.10). On average, it took patients 33 treatments to achieve medium or high rates of clearance. Psoriasis cleared more quickly, with an average of 30.4 treatments vs 36.1 treatments for other conditions, but the difference was not significant (t test, P=.26). Patients received an average of 98 total phototherapy treatments; the median number of treatments was 81 due to many being on maintenance therapy over several months. There was no relationship between a history of treatment with phototherapy and the total number of treatments needed to achieve clearance (t test, P=.40), but interestingly, those who had a history of phototherapy took approximately 5 more treatments to achieve clearance. The present study found that a slightly larger number of men were being treated for psoriasis (15 men vs 11 women), but there was no significant difference in response rate based on gender.

Comment

Our study found that 94% of patients with psoriasis achieved clearance with an average of 30.4 treatments, which is comparable to the reported 91% response rate with an average of 30 treatments in the United Kingdom.¹⁶ The other similar study in Turkey¹⁷ reported 73.7% of psoriasis patients achieved a 75% or more improvement from baseline with an average of 42 treatments, which may reflect underlying differences in regional skin type. Of note, the scatter chart (Figure 3) shows that several patients in the present study’s analysis are listed as not clear, but many of those patients had low treatment numbers below the mean time to clearance. Thus, the present study’s response rate may have been underestimated.

In the general population, studies show that psoriasis treated with standardized phototherapy protocols typically clears with an average of 20.6 treatments.²¹ The levels of clearance were similar in our study’s older population, but more treatments were required to achieve those results, with an average of 10 more treatments needed (an additional 3.3 weeks). Similar results were found in this sample for dermatitis and mycosis fungoides, indicating comparable clearance rates and levels but a need for more treatments to achieve similar results compared to the general population.

Additionally, in the current study more patients experienced grade 1 (mild) erythema (46%) and grade 2 erythema (25%) at some point in their treatment compared with the United Kingdom¹⁶ (1.89%) and Turkey¹⁷ (35%) studies, though these side effects did not impact the clearance rate. Interestingly, the current study’s scatter chart (Figure 3) illustrates that this side effect did not seem to increase with aging in this population. If anything, the erythema response was more prevalent in the median or younger patients in the sample. Erythema may have been due to the frequent use of photosensitizing medications in older adults in the United States, some of which typically get discontinued in patients 75 years and older (eg, statins). Other potential causes might include the use of phototype vs minimal erythema dose–driven protocols, the standard utilization of protocols originally designed for psoriasis vs other condition-specific protocols, missed treatments leading to increased sensitivity, or possibly shielding mishaps (eg, not wearing a prescribed face shield). Given the number of potential causes and the possibility of overlapping factors, careful analysis is important. With NB-UVB phototherapy, near-erythemogenic doses are optimal to achieve effective treatments, but this delicate balance may be more problematic for older adults. Future studies are needed to fully determine the factors at play for this population. In the interim, it is important for phototherapy-trained nurses to consider this risk carefully in the older population. They must follow the prescribed protocols that guide them to query patients about their responses to the prior treatment (eg, erythema, tenderness, itching), photosensitizing medications, missed treatments, and placement of shielding, and then adjust the treatment dosing accordingly.

Limitations
This study had several limitations. Although clinical outcomes were recorded prospectively, the analysis was retrospective, unblinded, and not placebo controlled. It was conducted in a single organization (Group Health [now Kaiser Permanente Washington]) but did analyze data from 4 medical centers in different cities with diverse demographics and a variety of nursing staff providing the treatments. Although the vitiligo treatment protocol likely slowed the response rate for those patients with vitiligo, the numbers were small (ie, only 3 of 52 patients), so the researchers chose to include them in the current study. The sample population was relatively small, but when these data are evaluated alongside the studies in the United Kingdom¹⁶ and Turkey,¹⁷ they show a consistent picture illustrating the effectiveness and safety of phototherapy in the older population. Further epidemiologic studies could be helpful to further describe the usefulness of this modality compared with other treatments for a variety of dermatoses in this age group. Supplementary analysis specifically examining the relationship between the number and type of photosensitizing medications, frequency of erythema, and time to clearance also could be useful.

Conclusion

Older adults with a variety of dermatoses respond well to phototherapy and should have the opportunity to use it, particularly considering the potential for increased complications and costs from other treatment modalities, such as commonly used immunosuppressive pharmaceuticals. However, the current study and the comparison studies indicate that it is important to carefully consider the slower clearance rates and the potential risk for increased erythema in this population and adjust patient education and treatment dosing accordingly.

Unfortunately, many dermatology centers do not offer phototherapy because of infrastructure limitations such as space and specially trained nursing staff. Increasing accessibility of phototherapy for older adults through home treatments may be an alternative, given its effectiveness in the general population.^22,23 In addition, home phototherapy may be worth pursuing for the older population considering the challenges they may face with transportation to the clinic setting and their increased risk for serious illness if exposed to infections such as COVID-19. The COVID-19 pandemic has brought to light the need for reliable, safe, and effective treatments that can be utilized in the safety of patients’ homes and should therefore be considered as an option for older adults. Issues such as mobility and cognitive decline could pose some complicating factors, but with the help of a well-trained family member or caregiver, home phototherapy could be a viable option that improves accessibility for older patients. Future research opportunities include further examination of the slower but ultimately equivalent response to phototherapy in the older population, the influence of photosensitizing medications on phototherapy effects, and the impact of phototherapy on utilization of immunosuppressive pharmaceuticals in older adults.

Identifying safe, effective, and affordable evidence-based dermatologic treatments for older adults can be challenging because of age-related changes in the skin, comorbidities, polypharmacy, mobility issues, and cognitive changes. Phototherapy has been shown to be an effective nonpharmacologic treatment option for multiple challenging dermatologic conditions^1-8; however, few studies have specifically examined its effectiveness in older adults. The challenge for older patients with psoriasis and dermatitis is that the conditions can be difficult to control and often require multiple treatment modalities.^9,10 Patients with psoriasis also have a higher risk for diabetes, dyslipidemia, and cardiovascular disease compared to other older patients,^11,12 which poses treatment challenges and makes nonpharmacologic treatments even more appealing.

Recent studies show that phototherapy can help decrease the use of dermatologic medications. Foerster and colleagues² found that adults with psoriasis who were treated with phototherapy significantly decreased their use of topical steroids (24.5% fewer patients required steroid creams and 31.1% fewer patients required psoriasis-specific topicals)(P<.01) while their use of non–psoriasis-specific medications did not change. Click and colleagues¹³ identified a decrease in medication costs, health care utilization, and risk for immunosuppression in patients treated with phototherapy when compared to those treated with biologics and apremilast. Methotrexate is a common dermatologic medication that is highly associated with increased risks in elderly patients because of impaired immune system function and the presence of comorbidities (eg, kidney disease, obesity, diabetes, fatty liver),¹⁴ which increase in prevalence with age. Combining phototherapy with methotrexate can substantially decrease the amount of methotrexate needed to achieve disease control,¹⁵ thereby decreasing the methotrexate-associated risks. Findings from these studies suggest that a safe, effective, cost-effective, and well-tolerated nonpharmacologic alternative, such as phototherapy, is highly desirable and should be optimized. Unfortunately, most studies that report the effectiveness of phototherapy are in younger populations.

This retrospective study aimed to (1) identify the most common dermatologic conditions treated with phototherapy in older adults, (2) examine the effectiveness and safety of phototherapy in older adults, and (3) compare the outcomes with 2 similar studies in the United Kingdom¹⁶ and Turkey.¹⁷

Methods

Design, Setting, Sample, and Statistical Analysis
The institutional review boards of Kaiser Permanente Washington Health Research Institute, Seattle, and the University of Washington, Seattle, approved this study. It was conducted in a large US multispecialty health care system (Group Health, Seattle, Washington [now Kaiser Permanente Washington]) serving approximately 600,000 patients, using billing records to identify all patients treated with phototherapy between January 1, 2015, and December 31, 2015, all who received narrowband UVB (NB-UVB) phototherapy. All adults 65 years and older who received phototherapy treatment during the 12-month study period were included. Patients were included regardless of comorbidities and other dermatologic treatments to maintain as much uniformity as possible between the present study and 2 prior studies examining phototherapy in older adult populations in the United Kingdom¹⁶ and Turkey.¹⁷ Demographic and clinical factors were presented using frequencies (percentages) or means and medians as appropriate. Comparisons of dermatologic conditions and clearance levels used a Fisher exact test. The number of phototherapy treatments to clearance and total number of treatments were compared between groups of patients using independent sample t tests.

Phototherapy Protocol
All patients received treatments administered by specially trained phototherapy nurses using a Daavlin UV Series (The Daavlin Company) or an Ultralite unit (Ultralite Enterprises, Inc), both with 48 lamps. All phototherapy nurses had been previously trained to provide treatments based on standardized protocols (Table 1) and to determine the patient’s level of disease clearance using a high to low clearance scale (Table 2). Daavlin’s treatment protocols were built into the software that accompanied the units and were developed based on the American Academy of Dermatology guidelines. The starting dose for an individual patient was determined based on the estimated minimal erythema dose for each phototype. If the patient was using photosensitizing medications, then the protocol guided the nurse to start the patient at a lower dose appropriate for their phototype. Patients with vitiligo were treated with the same starting and escalation doses as patients with Fitzpatrick phototype I because of the assumption that their vitiliginous skin had an increased risk for photosensitivity. A more recent review of the evidence has indicated that this assumption was overly conservative,¹⁸ and Kaiser Permanente Washington’s vitiligo protocol has been adjusted.

Results

Patients
Billing records identified 229 total patients who received phototherapy in 2015, of whom 52 (22.7%) were at least 65 years old. The median age was 70 years (range, 65–91 years). Twenty-nine (56%) were men and 35 (67%) had previously received phototherapy treatments.

Dermatologic Conditions Treated With Phototherapy
Our primary aim was to identify the most common dermatologic conditions treated with phototherapy in older adults. Psoriasis and dermatitis were the most common conditions treated in the sample (50% [26/52] and 21% [11/52], respectively), with mycosis fungoides being the third most common (10% [5/52]) and vitiligo tied with prurigo nodularis as fourth most common (6% [3/52])(Figure 1).

Effectiveness and Safety of Phototherapy
Our secondary aim was to examine the effectiveness and safety of phototherapy in older adults. Phototherapy was effective in this population, with 50 of 52 patients (96%) achieving a high or medium level of clearance. The degree of clearance for each of the dermatologic conditions is shown in Figure 2. Psoriasis and dermatitis achieved high clearance rates in 81% (21/26) and 82% (9/11) of patients, respectively. Overall, conditions did not have significant differences in clearances rates (Fisher exact test, P=.10). On average, it took patients 33 treatments to achieve medium or high rates of clearance. Psoriasis cleared more quickly, with an average of 30.4 treatments vs 36.1 treatments for other conditions, but the difference was not significant (t test, P=.26). Patients received an average of 98 total phototherapy treatments; the median number of treatments was 81 due to many being on maintenance therapy over several months. There was no relationship between a history of treatment with phototherapy and the total number of treatments needed to achieve clearance (t test, P=.40), but interestingly, those who had a history of phototherapy took approximately 5 more treatments to achieve clearance. The present study found that a slightly larger number of men were being treated for psoriasis (15 men vs 11 women), but there was no significant difference in response rate based on gender.

Comment

Our study found that 94% of patients with psoriasis achieved clearance with an average of 30.4 treatments, which is comparable to the reported 91% response rate with an average of 30 treatments in the United Kingdom.¹⁶ The other similar study in Turkey¹⁷ reported 73.7% of psoriasis patients achieved a 75% or more improvement from baseline with an average of 42 treatments, which may reflect underlying differences in regional skin type. Of note, the scatter chart (Figure 3) shows that several patients in the present study’s analysis are listed as not clear, but many of those patients had low treatment numbers below the mean time to clearance. Thus, the present study’s response rate may have been underestimated.

In the general population, studies show that psoriasis treated with standardized phototherapy protocols typically clears with an average of 20.6 treatments.²¹ The levels of clearance were similar in our study’s older population, but more treatments were required to achieve those results, with an average of 10 more treatments needed (an additional 3.3 weeks). Similar results were found in this sample for dermatitis and mycosis fungoides, indicating comparable clearance rates and levels but a need for more treatments to achieve similar results compared to the general population.

Additionally, in the current study more patients experienced grade 1 (mild) erythema (46%) and grade 2 erythema (25%) at some point in their treatment compared with the United Kingdom¹⁶ (1.89%) and Turkey¹⁷ (35%) studies, though these side effects did not impact the clearance rate. Interestingly, the current study’s scatter chart (Figure 3) illustrates that this side effect did not seem to increase with aging in this population. If anything, the erythema response was more prevalent in the median or younger patients in the sample. Erythema may have been due to the frequent use of photosensitizing medications in older adults in the United States, some of which typically get discontinued in patients 75 years and older (eg, statins). Other potential causes might include the use of phototype vs minimal erythema dose–driven protocols, the standard utilization of protocols originally designed for psoriasis vs other condition-specific protocols, missed treatments leading to increased sensitivity, or possibly shielding mishaps (eg, not wearing a prescribed face shield). Given the number of potential causes and the possibility of overlapping factors, careful analysis is important. With NB-UVB phototherapy, near-erythemogenic doses are optimal to achieve effective treatments, but this delicate balance may be more problematic for older adults. Future studies are needed to fully determine the factors at play for this population. In the interim, it is important for phototherapy-trained nurses to consider this risk carefully in the older population. They must follow the prescribed protocols that guide them to query patients about their responses to the prior treatment (eg, erythema, tenderness, itching), photosensitizing medications, missed treatments, and placement of shielding, and then adjust the treatment dosing accordingly.

Limitations
This study had several limitations. Although clinical outcomes were recorded prospectively, the analysis was retrospective, unblinded, and not placebo controlled. It was conducted in a single organization (Group Health [now Kaiser Permanente Washington]) but did analyze data from 4 medical centers in different cities with diverse demographics and a variety of nursing staff providing the treatments. Although the vitiligo treatment protocol likely slowed the response rate for those patients with vitiligo, the numbers were small (ie, only 3 of 52 patients), so the researchers chose to include them in the current study. The sample population was relatively small, but when these data are evaluated alongside the studies in the United Kingdom¹⁶ and Turkey,¹⁷ they show a consistent picture illustrating the effectiveness and safety of phototherapy in the older population. Further epidemiologic studies could be helpful to further describe the usefulness of this modality compared with other treatments for a variety of dermatoses in this age group. Supplementary analysis specifically examining the relationship between the number and type of photosensitizing medications, frequency of erythema, and time to clearance also could be useful.

Conclusion

Older adults with a variety of dermatoses respond well to phototherapy and should have the opportunity to use it, particularly considering the potential for increased complications and costs from other treatment modalities, such as commonly used immunosuppressive pharmaceuticals. However, the current study and the comparison studies indicate that it is important to carefully consider the slower clearance rates and the potential risk for increased erythema in this population and adjust patient education and treatment dosing accordingly.

Unfortunately, many dermatology centers do not offer phototherapy because of infrastructure limitations such as space and specially trained nursing staff. Increasing accessibility of phototherapy for older adults through home treatments may be an alternative, given its effectiveness in the general population.^22,23 In addition, home phototherapy may be worth pursuing for the older population considering the challenges they may face with transportation to the clinic setting and their increased risk for serious illness if exposed to infections such as COVID-19. The COVID-19 pandemic has brought to light the need for reliable, safe, and effective treatments that can be utilized in the safety of patients’ homes and should therefore be considered as an option for older adults. Issues such as mobility and cognitive decline could pose some complicating factors, but with the help of a well-trained family member or caregiver, home phototherapy could be a viable option that improves accessibility for older patients. Future research opportunities include further examination of the slower but ultimately equivalent response to phototherapy in the older population, the influence of photosensitizing medications on phototherapy effects, and the impact of phototherapy on utilization of immunosuppressive pharmaceuticals in older adults.

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association (TMA) calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

Eighty-seven percent of Texas physicians reported a “drastic increase over the past five years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association (AMA), said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient, said Dr. Patt.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says, ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to re-engage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said, “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are an “an important way” to deliver “safe, high-quality care” to patients, she added.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA supports the Improving Seniors’ Timely Access to Care Act (HR 3173). The act includes a provision related to “gold-carding,” said Robert Mills, an AMA spokesperson.

The bill establishes requirements and standards for prior authorization processes related to Medicare Advantage (MA) plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

The act was introduced to the U.S. House of Representatives in May, after which it was referred to two committees for consideration.

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

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association (TMA) calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

Eighty-seven percent of Texas physicians reported a “drastic increase over the past five years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association (AMA), said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient, said Dr. Patt.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says, ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to re-engage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said, “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are an “an important way” to deliver “safe, high-quality care” to patients, she added.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA supports the Improving Seniors’ Timely Access to Care Act (HR 3173). The act includes a provision related to “gold-carding,” said Robert Mills, an AMA spokesperson.

The bill establishes requirements and standards for prior authorization processes related to Medicare Advantage (MA) plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

The act was introduced to the U.S. House of Representatives in May, after which it was referred to two committees for consideration.

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

In what could be a model for other states, Texas has become the first state to exempt physicians from prior authorizations for meeting insurer benchmarks.

The law was passed in June and will take effect in September. It excuses physicians from having to obtain prior authorization if, during the previous 6 months, 90% of their treatments met medical necessity criteria by the health insurer. Through this law, doctors in the state will spend less time getting approvals for treatments for their patients.

Automatic approval of authorizations for treatments – or what the Texas Medical Association (TMA) calls a “gold card” – “allows patients to get the care they need in a more timely fashion,” says Debra Patt, MD, an Austin, Tex.–based oncologist and former chair of the council on legislation for the TMA.

Eighty-seven percent of Texas physicians reported a “drastic increase over the past five years in the burden of prior authorization on their patients and their practices,” per a 2020 survey by the TMA. Nearly half (48%) of Texas physicians have hired staff whose work focuses on processing requests for prior authorization, according to the survey.

Jack Resneck Jr., MD, a San Francisco–based dermatologist and president-elect of the American Medical Association (AMA), said other states have investigated ways to ease the impact of prior authorizations on physicians, but no other state has passed such a law.

Administrative burdens plague physicians around the country. The Medscape Physician Compensation Report 2021 found that physicians spend on average 15.6 hours per week on paperwork and administrative duties.
 

Better outcomes, less anxiety for patients

Dr. Patt, who testified in support of the law’s passage in the Texas legislature, says automatic approval of authorizations “is better for patients because it reduces their anxiety about whether they’re able to get the treatments they need now, and they will have better outcomes if they’re able to receive more timely care.”

Recently, a chemotherapy treatment Dr. Patt prescribed for one of her patients was not authorized by an insurer. The result is “a lot of anxiety and potentially health problems” for the patient, said Dr. Patt.

She expects that automatic approval for treatments will be based on prescribing patterns during the preceding 6 months. “It means that when I order a test today, the [health insurer] looks back at my record 6 months previously,” she said. Still, Dr. Patt awaits guidance from the Texas Department of Insurance, which regulates health insurers in the state, regarding the law.

Dr. Resneck said the pharmacy counter is where most patients encounter prior authorization delays. “That’s when the pharmacist looks at them and says, ‘Actually, this isn’t covered by your health insurer’s formulary,’ or it isn’t covered fully on their formulary.”

One of Dr. Resneck’s patients had a life-altering case of eczema that lasted many years. Because of the condition, the patient couldn’t work or maintain meaningful bonds with family members. A biologic treatment transformed his patient’s life. The patient was able to return to work and to re-engage with family, said Dr. Resneck. But a year after his patient started the treatment, the health insurer wouldn’t authorize the treatment because the patient wasn’t experiencing the same symptoms.

The patient didn’t have the same symptoms because the biologic treatment worked, said Dr. Resneck.

Kristine Grow, a spokesperson for America’s Health Insurance Plans, a national association for health insurers, said, “The use of prior authorization is relatively small – typically, less than 15% – and can help ensure safer opioid prescribing, help prevent dangerous drug interactions, and help protect patients from unnecessary exposure to potentially harmful radiation for inappropriate diagnostic imaging. Numerous studies show that Americans frequently receive inappropriate care, and 25% of unnecessary treatments are associated with complications or adverse events.”

Medical management tools, such as prior authorization, are an “an important way” to deliver “safe, high-quality care” to patients, she added.
 

State and federal efforts to curb prior authorization

In addition to efforts to curb prior authorization in other states, the AMA supports the Improving Seniors’ Timely Access to Care Act (HR 3173). The act includes a provision related to “gold-carding,” said Robert Mills, an AMA spokesperson.

The bill establishes requirements and standards for prior authorization processes related to Medicare Advantage (MA) plans. The requirements and standards for MA plans include the following:

• Establishing an electronic prior authorization program that meets specific standards, such as the ability to provide real-time decisions in response to requests for items and services that are routinely approved.
• Publishing on an annual basis specific prior authorization information, including the percentage of requests approved and the average response time.
• Meeting standards set by the Centers for Medicare & Medicaid Services related to the quality and timeliness of prior authorization determinations.

The act was introduced to the U.S. House of Representatives in May, after which it was referred to two committees for consideration.

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

The Comparison

A Elbow and forearm with erythematous, well-demarcated, pink plaques with mild micaceous scale in a 42-year-old White woman.

B Elbow and forearm with violaceous, well-demarcated plaques with micaceous scale and hyperpigmented patches around the active plaques in a 58-year-old Black man.

Epidemiology
Psoriasis prevalence in the United States has been estimated at 3.7%.^1-3 If broken down by race or ethnicity, the prevalence of psoriasis varies: 2.5% to 3.7% in White adults^1-4; 1.3% to 2% in Black adults^1-4; 1.6% in Hispanics/ other adults^1-3; 1% in children overall; 0.29% in White children_^1,5; and 0.06% in Black children.^1,5

Key clinical features in people with darker skin tones include:

• plaques that may appear more violaceous in color instead of pink or erythematous
• higher body surface area of involvement4 and thicker, more scaly plaques⁶
• increased likelihood of postinflammatory hyperpigmentation (PIH).

Worth noting
Although individuals of all skin tones may experience the psychosocial impact of psoriasis, quality-of-life measures have been found to be worse in those with skin of color (SOC) compared to White patients.^1,4 This may be due to the lingering PIH and hypopigmentation that occurs even after inflammatory plaques are treated. Of course, lack of access to care contributes to greater disease burden and more devastating psychological impact.

Health disparity highlight
Psoriasis may be underreported and underdiagnosed in individuals with SOC, as factors contributing to health care disparities may play a role, such as access to health care in general,^1,7 and access to clinicians proficient in diagnosing cutaneous diseases in SOC may be delayed.⁸

Biologic medications are used less often in Black patients than in White patients, despite biologic medications being very efficacious for treatment of psoriasis.^1,9,10

The Comparison

A Elbow and forearm with erythematous, well-demarcated, pink plaques with mild micaceous scale in a 42-year-old White woman.

B Elbow and forearm with violaceous, well-demarcated plaques with micaceous scale and hyperpigmented patches around the active plaques in a 58-year-old Black man.

Epidemiology
Psoriasis prevalence in the United States has been estimated at 3.7%.^1-3 If broken down by race or ethnicity, the prevalence of psoriasis varies: 2.5% to 3.7% in White adults^1-4; 1.3% to 2% in Black adults^1-4; 1.6% in Hispanics/ other adults^1-3; 1% in children overall; 0.29% in White children_^1,5; and 0.06% in Black children.^1,5

Key clinical features in people with darker skin tones include:

• plaques that may appear more violaceous in color instead of pink or erythematous
• higher body surface area of involvement4 and thicker, more scaly plaques⁶
• increased likelihood of postinflammatory hyperpigmentation (PIH).

Worth noting
Although individuals of all skin tones may experience the psychosocial impact of psoriasis, quality-of-life measures have been found to be worse in those with skin of color (SOC) compared to White patients.^1,4 This may be due to the lingering PIH and hypopigmentation that occurs even after inflammatory plaques are treated. Of course, lack of access to care contributes to greater disease burden and more devastating psychological impact.

Health disparity highlight
Psoriasis may be underreported and underdiagnosed in individuals with SOC, as factors contributing to health care disparities may play a role, such as access to health care in general,^1,7 and access to clinicians proficient in diagnosing cutaneous diseases in SOC may be delayed.⁸

Biologic medications are used less often in Black patients than in White patients, despite biologic medications being very efficacious for treatment of psoriasis.^1,9,10

The Comparison

A Elbow and forearm with erythematous, well-demarcated, pink plaques with mild micaceous scale in a 42-year-old White woman.

B Elbow and forearm with violaceous, well-demarcated plaques with micaceous scale and hyperpigmented patches around the active plaques in a 58-year-old Black man.

Epidemiology
Psoriasis prevalence in the United States has been estimated at 3.7%.^1-3 If broken down by race or ethnicity, the prevalence of psoriasis varies: 2.5% to 3.7% in White adults^1-4; 1.3% to 2% in Black adults^1-4; 1.6% in Hispanics/ other adults^1-3; 1% in children overall; 0.29% in White children_^1,5; and 0.06% in Black children.^1,5

Key clinical features in people with darker skin tones include:

• plaques that may appear more violaceous in color instead of pink or erythematous
• higher body surface area of involvement4 and thicker, more scaly plaques⁶
• increased likelihood of postinflammatory hyperpigmentation (PIH).

Worth noting
Although individuals of all skin tones may experience the psychosocial impact of psoriasis, quality-of-life measures have been found to be worse in those with skin of color (SOC) compared to White patients.^1,4 This may be due to the lingering PIH and hypopigmentation that occurs even after inflammatory plaques are treated. Of course, lack of access to care contributes to greater disease burden and more devastating psychological impact.

Health disparity highlight
Psoriasis may be underreported and underdiagnosed in individuals with SOC, as factors contributing to health care disparities may play a role, such as access to health care in general,^1,7 and access to clinicians proficient in diagnosing cutaneous diseases in SOC may be delayed.⁸

Biologic medications are used less often in Black patients than in White patients, despite biologic medications being very efficacious for treatment of psoriasis.^1,9,10

People taking methotrexate had low antibody responses after the first dose of the Pfizer-BioNTech mRNA COVID-19 vaccine, but did show evidence of T-cell–mediated immune responses, findings from a small study show.

The common immunosuppressant has previously been linked to poor antibody responses to mRNA COVID-19 vaccines, but this appears to be the first study to look at T-cell responses in people taking methotrexate.

The study findings were presented online July 11 at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published in The Lancet Rheumatology.

“These findings indicate that seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression, and caution against routine use of seroconversion data in isolation in clinical practice,” Satveer K. Mahil, MBBChir, PhD, from St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust, London, and colleagues wrote.

“When taking into account functional humoral immunity and T-cell responses, our data suggest that targeted biologics do not impair vaccine responses and provide some reassurance to this vulnerable population,” they wrote. “Notably, although methotrexate attenuated humoral immunity, cellular responses were preserved.”

Dr. Mahil and colleagues assessed 84 consecutive patients from a psoriasis specialist clinic that serves London and southeast England. Median age of the cohort was 43 years, and 85% were White. All had a confirmed psoriasis diagnosis, received the first dose of the Pfizer-BioNTech COVID-19 vaccine, and were taking either methotrexate (17 patients) or a targeted biologic (27 were taking a tumor necrosis factor inhibitor, 15 an interleukin-17 inhibitor, and 25 an IL-23 inhibitor). In addition, 17 healthy patients not receiving immunosuppression therapy who received the Pfizer-BioNTech vaccine served as the control group.

Four weeks after the study participants received their first dose of the vaccine, 78% of the immunosuppressed patients underwent seroconversion – producing measurable antibodies – as did 100% of the control group. Patients taking methotrexate had the lowest seroconversion rate at 47%, compared with 79% with TNF inhibitors, 83% with IL-23 inhibitors, and 100% with IL-17 inhibitors.

Participants taking methotrexate also had lower neutralizing activity against SARS-CoV-2 than control subjects and those taking a targeted biologic, who had similar levels of neutralizing activity.

All participants had low neutralizing titers against the alpha (B.1.1.7) variant.

The researchers also assessed cellular immunity, “defined as the presence of T cells secreting interferon-gamma, IL-2, or IL-21 in response to stimulation with two peptide pools spanning the entire length of the SARS-CoV-2 spike glycoprotein.”

A T-cell response was seen in 84% of participants taking immunosuppressants, including 93% of those in the methotrexate group and 69% of control subjects.

‘Some protection is better than none’

These findings regarding antibodies match what has been seen in other research, said Ignacio Sanz, MD, director of the Lowance Center for Human Immunology at Emory University, Atlanta.

It would be helpful to see antibody responses after the second doses, he added. Those data will be reported later, according to Dr. Mahil and colleagues.

“The authors make the valid point that T-cell immunity should also be measured. The information is meaningful and supports the idea that there could be protection still provided,” Dr. Sanz said in an interview, adding that it would have been helpful to see CD8 T-cell response as well.

“My message to patients, still, is that some protection is better than none, and that, indeed, protection may be afforded in different ways, including T-cell immunity, which, to the extent tested, seems to be induced,” he said. But discussion of B cells independent of their role in producing antibodies is missing.

“When it comes to B-cell responses, antibodies are the easier and more direct measurement. However, it is perfectly possible that the vaccine may fail to induce high antibody titers and still generate good B-cell immunity,” in the same way virus-specific memory B cells do, he explained. “They would not directly produce antibodies, yet they would be available for a good and quick response in the case of subsequent encounter with the virus and, incidentally, in the case of a booster dose. It is possible that the generation of antibody-producing plasma cells might be uncoupled from the generation of memory B cells.”
 

Temporarily stopping methotrexate

It is well known that methotrexate impairs humoral responses to influenza and pneumococcal vaccines, write Caoilfhionn M. Connolly, MD, and Julie J. Paik, MD, both from the Johns Hopkins University, Baltimore, in an accompanying comment.

Research has also shown that temporarily stopping methotrexate therapy for 2 weeks enhances response to the flu vaccine in patients with rheumatoid arthritis, which prompted the American College of Rheumatology to recommended temporary interruption of methotrexate for 1 week after each dose of the COVID-19 vaccine, the pair notes.

“Although it is encouraging that cellular responses appear to be preserved even in patients with poor humoral responses, these findings are not consistent across study groups,” Dr. Connolly and Dr. Paik explained. “During this period of clinical uncertainty, patients might remain vulnerable, especially after the first dose, and should engage in risk mitigation strategies.”

Mild adverse events after vaccination were reported by 75% of the immunosuppressed patients – most commonly injection-site pain, headache, and fatigue – and by 94% of control subjects. No participants reported moderate or severe adverse effects.

However, 11% of immunosuppressed patients reported a worsening of psoriasis symptoms after vaccination.

This research was funded by the U.K. National Institute for Health Research. Dr. Mahil has received departmental income from AbbVie, Celgene, Eli Lilly, Janssen-Cilag, Novartis, Sano, and UCB unrelated to this study. Seven other authors have relationships with a wide range of pharmaceutical and other companies. Dr. Sanz, Dr. Connolly, and Dr. Paik disclosed no relevant financial relationships.

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

People taking methotrexate had low antibody responses after the first dose of the Pfizer-BioNTech mRNA COVID-19 vaccine, but did show evidence of T-cell–mediated immune responses, findings from a small study show.

The common immunosuppressant has previously been linked to poor antibody responses to mRNA COVID-19 vaccines, but this appears to be the first study to look at T-cell responses in people taking methotrexate.

The study findings were presented online July 11 at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published in The Lancet Rheumatology.

“These findings indicate that seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression, and caution against routine use of seroconversion data in isolation in clinical practice,” Satveer K. Mahil, MBBChir, PhD, from St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust, London, and colleagues wrote.

“When taking into account functional humoral immunity and T-cell responses, our data suggest that targeted biologics do not impair vaccine responses and provide some reassurance to this vulnerable population,” they wrote. “Notably, although methotrexate attenuated humoral immunity, cellular responses were preserved.”

Dr. Mahil and colleagues assessed 84 consecutive patients from a psoriasis specialist clinic that serves London and southeast England. Median age of the cohort was 43 years, and 85% were White. All had a confirmed psoriasis diagnosis, received the first dose of the Pfizer-BioNTech COVID-19 vaccine, and were taking either methotrexate (17 patients) or a targeted biologic (27 were taking a tumor necrosis factor inhibitor, 15 an interleukin-17 inhibitor, and 25 an IL-23 inhibitor). In addition, 17 healthy patients not receiving immunosuppression therapy who received the Pfizer-BioNTech vaccine served as the control group.

Four weeks after the study participants received their first dose of the vaccine, 78% of the immunosuppressed patients underwent seroconversion – producing measurable antibodies – as did 100% of the control group. Patients taking methotrexate had the lowest seroconversion rate at 47%, compared with 79% with TNF inhibitors, 83% with IL-23 inhibitors, and 100% with IL-17 inhibitors.

Participants taking methotrexate also had lower neutralizing activity against SARS-CoV-2 than control subjects and those taking a targeted biologic, who had similar levels of neutralizing activity.

All participants had low neutralizing titers against the alpha (B.1.1.7) variant.

The researchers also assessed cellular immunity, “defined as the presence of T cells secreting interferon-gamma, IL-2, or IL-21 in response to stimulation with two peptide pools spanning the entire length of the SARS-CoV-2 spike glycoprotein.”

A T-cell response was seen in 84% of participants taking immunosuppressants, including 93% of those in the methotrexate group and 69% of control subjects.

‘Some protection is better than none’

These findings regarding antibodies match what has been seen in other research, said Ignacio Sanz, MD, director of the Lowance Center for Human Immunology at Emory University, Atlanta.

It would be helpful to see antibody responses after the second doses, he added. Those data will be reported later, according to Dr. Mahil and colleagues.

“The authors make the valid point that T-cell immunity should also be measured. The information is meaningful and supports the idea that there could be protection still provided,” Dr. Sanz said in an interview, adding that it would have been helpful to see CD8 T-cell response as well.

“My message to patients, still, is that some protection is better than none, and that, indeed, protection may be afforded in different ways, including T-cell immunity, which, to the extent tested, seems to be induced,” he said. But discussion of B cells independent of their role in producing antibodies is missing.

“When it comes to B-cell responses, antibodies are the easier and more direct measurement. However, it is perfectly possible that the vaccine may fail to induce high antibody titers and still generate good B-cell immunity,” in the same way virus-specific memory B cells do, he explained. “They would not directly produce antibodies, yet they would be available for a good and quick response in the case of subsequent encounter with the virus and, incidentally, in the case of a booster dose. It is possible that the generation of antibody-producing plasma cells might be uncoupled from the generation of memory B cells.”
 

Temporarily stopping methotrexate

It is well known that methotrexate impairs humoral responses to influenza and pneumococcal vaccines, write Caoilfhionn M. Connolly, MD, and Julie J. Paik, MD, both from the Johns Hopkins University, Baltimore, in an accompanying comment.

Research has also shown that temporarily stopping methotrexate therapy for 2 weeks enhances response to the flu vaccine in patients with rheumatoid arthritis, which prompted the American College of Rheumatology to recommended temporary interruption of methotrexate for 1 week after each dose of the COVID-19 vaccine, the pair notes.

“Although it is encouraging that cellular responses appear to be preserved even in patients with poor humoral responses, these findings are not consistent across study groups,” Dr. Connolly and Dr. Paik explained. “During this period of clinical uncertainty, patients might remain vulnerable, especially after the first dose, and should engage in risk mitigation strategies.”

Mild adverse events after vaccination were reported by 75% of the immunosuppressed patients – most commonly injection-site pain, headache, and fatigue – and by 94% of control subjects. No participants reported moderate or severe adverse effects.

However, 11% of immunosuppressed patients reported a worsening of psoriasis symptoms after vaccination.

This research was funded by the U.K. National Institute for Health Research. Dr. Mahil has received departmental income from AbbVie, Celgene, Eli Lilly, Janssen-Cilag, Novartis, Sano, and UCB unrelated to this study. Seven other authors have relationships with a wide range of pharmaceutical and other companies. Dr. Sanz, Dr. Connolly, and Dr. Paik disclosed no relevant financial relationships.

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

People taking methotrexate had low antibody responses after the first dose of the Pfizer-BioNTech mRNA COVID-19 vaccine, but did show evidence of T-cell–mediated immune responses, findings from a small study show.

The common immunosuppressant has previously been linked to poor antibody responses to mRNA COVID-19 vaccines, but this appears to be the first study to look at T-cell responses in people taking methotrexate.

The study findings were presented online July 11 at the 31st European Congress of Clinical Microbiology & Infectious Diseases and published in The Lancet Rheumatology.

“These findings indicate that seroconversion alone might not adequately reflect vaccine immunogenicity in individuals with immune-mediated inflammatory diseases receiving therapeutic immunosuppression, and caution against routine use of seroconversion data in isolation in clinical practice,” Satveer K. Mahil, MBBChir, PhD, from St. John’s Institute of Dermatology, Guy’s and St. Thomas’ NHS Foundation Trust, London, and colleagues wrote.

“When taking into account functional humoral immunity and T-cell responses, our data suggest that targeted biologics do not impair vaccine responses and provide some reassurance to this vulnerable population,” they wrote. “Notably, although methotrexate attenuated humoral immunity, cellular responses were preserved.”

Dr. Mahil and colleagues assessed 84 consecutive patients from a psoriasis specialist clinic that serves London and southeast England. Median age of the cohort was 43 years, and 85% were White. All had a confirmed psoriasis diagnosis, received the first dose of the Pfizer-BioNTech COVID-19 vaccine, and were taking either methotrexate (17 patients) or a targeted biologic (27 were taking a tumor necrosis factor inhibitor, 15 an interleukin-17 inhibitor, and 25 an IL-23 inhibitor). In addition, 17 healthy patients not receiving immunosuppression therapy who received the Pfizer-BioNTech vaccine served as the control group.

Four weeks after the study participants received their first dose of the vaccine, 78% of the immunosuppressed patients underwent seroconversion – producing measurable antibodies – as did 100% of the control group. Patients taking methotrexate had the lowest seroconversion rate at 47%, compared with 79% with TNF inhibitors, 83% with IL-23 inhibitors, and 100% with IL-17 inhibitors.

Participants taking methotrexate also had lower neutralizing activity against SARS-CoV-2 than control subjects and those taking a targeted biologic, who had similar levels of neutralizing activity.

All participants had low neutralizing titers against the alpha (B.1.1.7) variant.

The researchers also assessed cellular immunity, “defined as the presence of T cells secreting interferon-gamma, IL-2, or IL-21 in response to stimulation with two peptide pools spanning the entire length of the SARS-CoV-2 spike glycoprotein.”

A T-cell response was seen in 84% of participants taking immunosuppressants, including 93% of those in the methotrexate group and 69% of control subjects.

‘Some protection is better than none’

These findings regarding antibodies match what has been seen in other research, said Ignacio Sanz, MD, director of the Lowance Center for Human Immunology at Emory University, Atlanta.

It would be helpful to see antibody responses after the second doses, he added. Those data will be reported later, according to Dr. Mahil and colleagues.

“The authors make the valid point that T-cell immunity should also be measured. The information is meaningful and supports the idea that there could be protection still provided,” Dr. Sanz said in an interview, adding that it would have been helpful to see CD8 T-cell response as well.

“My message to patients, still, is that some protection is better than none, and that, indeed, protection may be afforded in different ways, including T-cell immunity, which, to the extent tested, seems to be induced,” he said. But discussion of B cells independent of their role in producing antibodies is missing.

“When it comes to B-cell responses, antibodies are the easier and more direct measurement. However, it is perfectly possible that the vaccine may fail to induce high antibody titers and still generate good B-cell immunity,” in the same way virus-specific memory B cells do, he explained. “They would not directly produce antibodies, yet they would be available for a good and quick response in the case of subsequent encounter with the virus and, incidentally, in the case of a booster dose. It is possible that the generation of antibody-producing plasma cells might be uncoupled from the generation of memory B cells.”
 

Temporarily stopping methotrexate

It is well known that methotrexate impairs humoral responses to influenza and pneumococcal vaccines, write Caoilfhionn M. Connolly, MD, and Julie J. Paik, MD, both from the Johns Hopkins University, Baltimore, in an accompanying comment.

Research has also shown that temporarily stopping methotrexate therapy for 2 weeks enhances response to the flu vaccine in patients with rheumatoid arthritis, which prompted the American College of Rheumatology to recommended temporary interruption of methotrexate for 1 week after each dose of the COVID-19 vaccine, the pair notes.

“Although it is encouraging that cellular responses appear to be preserved even in patients with poor humoral responses, these findings are not consistent across study groups,” Dr. Connolly and Dr. Paik explained. “During this period of clinical uncertainty, patients might remain vulnerable, especially after the first dose, and should engage in risk mitigation strategies.”

Mild adverse events after vaccination were reported by 75% of the immunosuppressed patients – most commonly injection-site pain, headache, and fatigue – and by 94% of control subjects. No participants reported moderate or severe adverse effects.

However, 11% of immunosuppressed patients reported a worsening of psoriasis symptoms after vaccination.

This research was funded by the U.K. National Institute for Health Research. Dr. Mahil has received departmental income from AbbVie, Celgene, Eli Lilly, Janssen-Cilag, Novartis, Sano, and UCB unrelated to this study. Seven other authors have relationships with a wide range of pharmaceutical and other companies. Dr. Sanz, Dr. Connolly, and Dr. Paik disclosed no relevant financial relationships.

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

To the Editor:

Etanercept is an immune-modulating drug used for the treatment of a variety of diseases including psoriasis, rheumatoid arthritis, and ankylosing spondylitis. It is an anti–tumor necrosis factor (TNF) fusion protein consisting of an extracellular domain of the p75 TNF receptor and the Fc portion of human IgG.¹ Etanercept is well known for its immunosuppressive side effects. A handful of case reports have provided evidence of squamous cell cancers in the setting of etanercept therapy. The most comprehensive description was a case series by Brewer et al² describing 4 patients with squamous cell carcinoma (SCC) that developed 1 to 17 months after the initiation of etanercept therapy. We present a case of a patient diagnosed with psoriasis and concomitant porokeratosis who developed multiple SCCs and squamous proliferations after initiation of etanercept therapy.

A 66-year-old man was referred to our clinic for treatment of psoriasis, as noted on a biopsy of the right ankle diagnosed several years prior. He was being treated with etanercept 50 mg twice weekly. Other treatments included calcipotriene–betamethasone dipropionate, salicylic acid gel, intralesional triamcinolone, clobetasol, and urea 40%. Physical examination revealed multiple erythematous tender nodules with hyperkeratotic scale distributed on the right arm and leg (Figure 1) that were concerning for SCC. Biopsies from 6 lesions revealed multiple SCC/keratoacanthomas (KAs) with verrucous features (Figure 2). Primers for human papillomavirus (HPV) 6, 11, 16, 18, 31, 33, and 51 were all negative. At that time, etanercept was discontinued. The patient was referred for Mohs micrographic surgery and underwent excision of several SCC lesions including an approximately 7-cm SCC on the right ankle (Figure 1B). Positron emission tomography/computed tomography found hypermetabolic lymphadenopathy. A follow-up biopsy of the inguinal nodes identified no malignant cells. Given their multiplicity, the patient was initiated on a prolonged course of a retinoid with acitretin 35 mg daily. The clearance of the large 7-cm lesion with a single stage of Mohs micrographic surgery directed suspicion to a pseudoepitheliomatous or HPV-induced cause for the lesions. Rereview of the original 6 biopsies indicated 1 definitive SCC on the right wrist, 2 KAs, and 3 that were most consistent with verruca vulgaris. At 1-year follow-up, most of the hyperkeratotic lesions had resolved with continued acitretin. Baseline porokeratosis lesions that were abundantly present on the arms and legs resolved by 1-year follow-up (Figure 3A).

The link between classic porokeratosis and the development of squamous cell proliferations is well established. Ninomiya et al³ noted a possible mechanism of p53 overexpression in the epidermis of porokeratotic lesions that may make the lesions particularly susceptible to the development of immunosuppression-induced SCC. Etanercept is an immune-modulating drug with well-known immunosuppressive side effects including reactivation of HPV as well as the development of SCCs.

Our patient initially was diagnosed with psoriasis and etanercept was initiated. The presence of coexistent porokeratosis likely predisposed him to etanercept-induced squamous proliferations including 2 SCCs and verrucous lesions, with histologic features suggesting SCC/KA. Histopathology revealed a cornoid lamella in SCC (Figure 3B), suggesting development of malignancy within epithelial clones, as noted by Lee et al.⁴

Targeted systemic therapies may lead to the formation of SCCs. The association between epidermal growth factor receptor (EGFR) kinase inhibitors and SCC formation is well known. For instance, sorafenib—a multikinase inhibitor that is downstream in the EGFR pathway—has been noted to induce epidermal growths including KAs and SCCs.⁵ There has been no definitive causal relationship identified between the development of SCC and TNF-α inhibitors. It has been suggested that perhaps there is an unmasking effect, as subclinical SCC manifests after TNF-α inhibition that leads to SCC development. Discontinuation of etanercept and resolution of lesions highlights a potential role of TNF-α inhibition and tumorigenesis of SCCs, especially in the background of porokeratosis. Vigilance for development of immunosuppression-induced malignancy, especially squamous cell proliferations, has become exceedingly important with exponentially increasing use of biologic therapies in medicine.

To the Editor:

Etanercept is an immune-modulating drug used for the treatment of a variety of diseases including psoriasis, rheumatoid arthritis, and ankylosing spondylitis. It is an anti–tumor necrosis factor (TNF) fusion protein consisting of an extracellular domain of the p75 TNF receptor and the Fc portion of human IgG.¹ Etanercept is well known for its immunosuppressive side effects. A handful of case reports have provided evidence of squamous cell cancers in the setting of etanercept therapy. The most comprehensive description was a case series by Brewer et al² describing 4 patients with squamous cell carcinoma (SCC) that developed 1 to 17 months after the initiation of etanercept therapy. We present a case of a patient diagnosed with psoriasis and concomitant porokeratosis who developed multiple SCCs and squamous proliferations after initiation of etanercept therapy.

A 66-year-old man was referred to our clinic for treatment of psoriasis, as noted on a biopsy of the right ankle diagnosed several years prior. He was being treated with etanercept 50 mg twice weekly. Other treatments included calcipotriene–betamethasone dipropionate, salicylic acid gel, intralesional triamcinolone, clobetasol, and urea 40%. Physical examination revealed multiple erythematous tender nodules with hyperkeratotic scale distributed on the right arm and leg (Figure 1) that were concerning for SCC. Biopsies from 6 lesions revealed multiple SCC/keratoacanthomas (KAs) with verrucous features (Figure 2). Primers for human papillomavirus (HPV) 6, 11, 16, 18, 31, 33, and 51 were all negative. At that time, etanercept was discontinued. The patient was referred for Mohs micrographic surgery and underwent excision of several SCC lesions including an approximately 7-cm SCC on the right ankle (Figure 1B). Positron emission tomography/computed tomography found hypermetabolic lymphadenopathy. A follow-up biopsy of the inguinal nodes identified no malignant cells. Given their multiplicity, the patient was initiated on a prolonged course of a retinoid with acitretin 35 mg daily. The clearance of the large 7-cm lesion with a single stage of Mohs micrographic surgery directed suspicion to a pseudoepitheliomatous or HPV-induced cause for the lesions. Rereview of the original 6 biopsies indicated 1 definitive SCC on the right wrist, 2 KAs, and 3 that were most consistent with verruca vulgaris. At 1-year follow-up, most of the hyperkeratotic lesions had resolved with continued acitretin. Baseline porokeratosis lesions that were abundantly present on the arms and legs resolved by 1-year follow-up (Figure 3A).

The link between classic porokeratosis and the development of squamous cell proliferations is well established. Ninomiya et al³ noted a possible mechanism of p53 overexpression in the epidermis of porokeratotic lesions that may make the lesions particularly susceptible to the development of immunosuppression-induced SCC. Etanercept is an immune-modulating drug with well-known immunosuppressive side effects including reactivation of HPV as well as the development of SCCs.

Our patient initially was diagnosed with psoriasis and etanercept was initiated. The presence of coexistent porokeratosis likely predisposed him to etanercept-induced squamous proliferations including 2 SCCs and verrucous lesions, with histologic features suggesting SCC/KA. Histopathology revealed a cornoid lamella in SCC (Figure 3B), suggesting development of malignancy within epithelial clones, as noted by Lee et al.⁴

Targeted systemic therapies may lead to the formation of SCCs. The association between epidermal growth factor receptor (EGFR) kinase inhibitors and SCC formation is well known. For instance, sorafenib—a multikinase inhibitor that is downstream in the EGFR pathway—has been noted to induce epidermal growths including KAs and SCCs.⁵ There has been no definitive causal relationship identified between the development of SCC and TNF-α inhibitors. It has been suggested that perhaps there is an unmasking effect, as subclinical SCC manifests after TNF-α inhibition that leads to SCC development. Discontinuation of etanercept and resolution of lesions highlights a potential role of TNF-α inhibition and tumorigenesis of SCCs, especially in the background of porokeratosis. Vigilance for development of immunosuppression-induced malignancy, especially squamous cell proliferations, has become exceedingly important with exponentially increasing use of biologic therapies in medicine.

To the Editor:

Etanercept is an immune-modulating drug used for the treatment of a variety of diseases including psoriasis, rheumatoid arthritis, and ankylosing spondylitis. It is an anti–tumor necrosis factor (TNF) fusion protein consisting of an extracellular domain of the p75 TNF receptor and the Fc portion of human IgG.¹ Etanercept is well known for its immunosuppressive side effects. A handful of case reports have provided evidence of squamous cell cancers in the setting of etanercept therapy. The most comprehensive description was a case series by Brewer et al² describing 4 patients with squamous cell carcinoma (SCC) that developed 1 to 17 months after the initiation of etanercept therapy. We present a case of a patient diagnosed with psoriasis and concomitant porokeratosis who developed multiple SCCs and squamous proliferations after initiation of etanercept therapy.

A 66-year-old man was referred to our clinic for treatment of psoriasis, as noted on a biopsy of the right ankle diagnosed several years prior. He was being treated with etanercept 50 mg twice weekly. Other treatments included calcipotriene–betamethasone dipropionate, salicylic acid gel, intralesional triamcinolone, clobetasol, and urea 40%. Physical examination revealed multiple erythematous tender nodules with hyperkeratotic scale distributed on the right arm and leg (Figure 1) that were concerning for SCC. Biopsies from 6 lesions revealed multiple SCC/keratoacanthomas (KAs) with verrucous features (Figure 2). Primers for human papillomavirus (HPV) 6, 11, 16, 18, 31, 33, and 51 were all negative. At that time, etanercept was discontinued. The patient was referred for Mohs micrographic surgery and underwent excision of several SCC lesions including an approximately 7-cm SCC on the right ankle (Figure 1B). Positron emission tomography/computed tomography found hypermetabolic lymphadenopathy. A follow-up biopsy of the inguinal nodes identified no malignant cells. Given their multiplicity, the patient was initiated on a prolonged course of a retinoid with acitretin 35 mg daily. The clearance of the large 7-cm lesion with a single stage of Mohs micrographic surgery directed suspicion to a pseudoepitheliomatous or HPV-induced cause for the lesions. Rereview of the original 6 biopsies indicated 1 definitive SCC on the right wrist, 2 KAs, and 3 that were most consistent with verruca vulgaris. At 1-year follow-up, most of the hyperkeratotic lesions had resolved with continued acitretin. Baseline porokeratosis lesions that were abundantly present on the arms and legs resolved by 1-year follow-up (Figure 3A).

The link between classic porokeratosis and the development of squamous cell proliferations is well established. Ninomiya et al³ noted a possible mechanism of p53 overexpression in the epidermis of porokeratotic lesions that may make the lesions particularly susceptible to the development of immunosuppression-induced SCC. Etanercept is an immune-modulating drug with well-known immunosuppressive side effects including reactivation of HPV as well as the development of SCCs.

Our patient initially was diagnosed with psoriasis and etanercept was initiated. The presence of coexistent porokeratosis likely predisposed him to etanercept-induced squamous proliferations including 2 SCCs and verrucous lesions, with histologic features suggesting SCC/KA. Histopathology revealed a cornoid lamella in SCC (Figure 3B), suggesting development of malignancy within epithelial clones, as noted by Lee et al.⁴

Targeted systemic therapies may lead to the formation of SCCs. The association between epidermal growth factor receptor (EGFR) kinase inhibitors and SCC formation is well known. For instance, sorafenib—a multikinase inhibitor that is downstream in the EGFR pathway—has been noted to induce epidermal growths including KAs and SCCs.⁵ There has been no definitive causal relationship identified between the development of SCC and TNF-α inhibitors. It has been suggested that perhaps there is an unmasking effect, as subclinical SCC manifests after TNF-α inhibition that leads to SCC development. Discontinuation of etanercept and resolution of lesions highlights a potential role of TNF-α inhibition and tumorigenesis of SCCs, especially in the background of porokeratosis. Vigilance for development of immunosuppression-induced malignancy, especially squamous cell proliferations, has become exceedingly important with exponentially increasing use of biologic therapies in medicine.

Obesity, atopic dermatitis, psychiatric disease, and arthritis are the most common comorbidities among infants, children, and adolescents with psoriasis, while predictors of moderate to severe disease include morphology, non-White race, and culture-confirmed infection.

Those are among the key findings from a retrospective analysis of pediatric psoriasis patients who were seen at the University of California, San Francisco, over a 24-year period.

“Overall, our data support prior findings of age- and sex-based differences in location and morphology and presents new information demonstrating associations with severity,” presenting study author Carmel Aghdasi said during the annual meeting of the Society for Pediatric Dermatology. “We provide evidence of the increased use of systemic and biologic therapies over time, an important step in ensuring pediatric patients are adequately treated.”

To characterize the demographics, clinical features, comorbidities, and treatments, and to determine predictors of severity and changes in treatment patterns over 2 decades in a large cohort of pediatric psoriasis patients, Ms. Aghdasi, a 4th-year medical student at the University of California, San Francisco, and colleagues retrospectively evaluated the records of 754 pediatric patients up to 18 years of age who were seen at UCSF for psoriasis from 1997 to 2021. They collected demographic, clinical, familial, comorbidity, and treatment data and divided the cohort into two groups by date of last visit.

Group 1 consisted of 332 patients whose last visit was between 2001 and 2011, while the second group included 422 patients whose last visit was between 2012 and 2021. The researchers also divided the cohort into three age groups: infants (0-2 years of age), children (3-12 years of age), and adolescents (13-18 years of age).

Slightly more than half of the patients (55%) were female and 67% presented between ages 3 and 12. (Seventy-four patients were in the youngest category, 0-2 years, when they presented.) The average age of disease onset was 7 years, the average age at presentation to pediatric dermatology was 8.8 years, and 37% of the total cohort were overweight or obese. The top four comorbidities were being overweight or obese (37%), followed by atopic dermatitis (19%), psychiatric disease (7%), and arthritis (4%).

Plaque was the most common morphology (56%), while the most common sites of involvement were the head and neck (69%), extremities (61%), and trunk (44%). About half of the cohort (51%) had mild disease, 15% had culture-confirmed infections (9% had Streptococcal infections), and 66% of patients reported itch as a symptom.

The researchers observed that inverse psoriasis was significantly more common in infants and decreased with age. Anogenital involvement was more common in males and in those aged 0-2, while head and neck involvement was more common in females. Nail involvement was more common in childhood.

Topical therapy was the most common treatment overall and by far the most common among those in the 0-2 age category. “Overall, phototherapy was used in childhood and adolescents but almost never in infancy,” Ms. Aghdasi said. “Looking at changes in systemic treatment over time, conventional systemic use increased in infants and children and decreased in adolescents. Biologic use increased in all ages, most notably in children aged 3-12 years old.”

Multivariate regression analyses revealed that the following independent variables predicted moderate to severe psoriasis: adolescent age (adjusted odds ratio, 1.9; P = .03), guttate morphology (aOR, 2.2; P = .006), plaque and guttate morphology (aOR, 7.6; P less than .001), pustular or erythrodermic morphology (aOR, 5; P = .003), culture-confirmed infection (aOR, 2; P = .007), Black race (aOR, 3.3; P = .007), Asian race (aOR, 1.8; P = .04, and Hispanic race (aOR, 1.9; P = .03).

“Further analysis is needed to elucidate the influence of race on severity and of the clinical utility of infection as a marker of severity,” Ms. Aghdasi said. “Interestingly, we did not find that obesity was a marker of severity in our cohort.”

In an interview, senior study author Kelly M. Cordoro, MD, professor of dermatology and pediatrics at UCSF, noted that this finding conflicts with prior studies showing an association between obesity and severe psoriasis in children.

[email protected]

Obesity, atopic dermatitis, psychiatric disease, and arthritis are the most common comorbidities among infants, children, and adolescents with psoriasis, while predictors of moderate to severe disease include morphology, non-White race, and culture-confirmed infection.

Those are among the key findings from a retrospective analysis of pediatric psoriasis patients who were seen at the University of California, San Francisco, over a 24-year period.

“Overall, our data support prior findings of age- and sex-based differences in location and morphology and presents new information demonstrating associations with severity,” presenting study author Carmel Aghdasi said during the annual meeting of the Society for Pediatric Dermatology. “We provide evidence of the increased use of systemic and biologic therapies over time, an important step in ensuring pediatric patients are adequately treated.”

To characterize the demographics, clinical features, comorbidities, and treatments, and to determine predictors of severity and changes in treatment patterns over 2 decades in a large cohort of pediatric psoriasis patients, Ms. Aghdasi, a 4th-year medical student at the University of California, San Francisco, and colleagues retrospectively evaluated the records of 754 pediatric patients up to 18 years of age who were seen at UCSF for psoriasis from 1997 to 2021. They collected demographic, clinical, familial, comorbidity, and treatment data and divided the cohort into two groups by date of last visit.

Group 1 consisted of 332 patients whose last visit was between 2001 and 2011, while the second group included 422 patients whose last visit was between 2012 and 2021. The researchers also divided the cohort into three age groups: infants (0-2 years of age), children (3-12 years of age), and adolescents (13-18 years of age).

Slightly more than half of the patients (55%) were female and 67% presented between ages 3 and 12. (Seventy-four patients were in the youngest category, 0-2 years, when they presented.) The average age of disease onset was 7 years, the average age at presentation to pediatric dermatology was 8.8 years, and 37% of the total cohort were overweight or obese. The top four comorbidities were being overweight or obese (37%), followed by atopic dermatitis (19%), psychiatric disease (7%), and arthritis (4%).

Plaque was the most common morphology (56%), while the most common sites of involvement were the head and neck (69%), extremities (61%), and trunk (44%). About half of the cohort (51%) had mild disease, 15% had culture-confirmed infections (9% had Streptococcal infections), and 66% of patients reported itch as a symptom.

The researchers observed that inverse psoriasis was significantly more common in infants and decreased with age. Anogenital involvement was more common in males and in those aged 0-2, while head and neck involvement was more common in females. Nail involvement was more common in childhood.

Topical therapy was the most common treatment overall and by far the most common among those in the 0-2 age category. “Overall, phototherapy was used in childhood and adolescents but almost never in infancy,” Ms. Aghdasi said. “Looking at changes in systemic treatment over time, conventional systemic use increased in infants and children and decreased in adolescents. Biologic use increased in all ages, most notably in children aged 3-12 years old.”

Multivariate regression analyses revealed that the following independent variables predicted moderate to severe psoriasis: adolescent age (adjusted odds ratio, 1.9; P = .03), guttate morphology (aOR, 2.2; P = .006), plaque and guttate morphology (aOR, 7.6; P less than .001), pustular or erythrodermic morphology (aOR, 5; P = .003), culture-confirmed infection (aOR, 2; P = .007), Black race (aOR, 3.3; P = .007), Asian race (aOR, 1.8; P = .04, and Hispanic race (aOR, 1.9; P = .03).

“Further analysis is needed to elucidate the influence of race on severity and of the clinical utility of infection as a marker of severity,” Ms. Aghdasi said. “Interestingly, we did not find that obesity was a marker of severity in our cohort.”

In an interview, senior study author Kelly M. Cordoro, MD, professor of dermatology and pediatrics at UCSF, noted that this finding conflicts with prior studies showing an association between obesity and severe psoriasis in children.

[email protected]

Obesity, atopic dermatitis, psychiatric disease, and arthritis are the most common comorbidities among infants, children, and adolescents with psoriasis, while predictors of moderate to severe disease include morphology, non-White race, and culture-confirmed infection.

Those are among the key findings from a retrospective analysis of pediatric psoriasis patients who were seen at the University of California, San Francisco, over a 24-year period.

“Overall, our data support prior findings of age- and sex-based differences in location and morphology and presents new information demonstrating associations with severity,” presenting study author Carmel Aghdasi said during the annual meeting of the Society for Pediatric Dermatology. “We provide evidence of the increased use of systemic and biologic therapies over time, an important step in ensuring pediatric patients are adequately treated.”

To characterize the demographics, clinical features, comorbidities, and treatments, and to determine predictors of severity and changes in treatment patterns over 2 decades in a large cohort of pediatric psoriasis patients, Ms. Aghdasi, a 4th-year medical student at the University of California, San Francisco, and colleagues retrospectively evaluated the records of 754 pediatric patients up to 18 years of age who were seen at UCSF for psoriasis from 1997 to 2021. They collected demographic, clinical, familial, comorbidity, and treatment data and divided the cohort into two groups by date of last visit.

Group 1 consisted of 332 patients whose last visit was between 2001 and 2011, while the second group included 422 patients whose last visit was between 2012 and 2021. The researchers also divided the cohort into three age groups: infants (0-2 years of age), children (3-12 years of age), and adolescents (13-18 years of age).

Slightly more than half of the patients (55%) were female and 67% presented between ages 3 and 12. (Seventy-four patients were in the youngest category, 0-2 years, when they presented.) The average age of disease onset was 7 years, the average age at presentation to pediatric dermatology was 8.8 years, and 37% of the total cohort were overweight or obese. The top four comorbidities were being overweight or obese (37%), followed by atopic dermatitis (19%), psychiatric disease (7%), and arthritis (4%).

Plaque was the most common morphology (56%), while the most common sites of involvement were the head and neck (69%), extremities (61%), and trunk (44%). About half of the cohort (51%) had mild disease, 15% had culture-confirmed infections (9% had Streptococcal infections), and 66% of patients reported itch as a symptom.

The researchers observed that inverse psoriasis was significantly more common in infants and decreased with age. Anogenital involvement was more common in males and in those aged 0-2, while head and neck involvement was more common in females. Nail involvement was more common in childhood.

Topical therapy was the most common treatment overall and by far the most common among those in the 0-2 age category. “Overall, phototherapy was used in childhood and adolescents but almost never in infancy,” Ms. Aghdasi said. “Looking at changes in systemic treatment over time, conventional systemic use increased in infants and children and decreased in adolescents. Biologic use increased in all ages, most notably in children aged 3-12 years old.”

Multivariate regression analyses revealed that the following independent variables predicted moderate to severe psoriasis: adolescent age (adjusted odds ratio, 1.9; P = .03), guttate morphology (aOR, 2.2; P = .006), plaque and guttate morphology (aOR, 7.6; P less than .001), pustular or erythrodermic morphology (aOR, 5; P = .003), culture-confirmed infection (aOR, 2; P = .007), Black race (aOR, 3.3; P = .007), Asian race (aOR, 1.8; P = .04, and Hispanic race (aOR, 1.9; P = .03).

“Further analysis is needed to elucidate the influence of race on severity and of the clinical utility of infection as a marker of severity,” Ms. Aghdasi said. “Interestingly, we did not find that obesity was a marker of severity in our cohort.”

In an interview, senior study author Kelly M. Cordoro, MD, professor of dermatology and pediatrics at UCSF, noted that this finding conflicts with prior studies showing an association between obesity and severe psoriasis in children.

[email protected]

Psoriasis affects over 7.5 million adults in the United States, with prevalence nearly twice as high among Whites as non-Whites, according to an analysis of national survey data from 2011 to 2014.

“The adult prevalence rate of 3.0% continues to place psoriasis as one of the most common immune-mediated diseases affecting adults” in the United States, April W. Armstrong, MD, MPH, and associates said in a report published in JAMA Dermatology. At that rate, approximately 7,560,000 Americans aged 20 years or older have psoriasis.

That overall rate among adults aged 20 years and older, based on data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES), did not change significantly when compared with the 2003-2004 NHANES, when it was 3.15% among those aged 20-59, said Dr. Armstrong, professor of dermatology, University of Southern California, Los Angeles, and associates.

For the 2011-2014 period, psoriasis prevalence was similar between women (3.2%) and men (2.8%) but was significantly associated with older age and White/non-White status. Those aged 50-59 years had the highest prevalence of any age group at 4.3% and those aged 70 and older had a rate of 3.9%, while those aged 20-29 were the lowest at 1.6%, the investigators reported.

The prevalence in non-Hispanic Whites in the United States was 3.6% over the study period, and their odds ratio for having psoriasis was 1.92, compared with non-White individuals. Asian respondents had a prevalence of 2.5%, with the Hispanic population at 1.9%, non-Hispanic Black respondents at 1.5%, and those identifying as other (including multiracial persons) at 3.1%, they said.

The NHANES sample consisted of 12,638 people who had participated in the question that asked if they had ever been diagnosed with psoriasis by a physician or other health care professional, of whom 12,625 gave a definitive yes or no answer, the investigators noted.

A much smaller number, 329, also answered a question about the severity of their disease: Fifty-six percent had little or no psoriasis, almost 22% reported 1-2 palms of involvement, 16% had 3-10 palms of involvement, and 5.5% said the coverage was more than 10 palms. Since the survey did not distinguish between treated and untreated patients, however, some “of those reporting low body surface area involvement may be receiving treatments that are controlling their otherwise more extensive disease,” they wrote.

Dr. Armstrong and another investigator said that they have received grants, personal fees, and honoraria from a number of pharmaceutical companies; two other investigators are employees of the National Psoriasis Foundation.

[email protected]

Psoriasis affects over 7.5 million adults in the United States, with prevalence nearly twice as high among Whites as non-Whites, according to an analysis of national survey data from 2011 to 2014.

“The adult prevalence rate of 3.0% continues to place psoriasis as one of the most common immune-mediated diseases affecting adults” in the United States, April W. Armstrong, MD, MPH, and associates said in a report published in JAMA Dermatology. At that rate, approximately 7,560,000 Americans aged 20 years or older have psoriasis.

That overall rate among adults aged 20 years and older, based on data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES), did not change significantly when compared with the 2003-2004 NHANES, when it was 3.15% among those aged 20-59, said Dr. Armstrong, professor of dermatology, University of Southern California, Los Angeles, and associates.

For the 2011-2014 period, psoriasis prevalence was similar between women (3.2%) and men (2.8%) but was significantly associated with older age and White/non-White status. Those aged 50-59 years had the highest prevalence of any age group at 4.3% and those aged 70 and older had a rate of 3.9%, while those aged 20-29 were the lowest at 1.6%, the investigators reported.

The prevalence in non-Hispanic Whites in the United States was 3.6% over the study period, and their odds ratio for having psoriasis was 1.92, compared with non-White individuals. Asian respondents had a prevalence of 2.5%, with the Hispanic population at 1.9%, non-Hispanic Black respondents at 1.5%, and those identifying as other (including multiracial persons) at 3.1%, they said.

The NHANES sample consisted of 12,638 people who had participated in the question that asked if they had ever been diagnosed with psoriasis by a physician or other health care professional, of whom 12,625 gave a definitive yes or no answer, the investigators noted.

A much smaller number, 329, also answered a question about the severity of their disease: Fifty-six percent had little or no psoriasis, almost 22% reported 1-2 palms of involvement, 16% had 3-10 palms of involvement, and 5.5% said the coverage was more than 10 palms. Since the survey did not distinguish between treated and untreated patients, however, some “of those reporting low body surface area involvement may be receiving treatments that are controlling their otherwise more extensive disease,” they wrote.

Dr. Armstrong and another investigator said that they have received grants, personal fees, and honoraria from a number of pharmaceutical companies; two other investigators are employees of the National Psoriasis Foundation.

[email protected]

Psoriasis affects over 7.5 million adults in the United States, with prevalence nearly twice as high among Whites as non-Whites, according to an analysis of national survey data from 2011 to 2014.

“The adult prevalence rate of 3.0% continues to place psoriasis as one of the most common immune-mediated diseases affecting adults” in the United States, April W. Armstrong, MD, MPH, and associates said in a report published in JAMA Dermatology. At that rate, approximately 7,560,000 Americans aged 20 years or older have psoriasis.

That overall rate among adults aged 20 years and older, based on data from the 2011-2012 and 2013-2014 cycles of the National Health and Nutrition Examination Survey (NHANES), did not change significantly when compared with the 2003-2004 NHANES, when it was 3.15% among those aged 20-59, said Dr. Armstrong, professor of dermatology, University of Southern California, Los Angeles, and associates.

For the 2011-2014 period, psoriasis prevalence was similar between women (3.2%) and men (2.8%) but was significantly associated with older age and White/non-White status. Those aged 50-59 years had the highest prevalence of any age group at 4.3% and those aged 70 and older had a rate of 3.9%, while those aged 20-29 were the lowest at 1.6%, the investigators reported.

The prevalence in non-Hispanic Whites in the United States was 3.6% over the study period, and their odds ratio for having psoriasis was 1.92, compared with non-White individuals. Asian respondents had a prevalence of 2.5%, with the Hispanic population at 1.9%, non-Hispanic Black respondents at 1.5%, and those identifying as other (including multiracial persons) at 3.1%, they said.

The NHANES sample consisted of 12,638 people who had participated in the question that asked if they had ever been diagnosed with psoriasis by a physician or other health care professional, of whom 12,625 gave a definitive yes or no answer, the investigators noted.

A much smaller number, 329, also answered a question about the severity of their disease: Fifty-six percent had little or no psoriasis, almost 22% reported 1-2 palms of involvement, 16% had 3-10 palms of involvement, and 5.5% said the coverage was more than 10 palms. Since the survey did not distinguish between treated and untreated patients, however, some “of those reporting low body surface area involvement may be receiving treatments that are controlling their otherwise more extensive disease,” they wrote.

Dr. Armstrong and another investigator said that they have received grants, personal fees, and honoraria from a number of pharmaceutical companies; two other investigators are employees of the National Psoriasis Foundation.

[email protected]

Malignancy rates were low in patients with psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis who were treated with secukinumab, for up to 5 years, based on data from a safety analysis that included 49 clinical trials.

Secukinumab (Cosentyx), an interleukin-17A antagonist, is approved for several conditions: moderate to severe psoriasis in children and adults, PsA, ankylosing spondylitis (AS), and nonradiographic axial spondyloarthritis.

Although secukinumab has demonstrated safety and tolerability, data on long-term malignancy rates are limited, wrote Mark Lebwohl, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors.

In a study published in the British Journal of Dermatology, they analyzed the combined safety data from clinical trials and postmarketing surveillance. The study population included 10,685 patients with psoriasis, 2,523 patients with PsA, and 1,311 patients with ankylosing spondylitis who received at least one approved dose of secukinumab (300 mg or 150 mg). The maximum follow-up was 5 years. The exposure-adjusted incidence rate was defined as the incidence rates per 100 patient treatment-years (PTY). The cumulative exposure for patients with psoriasis, PsA, and AS was 16,482, 4,944, and 2,668 PTY, respectively, with average follow-up times of 1.54, 1.96, and 2.03 years, respectively.

The observed and the expected number of malignancies were comparable, with a standardized incidence ratio (SIR) for malignancy of 0.99 across all treatment indications, the researchers said. In further analysis of malignancy by indication, the SIR was 0.87, 1.16, and 1.61 for psoriasis, PsA, and AS, respectively.

Data from postmarketing surveillance showed similar results: The estimated crude cumulative incidence reporting rate per 100 PTY was 0.27 for malignancy across all indications. The cumulative exposure was 285,811 PTY.

The study findings were limited by several factors including the post hoc design, differences in clinical trial methodologies, and lack of controlling for confounding variables, such as smoking status and previous exposure to systemic and biologic treatments, the researchers noted. In addition, the analysis did not include postexposure follow-up data, or data on patients who discontinued clinical trials, they said.

Overall, the analysis is the largest to date and supports the low risk of malignancy in patients with psoriasis, PsA, and AS treated with secukinumab, the researchers noted.

However, “while this assessment provides a broader understanding of the safety of secukinumab and supports its long-term use in these chronic systemic inflammatory conditions, registry data are further warranted to fully understand the real-world effect of biologics on malignancy risk,” they concluded.

“Secukinumab is a relatively newer biologic, approved in 2015, and there is currently a lack of longer-term data on the incidence of malignancy in secukinumab-treated patients, so it’s important to look at the data we have so far on this topic so we can better understand the long-term risks and counsel our psoriasis and psoriatic arthritis patients,” Flavia Fedeles, MD, of the department of dermatology at Massachusetts General Hospital, Boston, said in an interview.

Dr. Fedeles, who was not involved with the study, said that she was not surprised by the study results. “Data reported in the past from phase 3 clinical trials of secukinumab compared with placebo did not show an increase in risk of malignancy, though at that time no long-term safety data or data from patients with history of malignancy was available,” she said. “This study is reassuring in that there wasn’t a signal of increased malignancy events up to 5 years of secukinumab treatment,” said Dr. Fedeles.

Malignancy rates were low in patients with psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis who were treated with secukinumab, for up to 5 years, based on data from a safety analysis that included 49 clinical trials.

Secukinumab (Cosentyx), an interleukin-17A antagonist, is approved for several conditions: moderate to severe psoriasis in children and adults, PsA, ankylosing spondylitis (AS), and nonradiographic axial spondyloarthritis.

Although secukinumab has demonstrated safety and tolerability, data on long-term malignancy rates are limited, wrote Mark Lebwohl, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors.

In a study published in the British Journal of Dermatology, they analyzed the combined safety data from clinical trials and postmarketing surveillance. The study population included 10,685 patients with psoriasis, 2,523 patients with PsA, and 1,311 patients with ankylosing spondylitis who received at least one approved dose of secukinumab (300 mg or 150 mg). The maximum follow-up was 5 years. The exposure-adjusted incidence rate was defined as the incidence rates per 100 patient treatment-years (PTY). The cumulative exposure for patients with psoriasis, PsA, and AS was 16,482, 4,944, and 2,668 PTY, respectively, with average follow-up times of 1.54, 1.96, and 2.03 years, respectively.

The observed and the expected number of malignancies were comparable, with a standardized incidence ratio (SIR) for malignancy of 0.99 across all treatment indications, the researchers said. In further analysis of malignancy by indication, the SIR was 0.87, 1.16, and 1.61 for psoriasis, PsA, and AS, respectively.

Data from postmarketing surveillance showed similar results: The estimated crude cumulative incidence reporting rate per 100 PTY was 0.27 for malignancy across all indications. The cumulative exposure was 285,811 PTY.

The study findings were limited by several factors including the post hoc design, differences in clinical trial methodologies, and lack of controlling for confounding variables, such as smoking status and previous exposure to systemic and biologic treatments, the researchers noted. In addition, the analysis did not include postexposure follow-up data, or data on patients who discontinued clinical trials, they said.

Overall, the analysis is the largest to date and supports the low risk of malignancy in patients with psoriasis, PsA, and AS treated with secukinumab, the researchers noted.

However, “while this assessment provides a broader understanding of the safety of secukinumab and supports its long-term use in these chronic systemic inflammatory conditions, registry data are further warranted to fully understand the real-world effect of biologics on malignancy risk,” they concluded.

“Secukinumab is a relatively newer biologic, approved in 2015, and there is currently a lack of longer-term data on the incidence of malignancy in secukinumab-treated patients, so it’s important to look at the data we have so far on this topic so we can better understand the long-term risks and counsel our psoriasis and psoriatic arthritis patients,” Flavia Fedeles, MD, of the department of dermatology at Massachusetts General Hospital, Boston, said in an interview.

Dr. Fedeles, who was not involved with the study, said that she was not surprised by the study results. “Data reported in the past from phase 3 clinical trials of secukinumab compared with placebo did not show an increase in risk of malignancy, though at that time no long-term safety data or data from patients with history of malignancy was available,” she said. “This study is reassuring in that there wasn’t a signal of increased malignancy events up to 5 years of secukinumab treatment,” said Dr. Fedeles.

Malignancy rates were low in patients with psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis who were treated with secukinumab, for up to 5 years, based on data from a safety analysis that included 49 clinical trials.

Secukinumab (Cosentyx), an interleukin-17A antagonist, is approved for several conditions: moderate to severe psoriasis in children and adults, PsA, ankylosing spondylitis (AS), and nonradiographic axial spondyloarthritis.

Although secukinumab has demonstrated safety and tolerability, data on long-term malignancy rates are limited, wrote Mark Lebwohl, MD, professor of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors.

In a study published in the British Journal of Dermatology, they analyzed the combined safety data from clinical trials and postmarketing surveillance. The study population included 10,685 patients with psoriasis, 2,523 patients with PsA, and 1,311 patients with ankylosing spondylitis who received at least one approved dose of secukinumab (300 mg or 150 mg). The maximum follow-up was 5 years. The exposure-adjusted incidence rate was defined as the incidence rates per 100 patient treatment-years (PTY). The cumulative exposure for patients with psoriasis, PsA, and AS was 16,482, 4,944, and 2,668 PTY, respectively, with average follow-up times of 1.54, 1.96, and 2.03 years, respectively.

The observed and the expected number of malignancies were comparable, with a standardized incidence ratio (SIR) for malignancy of 0.99 across all treatment indications, the researchers said. In further analysis of malignancy by indication, the SIR was 0.87, 1.16, and 1.61 for psoriasis, PsA, and AS, respectively.

Data from postmarketing surveillance showed similar results: The estimated crude cumulative incidence reporting rate per 100 PTY was 0.27 for malignancy across all indications. The cumulative exposure was 285,811 PTY.

The study findings were limited by several factors including the post hoc design, differences in clinical trial methodologies, and lack of controlling for confounding variables, such as smoking status and previous exposure to systemic and biologic treatments, the researchers noted. In addition, the analysis did not include postexposure follow-up data, or data on patients who discontinued clinical trials, they said.

Overall, the analysis is the largest to date and supports the low risk of malignancy in patients with psoriasis, PsA, and AS treated with secukinumab, the researchers noted.

However, “while this assessment provides a broader understanding of the safety of secukinumab and supports its long-term use in these chronic systemic inflammatory conditions, registry data are further warranted to fully understand the real-world effect of biologics on malignancy risk,” they concluded.

“Secukinumab is a relatively newer biologic, approved in 2015, and there is currently a lack of longer-term data on the incidence of malignancy in secukinumab-treated patients, so it’s important to look at the data we have so far on this topic so we can better understand the long-term risks and counsel our psoriasis and psoriatic arthritis patients,” Flavia Fedeles, MD, of the department of dermatology at Massachusetts General Hospital, Boston, said in an interview.

Dr. Fedeles, who was not involved with the study, said that she was not surprised by the study results. “Data reported in the past from phase 3 clinical trials of secukinumab compared with placebo did not show an increase in risk of malignancy, though at that time no long-term safety data or data from patients with history of malignancy was available,” she said. “This study is reassuring in that there wasn’t a signal of increased malignancy events up to 5 years of secukinumab treatment,” said Dr. Fedeles.

Psoriasis patients treated with biological disease-modifying antirheumatic drugs had a significantly lower incidence of psoriatic arthritis (PsA) compared with those treated with phototherapy, in a study of 464 adults.

Epidemiologic data show that PsA may be diagnosed as long as 5-10 years after a diagnosis of plaque psoriasis, but PsA ultimately occurs in up to 25% of cases, wrote the study investigators, Paolo Gisondi, MD, of the section of dermatology and venereology, department of medicine, at Università degli Studi di Verona, Italy, and colleagues.

“The delay between the onset of skin manifestations of psoriasis and joint disease may provide a therapeutic window of clinical opportunity for preventing the progression from psoriasis to PsA,” but the impact of continuous systemic treatment with biological disease-modifying antirheumatic drugs (DMARDs) has not been well studied, the researchers said.

In the retrospective, nonrandomized study published in Annals of the Rheumatic Diseases, the researchers reviewed data from adults with moderate to severe plaque psoriasis who received continuous treatment with biologic DMARDs, compared with those who received narrow-band ultraviolet light B (nb-UVB) phototherapy, between January 2012 and September 2020.

Patients with a past or present PsA diagnosis were excluded from the study. A total of 234 patients were treated with biologic DMARDs for at least 5 years and 230 were treated with at least three courses of nb-UVB phototherapy; all patients were followed for an average of 7 years.

PsA was determined based on the Classification for Psoriatic Arthritis criteria. Incidence was defined in terms of cases per 100 patients per year.

During the follow-up period, 51 patients (11%) developed incident PsA: 19 (8%) in the biologic DMARDs group and 32 (14%) in the nb-UVB phototherapy group. The annual incidence rate of PsA was 1.20 cases per 100 patients per year in the biologic DMARDs group compared with 2.17 cases per 100 patients per year in the phototherapy group (P = .006).

In a multivariate analysis, independent risk factors for PsA were older age (adjusted hazard ratio, 1.04; P < .001), nail psoriasis (aHR 3.15; P = .001), and psoriasis duration greater than 10 years (aHR, 2.02; P = .001). Most other baseline demographics, including smoking status, baseline Psoriasis Area and Severity Index (PASI) scores, and comorbidities, were similar in patients who did and did not develop PsA.

Of the patients taking biologic DMARDs, 39 (17%) were treated with infliximab, 17 (7%) with etanercept, 67 (29%) with adalimumab, 50 (21%) with ustekinumab, and 61 (26%) with secukinumab; 35 of these patients switched biologics during the study period.

The study findings were limited by several factors including the retrospective design and the resulting potential for biases, notably the potential confounding bias by indication because of the lack of randomization, the researchers noted. Another limitation was the inability to perform a subgroup analysis of biologic DMARD classes because of the small sample size, the authors said. However, they added, the findings were strengthened by the complete database and accurate PsA diagnoses supported by an expert rheumatologist.

Larger prospective and intervention studies are needed to validate the results, the researchers emphasized. However, data from the current study suggest that continued treatment with biologic DMARDs “may reduce the risk of incident PsA in patients with moderate to severe chronic plaque psoriasis,” they concluded.

The study was supported by the European Union’s Horizon 2020 Research and Innovation Program. Dr. Gisondi and several coauthors disclosed relationships with Abbvie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi, and UCB. The study was supported by the European Union’s Horizon 2020 Research and Innovation Program.

Psoriasis patients treated with biological disease-modifying antirheumatic drugs had a significantly lower incidence of psoriatic arthritis (PsA) compared with those treated with phototherapy, in a study of 464 adults.

Epidemiologic data show that PsA may be diagnosed as long as 5-10 years after a diagnosis of plaque psoriasis, but PsA ultimately occurs in up to 25% of cases, wrote the study investigators, Paolo Gisondi, MD, of the section of dermatology and venereology, department of medicine, at Università degli Studi di Verona, Italy, and colleagues.

“The delay between the onset of skin manifestations of psoriasis and joint disease may provide a therapeutic window of clinical opportunity for preventing the progression from psoriasis to PsA,” but the impact of continuous systemic treatment with biological disease-modifying antirheumatic drugs (DMARDs) has not been well studied, the researchers said.

In the retrospective, nonrandomized study published in Annals of the Rheumatic Diseases, the researchers reviewed data from adults with moderate to severe plaque psoriasis who received continuous treatment with biologic DMARDs, compared with those who received narrow-band ultraviolet light B (nb-UVB) phototherapy, between January 2012 and September 2020.

Patients with a past or present PsA diagnosis were excluded from the study. A total of 234 patients were treated with biologic DMARDs for at least 5 years and 230 were treated with at least three courses of nb-UVB phototherapy; all patients were followed for an average of 7 years.

PsA was determined based on the Classification for Psoriatic Arthritis criteria. Incidence was defined in terms of cases per 100 patients per year.

During the follow-up period, 51 patients (11%) developed incident PsA: 19 (8%) in the biologic DMARDs group and 32 (14%) in the nb-UVB phototherapy group. The annual incidence rate of PsA was 1.20 cases per 100 patients per year in the biologic DMARDs group compared with 2.17 cases per 100 patients per year in the phototherapy group (P = .006).

In a multivariate analysis, independent risk factors for PsA were older age (adjusted hazard ratio, 1.04; P < .001), nail psoriasis (aHR 3.15; P = .001), and psoriasis duration greater than 10 years (aHR, 2.02; P = .001). Most other baseline demographics, including smoking status, baseline Psoriasis Area and Severity Index (PASI) scores, and comorbidities, were similar in patients who did and did not develop PsA.

Of the patients taking biologic DMARDs, 39 (17%) were treated with infliximab, 17 (7%) with etanercept, 67 (29%) with adalimumab, 50 (21%) with ustekinumab, and 61 (26%) with secukinumab; 35 of these patients switched biologics during the study period.

The study findings were limited by several factors including the retrospective design and the resulting potential for biases, notably the potential confounding bias by indication because of the lack of randomization, the researchers noted. Another limitation was the inability to perform a subgroup analysis of biologic DMARD classes because of the small sample size, the authors said. However, they added, the findings were strengthened by the complete database and accurate PsA diagnoses supported by an expert rheumatologist.

Larger prospective and intervention studies are needed to validate the results, the researchers emphasized. However, data from the current study suggest that continued treatment with biologic DMARDs “may reduce the risk of incident PsA in patients with moderate to severe chronic plaque psoriasis,” they concluded.

The study was supported by the European Union’s Horizon 2020 Research and Innovation Program. Dr. Gisondi and several coauthors disclosed relationships with Abbvie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi, and UCB. The study was supported by the European Union’s Horizon 2020 Research and Innovation Program.

Psoriasis patients treated with biological disease-modifying antirheumatic drugs had a significantly lower incidence of psoriatic arthritis (PsA) compared with those treated with phototherapy, in a study of 464 adults.

Epidemiologic data show that PsA may be diagnosed as long as 5-10 years after a diagnosis of plaque psoriasis, but PsA ultimately occurs in up to 25% of cases, wrote the study investigators, Paolo Gisondi, MD, of the section of dermatology and venereology, department of medicine, at Università degli Studi di Verona, Italy, and colleagues.

“The delay between the onset of skin manifestations of psoriasis and joint disease may provide a therapeutic window of clinical opportunity for preventing the progression from psoriasis to PsA,” but the impact of continuous systemic treatment with biological disease-modifying antirheumatic drugs (DMARDs) has not been well studied, the researchers said.

In the retrospective, nonrandomized study published in Annals of the Rheumatic Diseases, the researchers reviewed data from adults with moderate to severe plaque psoriasis who received continuous treatment with biologic DMARDs, compared with those who received narrow-band ultraviolet light B (nb-UVB) phototherapy, between January 2012 and September 2020.

Patients with a past or present PsA diagnosis were excluded from the study. A total of 234 patients were treated with biologic DMARDs for at least 5 years and 230 were treated with at least three courses of nb-UVB phototherapy; all patients were followed for an average of 7 years.

PsA was determined based on the Classification for Psoriatic Arthritis criteria. Incidence was defined in terms of cases per 100 patients per year.

During the follow-up period, 51 patients (11%) developed incident PsA: 19 (8%) in the biologic DMARDs group and 32 (14%) in the nb-UVB phototherapy group. The annual incidence rate of PsA was 1.20 cases per 100 patients per year in the biologic DMARDs group compared with 2.17 cases per 100 patients per year in the phototherapy group (P = .006).

In a multivariate analysis, independent risk factors for PsA were older age (adjusted hazard ratio, 1.04; P < .001), nail psoriasis (aHR 3.15; P = .001), and psoriasis duration greater than 10 years (aHR, 2.02; P = .001). Most other baseline demographics, including smoking status, baseline Psoriasis Area and Severity Index (PASI) scores, and comorbidities, were similar in patients who did and did not develop PsA.

Of the patients taking biologic DMARDs, 39 (17%) were treated with infliximab, 17 (7%) with etanercept, 67 (29%) with adalimumab, 50 (21%) with ustekinumab, and 61 (26%) with secukinumab; 35 of these patients switched biologics during the study period.

The study findings were limited by several factors including the retrospective design and the resulting potential for biases, notably the potential confounding bias by indication because of the lack of randomization, the researchers noted. Another limitation was the inability to perform a subgroup analysis of biologic DMARD classes because of the small sample size, the authors said. However, they added, the findings were strengthened by the complete database and accurate PsA diagnoses supported by an expert rheumatologist.

Larger prospective and intervention studies are needed to validate the results, the researchers emphasized. However, data from the current study suggest that continued treatment with biologic DMARDs “may reduce the risk of incident PsA in patients with moderate to severe chronic plaque psoriasis,” they concluded.

The study was supported by the European Union’s Horizon 2020 Research and Innovation Program. Dr. Gisondi and several coauthors disclosed relationships with Abbvie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Novartis, Pierre Fabre, Sandoz, Sanofi, and UCB. The study was supported by the European Union’s Horizon 2020 Research and Innovation Program.