Psoriasis

Key clinical point: Anxiety and depressive symptoms, individually or in concurrence, were prevalent among patients with plaque psoriasis. Depressive symptoms seemed to have more impact on psoriasis and patient health-related quality of life (QoL) than anxiety symptoms.

Major finding: Overall, 27% and 22% of patients had symptoms of anxiety and depression, respectively, whereas 14% of patients had both. Patients with vs. without depression had significantly higher itch (6.0 vs 3.0; P = .009) and skin pain (2.5 vs 1.0; P = .01) numeric rating scale (NRS) score. However, itch (P = .42) and skin pain (P = .06) NRS were not significantly different in patients with vs. without anxiety.

Study details: Findings are from an analysis of 73 Japanese patients aged 18 years or more with plaque psoriasis without peripheral arthritis symptoms from the ProLOGUE study.

Disclosures: The study was sponsored by Kyowa Kirin Co., Ltd. Dr. Ohata, Dr. Murotani, and Dr. Imafuku declared receiving grants, personal fees, meeting and travel expenses, or nonfinancial support from various sources, including Kyowa Kirin Co., Ltd. Dr. Kanai and Mr. Kitabayashi reported being employees of Kyowa Kirin Co. Ltd.

Source: Ohata C et al. J Eur Acad Dermatol Venereol. 2021 Aug 21. doi: 10.1111/jdv.17621.

Key clinical point: Anxiety and depressive symptoms, individually or in concurrence, were prevalent among patients with plaque psoriasis. Depressive symptoms seemed to have more impact on psoriasis and patient health-related quality of life (QoL) than anxiety symptoms.

Major finding: Overall, 27% and 22% of patients had symptoms of anxiety and depression, respectively, whereas 14% of patients had both. Patients with vs. without depression had significantly higher itch (6.0 vs 3.0; P = .009) and skin pain (2.5 vs 1.0; P = .01) numeric rating scale (NRS) score. However, itch (P = .42) and skin pain (P = .06) NRS were not significantly different in patients with vs. without anxiety.

Study details: Findings are from an analysis of 73 Japanese patients aged 18 years or more with plaque psoriasis without peripheral arthritis symptoms from the ProLOGUE study.

Disclosures: The study was sponsored by Kyowa Kirin Co., Ltd. Dr. Ohata, Dr. Murotani, and Dr. Imafuku declared receiving grants, personal fees, meeting and travel expenses, or nonfinancial support from various sources, including Kyowa Kirin Co., Ltd. Dr. Kanai and Mr. Kitabayashi reported being employees of Kyowa Kirin Co. Ltd.

Source: Ohata C et al. J Eur Acad Dermatol Venereol. 2021 Aug 21. doi: 10.1111/jdv.17621.

Key clinical point: Anxiety and depressive symptoms, individually or in concurrence, were prevalent among patients with plaque psoriasis. Depressive symptoms seemed to have more impact on psoriasis and patient health-related quality of life (QoL) than anxiety symptoms.

Major finding: Overall, 27% and 22% of patients had symptoms of anxiety and depression, respectively, whereas 14% of patients had both. Patients with vs. without depression had significantly higher itch (6.0 vs 3.0; P = .009) and skin pain (2.5 vs 1.0; P = .01) numeric rating scale (NRS) score. However, itch (P = .42) and skin pain (P = .06) NRS were not significantly different in patients with vs. without anxiety.

Study details: Findings are from an analysis of 73 Japanese patients aged 18 years or more with plaque psoriasis without peripheral arthritis symptoms from the ProLOGUE study.

Disclosures: The study was sponsored by Kyowa Kirin Co., Ltd. Dr. Ohata, Dr. Murotani, and Dr. Imafuku declared receiving grants, personal fees, meeting and travel expenses, or nonfinancial support from various sources, including Kyowa Kirin Co., Ltd. Dr. Kanai and Mr. Kitabayashi reported being employees of Kyowa Kirin Co. Ltd.

Source: Ohata C et al. J Eur Acad Dermatol Venereol. 2021 Aug 21. doi: 10.1111/jdv.17621.

High out-of-pocket costs for medications remain a barrier for patients with psoriasis or psoriatic arthritis on Medicare, according to findings from a cross-sectional analysis of the Centers for Medicare & Medicaid Services Prescription Drug Plan Formulary Data from the fourth quarter of 2020.

Mathier/Thinkstock

Although biologics have demonstrated safety and effectiveness for psoriasis and psoriatic arthritis, their costs have risen, which has led patients to switch or discontinue biologics and consequently incur greater health care costs, wrote Sarah P. Pourali and colleagues at Vanderbilt University, Nashville, Tenn.

The authors also noted that Medicare patients in particular experience a financial burden if they have no limits on out-of-pocket spending, and while patient assistance programs may offset some out-of-pocket spending for specialty drugs, not all patients are aware of or qualify for them. Ineligibility for low-income subsidies also serves as a barrier and is associated with lower adherence to treatment.

In a study published in JAMA Dermatology, the researchers identified 5,011 formularies using the CMS data. The medications were etanercept, adalimumab, golimumab, ustekinumab, certolizumab pegol, apremilast, secukinumab, abatacept, ixekizumab, brodalumab, tofacitinib, tofacitinib XR, guselkumab, tildrakizumab, and risankizumab.

Overall, coverage for those 15 specialty medications ranged from 10.0% to 99.8% across products and Part D plans. The most commonly covered medications were adalimumab and ustekinumab (99.8% for both) and the least covered were brodalumab and tildrakizumab (10.9% and 10.0%, respectively).

Prior authorization was required by 90.5%-100% of the plans when medications were covered, and plans with limits on the quantity of medications covered ranged from 1.0% of plans (for guselkumab) to 78% of plans (for tofacitinib).

Copays were relatively rare; 2.4%-5.5% of the plans offered copays on any of the 15 medications.

The standard Medicare benefit for 2021 included a $445 deductible, 25% coinsurance for initial drug spending, and 5% coinsurance for drug spending in the catastrophic phase of coverage, the researchers noted. Overall, apremilast had the lowest estimated out-of-pocket costs for initial fills, under the catastrophic coverage phase, and annual cost, and ustekinumab had the highest. The estimated out-of-pocket costs for an initial fill ranged from $1,234 for apremilast to $3,426 for ustekinumab. Out-of-pocket costs for medications under the catastrophic phase ranged from $181 for apremilast to $1,175 for ustekinumab. Estimated out-of-pocket costs for a year of treatment ranged from $4,423 for apremilast to $6,950 for ustekinumab.

Median point-of-sale prices per fill – meaning pricing with no rebates or discounts – were lowest for apremilast ($3,620.40) and reached $23,492.93 per fill for ustekinumab, the researchers wrote. Other medications with point-of-sale prices above $10,000 were guselkumab ($11,511.52), tildrakizumab ($14,112.13), and risankizumab ($16,248.90).

The study was supported by grants from the Commonwealth Fund and the Leukemia & Lymphoma Society. One author disclosed receiving grants from Arnold Ventures, the Commonwealth Fund, and the Robert Wood Johnson Foundation for unrelated work, as well as honoraria from West Health and the Institute for Clinical and Economic Review.

High out-of-pocket costs for medications remain a barrier for patients with psoriasis or psoriatic arthritis on Medicare, according to findings from a cross-sectional analysis of the Centers for Medicare & Medicaid Services Prescription Drug Plan Formulary Data from the fourth quarter of 2020.

Mathier/Thinkstock

Although biologics have demonstrated safety and effectiveness for psoriasis and psoriatic arthritis, their costs have risen, which has led patients to switch or discontinue biologics and consequently incur greater health care costs, wrote Sarah P. Pourali and colleagues at Vanderbilt University, Nashville, Tenn.

The authors also noted that Medicare patients in particular experience a financial burden if they have no limits on out-of-pocket spending, and while patient assistance programs may offset some out-of-pocket spending for specialty drugs, not all patients are aware of or qualify for them. Ineligibility for low-income subsidies also serves as a barrier and is associated with lower adherence to treatment.

In a study published in JAMA Dermatology, the researchers identified 5,011 formularies using the CMS data. The medications were etanercept, adalimumab, golimumab, ustekinumab, certolizumab pegol, apremilast, secukinumab, abatacept, ixekizumab, brodalumab, tofacitinib, tofacitinib XR, guselkumab, tildrakizumab, and risankizumab.

Overall, coverage for those 15 specialty medications ranged from 10.0% to 99.8% across products and Part D plans. The most commonly covered medications were adalimumab and ustekinumab (99.8% for both) and the least covered were brodalumab and tildrakizumab (10.9% and 10.0%, respectively).

Prior authorization was required by 90.5%-100% of the plans when medications were covered, and plans with limits on the quantity of medications covered ranged from 1.0% of plans (for guselkumab) to 78% of plans (for tofacitinib).

Copays were relatively rare; 2.4%-5.5% of the plans offered copays on any of the 15 medications.

The standard Medicare benefit for 2021 included a $445 deductible, 25% coinsurance for initial drug spending, and 5% coinsurance for drug spending in the catastrophic phase of coverage, the researchers noted. Overall, apremilast had the lowest estimated out-of-pocket costs for initial fills, under the catastrophic coverage phase, and annual cost, and ustekinumab had the highest. The estimated out-of-pocket costs for an initial fill ranged from $1,234 for apremilast to $3,426 for ustekinumab. Out-of-pocket costs for medications under the catastrophic phase ranged from $181 for apremilast to $1,175 for ustekinumab. Estimated out-of-pocket costs for a year of treatment ranged from $4,423 for apremilast to $6,950 for ustekinumab.

Median point-of-sale prices per fill – meaning pricing with no rebates or discounts – were lowest for apremilast ($3,620.40) and reached $23,492.93 per fill for ustekinumab, the researchers wrote. Other medications with point-of-sale prices above $10,000 were guselkumab ($11,511.52), tildrakizumab ($14,112.13), and risankizumab ($16,248.90).

The study was supported by grants from the Commonwealth Fund and the Leukemia & Lymphoma Society. One author disclosed receiving grants from Arnold Ventures, the Commonwealth Fund, and the Robert Wood Johnson Foundation for unrelated work, as well as honoraria from West Health and the Institute for Clinical and Economic Review.

High out-of-pocket costs for medications remain a barrier for patients with psoriasis or psoriatic arthritis on Medicare, according to findings from a cross-sectional analysis of the Centers for Medicare & Medicaid Services Prescription Drug Plan Formulary Data from the fourth quarter of 2020.

Mathier/Thinkstock

Although biologics have demonstrated safety and effectiveness for psoriasis and psoriatic arthritis, their costs have risen, which has led patients to switch or discontinue biologics and consequently incur greater health care costs, wrote Sarah P. Pourali and colleagues at Vanderbilt University, Nashville, Tenn.

The authors also noted that Medicare patients in particular experience a financial burden if they have no limits on out-of-pocket spending, and while patient assistance programs may offset some out-of-pocket spending for specialty drugs, not all patients are aware of or qualify for them. Ineligibility for low-income subsidies also serves as a barrier and is associated with lower adherence to treatment.

In a study published in JAMA Dermatology, the researchers identified 5,011 formularies using the CMS data. The medications were etanercept, adalimumab, golimumab, ustekinumab, certolizumab pegol, apremilast, secukinumab, abatacept, ixekizumab, brodalumab, tofacitinib, tofacitinib XR, guselkumab, tildrakizumab, and risankizumab.

Overall, coverage for those 15 specialty medications ranged from 10.0% to 99.8% across products and Part D plans. The most commonly covered medications were adalimumab and ustekinumab (99.8% for both) and the least covered were brodalumab and tildrakizumab (10.9% and 10.0%, respectively).

Prior authorization was required by 90.5%-100% of the plans when medications were covered, and plans with limits on the quantity of medications covered ranged from 1.0% of plans (for guselkumab) to 78% of plans (for tofacitinib).

Copays were relatively rare; 2.4%-5.5% of the plans offered copays on any of the 15 medications.

The standard Medicare benefit for 2021 included a $445 deductible, 25% coinsurance for initial drug spending, and 5% coinsurance for drug spending in the catastrophic phase of coverage, the researchers noted. Overall, apremilast had the lowest estimated out-of-pocket costs for initial fills, under the catastrophic coverage phase, and annual cost, and ustekinumab had the highest. The estimated out-of-pocket costs for an initial fill ranged from $1,234 for apremilast to $3,426 for ustekinumab. Out-of-pocket costs for medications under the catastrophic phase ranged from $181 for apremilast to $1,175 for ustekinumab. Estimated out-of-pocket costs for a year of treatment ranged from $4,423 for apremilast to $6,950 for ustekinumab.

Median point-of-sale prices per fill – meaning pricing with no rebates or discounts – were lowest for apremilast ($3,620.40) and reached $23,492.93 per fill for ustekinumab, the researchers wrote. Other medications with point-of-sale prices above $10,000 were guselkumab ($11,511.52), tildrakizumab ($14,112.13), and risankizumab ($16,248.90).

The study was supported by grants from the Commonwealth Fund and the Leukemia & Lymphoma Society. One author disclosed receiving grants from Arnold Ventures, the Commonwealth Fund, and the Robert Wood Johnson Foundation for unrelated work, as well as honoraria from West Health and the Institute for Clinical and Economic Review.

During the annual meeting of the Society for Pediatric Dermatology, Amy S. Paller, MD, MS, marveled on the remarkable advances in the treatment of inflammatory skin disorders during the past 2 decades.

“We’ve come a long way, from disease features being red, thick, and scaly and being treated with nonspecific therapy like topical steroids, keratolytics, and tar, to understanding disease pathogenesis and finding new targeted therapies for inflammatory skin disorders in children,” said Dr. Paller, professor and chair of the department of dermatology at Northwestern University, Chicago. “There are now studies moving forward with gene correction, gene replacement, the gene product replaced, or pathway inhibition to prevent the effects of genetic change.”

Technology is leading the way in generating new therapeutic advances, she continued, beyond traditional “omics” to lipidomics, metabolomics, glycomics, and kinomics. “This has enabled us to find new genetic disorders and their causes, to look at changes in gene expression patterns, and to look at changes in protein expression patterns that give us clues as to how to move forward with better therapy,” she said. “When we’re talking about new insights into pathogenesis-based therapy, we’re talking largely about understanding the pathways that lead to either inflammation or promoting cell proliferation and abnormal differentiation.”

Treating pediatric psoriasis

Dr. Paller discussed her approach to managing patients with pediatric psoriasis, an inflammatory disorder with IL-23/Th17 skewing. “First of all, ask about itch and pain with these patients,” she advised. “Interviews have shown that 61% of children experience some itch, 39% have pain or stinging, and in the ixekizumab trials, 72% had what’s considered meaningful itch, with at least 4 out of 10 (mean intensity 5.3) on the itch numeric rating scale. Little is known about the itch associated with psoriasis and its underlying cause – unrelated to the IL-4/IL-13 pathway activation of atopic dermatitis – but it’s worth asking about. I find that itch of the scalp is especially a problem in psoriasis.”

Physicians should also ask pediatric psoriasis patients about joint pain, because about 1% of them have psoriatic arthritis, which is much less common than in adults, “but important to find and manage,” she added. Dr. Paller recommends the new R-JET rapid joint exam technique, which is accompanied by a three-question survey and body diagram that facilitates identification of true arthritis, “so you can know how quickly to refer”.

Several studies have described an increased risk of metabolic syndrome in adolescents with pediatric psoriasis and now in prepubertal children with the disease. In a recent study of 60 consecutive prepubertal children with psoriasis, 70% of whom had mild disease, 40% were overweight or obese, 53% had central obesity, 27% had high levels of the HOMA-IR (homeostasis model assessment of insulin resistance) despite generally normal levels of fasting glucose, and 30% met criteria for metabolic syndrome.

“This really struck me because our AAD [American Academy of Dermatology] guidelines did not recommend screening for type 2 diabetes in prepubertal children, even if overweight, because the risk is so small,” Dr. Paller said. “This report suggests that we may need to reconsider this recommendation in prepubertal children with psoriasis.”

Meanwhile, the number of medications approved by the Food and Drug Administration and the European Medicines Agency for children with psoriasis who are 6 years of age and above continues to expand, including tumor necrosis factor (TNF) inhibitors, interleukin (IL)-23 inhibitors, and IL-17 inhibitors. Most children can now achieve a PASI 90 within 12 weeks with the IL-23 inhibitor ustekinumab and the IL-17 inhibitors ixekizumab and secukinumab, Dr. Paller said.

In the ixekizumab trial, there are head-to-head comparison data in a European arm that involved the use of etanercept, she said. “What’s most noticeable is the significant difference in those who were able to achieve PASI 90 or above with this IL-17 inhibitor, versus etanercept,” which she added, raises the question of whether aiming for a PASI 75 is adequate, "or should we strive for PASI 90?” A pediatric psoriasis study published in 2020 found that the greatest improvement in quality of life was associated with a PASI 90 and use of systemic treatments (JAMA Dermatol. 2020;156[1]:72-8).

Looking forward, phase 3 clinical trials are underway in pediatric patients with moderate to severe psoriasis for guselkumab, tildrakizumab, risankizumab, certolizumab, bimekizumab, and brodalumab. “The cost of all of these biologics is high, however. I remind everyone that we still have methotrexate,” she said. “The risk of side effects with our low-dose methotrexate treatment for psoriasis remains low, but methotrexate doesn’t hit these [high] PASI numbers and it’s much slower in its onset than biologics.”

Dr. Paller disclosed that she is a consultant to and/or an investigator for AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, RAPT Therapeutics, Regeneron, and Sanofi.

Commentary by Robert Sidbury, MD, MPH

Dr. Paller reminds us of some essential features of pediatric psoriasis:
•    It can hurt. Ask your patients if it does.
•    It can itch. Look for excoriations, especially in the scalp.
•    It is often associated with metabolic syndrome, so check relevant biometrics and labs, and consider coincident insulin resistance.
•    Our traditional clinical trial target of PASI75, or a 75% reduction in body surface area involvement, is just not good enough. Studies have shown that the most meaningful quality-of-life gains come at PASI90 or above. 
•    With our newer biologics, such as IL-12/23 blockers (for instance, ustekinumab) and IL-17 blockers (for example, ixekizumab and secukinumab), PASI90 and better is a reasonable expectation, not a pipe dream. 

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

During the annual meeting of the Society for Pediatric Dermatology, Amy S. Paller, MD, MS, marveled on the remarkable advances in the treatment of inflammatory skin disorders during the past 2 decades.

“We’ve come a long way, from disease features being red, thick, and scaly and being treated with nonspecific therapy like topical steroids, keratolytics, and tar, to understanding disease pathogenesis and finding new targeted therapies for inflammatory skin disorders in children,” said Dr. Paller, professor and chair of the department of dermatology at Northwestern University, Chicago. “There are now studies moving forward with gene correction, gene replacement, the gene product replaced, or pathway inhibition to prevent the effects of genetic change.”

Technology is leading the way in generating new therapeutic advances, she continued, beyond traditional “omics” to lipidomics, metabolomics, glycomics, and kinomics. “This has enabled us to find new genetic disorders and their causes, to look at changes in gene expression patterns, and to look at changes in protein expression patterns that give us clues as to how to move forward with better therapy,” she said. “When we’re talking about new insights into pathogenesis-based therapy, we’re talking largely about understanding the pathways that lead to either inflammation or promoting cell proliferation and abnormal differentiation.”

Treating pediatric psoriasis

Dr. Paller discussed her approach to managing patients with pediatric psoriasis, an inflammatory disorder with IL-23/Th17 skewing. “First of all, ask about itch and pain with these patients,” she advised. “Interviews have shown that 61% of children experience some itch, 39% have pain or stinging, and in the ixekizumab trials, 72% had what’s considered meaningful itch, with at least 4 out of 10 (mean intensity 5.3) on the itch numeric rating scale. Little is known about the itch associated with psoriasis and its underlying cause – unrelated to the IL-4/IL-13 pathway activation of atopic dermatitis – but it’s worth asking about. I find that itch of the scalp is especially a problem in psoriasis.”

Physicians should also ask pediatric psoriasis patients about joint pain, because about 1% of them have psoriatic arthritis, which is much less common than in adults, “but important to find and manage,” she added. Dr. Paller recommends the new R-JET rapid joint exam technique, which is accompanied by a three-question survey and body diagram that facilitates identification of true arthritis, “so you can know how quickly to refer”.

Several studies have described an increased risk of metabolic syndrome in adolescents with pediatric psoriasis and now in prepubertal children with the disease. In a recent study of 60 consecutive prepubertal children with psoriasis, 70% of whom had mild disease, 40% were overweight or obese, 53% had central obesity, 27% had high levels of the HOMA-IR (homeostasis model assessment of insulin resistance) despite generally normal levels of fasting glucose, and 30% met criteria for metabolic syndrome.

“This really struck me because our AAD [American Academy of Dermatology] guidelines did not recommend screening for type 2 diabetes in prepubertal children, even if overweight, because the risk is so small,” Dr. Paller said. “This report suggests that we may need to reconsider this recommendation in prepubertal children with psoriasis.”

Meanwhile, the number of medications approved by the Food and Drug Administration and the European Medicines Agency for children with psoriasis who are 6 years of age and above continues to expand, including tumor necrosis factor (TNF) inhibitors, interleukin (IL)-23 inhibitors, and IL-17 inhibitors. Most children can now achieve a PASI 90 within 12 weeks with the IL-23 inhibitor ustekinumab and the IL-17 inhibitors ixekizumab and secukinumab, Dr. Paller said.

In the ixekizumab trial, there are head-to-head comparison data in a European arm that involved the use of etanercept, she said. “What’s most noticeable is the significant difference in those who were able to achieve PASI 90 or above with this IL-17 inhibitor, versus etanercept,” which she added, raises the question of whether aiming for a PASI 75 is adequate, "or should we strive for PASI 90?” A pediatric psoriasis study published in 2020 found that the greatest improvement in quality of life was associated with a PASI 90 and use of systemic treatments (JAMA Dermatol. 2020;156[1]:72-8).

Looking forward, phase 3 clinical trials are underway in pediatric patients with moderate to severe psoriasis for guselkumab, tildrakizumab, risankizumab, certolizumab, bimekizumab, and brodalumab. “The cost of all of these biologics is high, however. I remind everyone that we still have methotrexate,” she said. “The risk of side effects with our low-dose methotrexate treatment for psoriasis remains low, but methotrexate doesn’t hit these [high] PASI numbers and it’s much slower in its onset than biologics.”

Dr. Paller disclosed that she is a consultant to and/or an investigator for AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, RAPT Therapeutics, Regeneron, and Sanofi.

Commentary by Robert Sidbury, MD, MPH

Dr. Paller reminds us of some essential features of pediatric psoriasis:
•    It can hurt. Ask your patients if it does.
•    It can itch. Look for excoriations, especially in the scalp.
•    It is often associated with metabolic syndrome, so check relevant biometrics and labs, and consider coincident insulin resistance.
•    Our traditional clinical trial target of PASI75, or a 75% reduction in body surface area involvement, is just not good enough. Studies have shown that the most meaningful quality-of-life gains come at PASI90 or above. 
•    With our newer biologics, such as IL-12/23 blockers (for instance, ustekinumab) and IL-17 blockers (for example, ixekizumab and secukinumab), PASI90 and better is a reasonable expectation, not a pipe dream. 

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

During the annual meeting of the Society for Pediatric Dermatology, Amy S. Paller, MD, MS, marveled on the remarkable advances in the treatment of inflammatory skin disorders during the past 2 decades.

“We’ve come a long way, from disease features being red, thick, and scaly and being treated with nonspecific therapy like topical steroids, keratolytics, and tar, to understanding disease pathogenesis and finding new targeted therapies for inflammatory skin disorders in children,” said Dr. Paller, professor and chair of the department of dermatology at Northwestern University, Chicago. “There are now studies moving forward with gene correction, gene replacement, the gene product replaced, or pathway inhibition to prevent the effects of genetic change.”

Technology is leading the way in generating new therapeutic advances, she continued, beyond traditional “omics” to lipidomics, metabolomics, glycomics, and kinomics. “This has enabled us to find new genetic disorders and their causes, to look at changes in gene expression patterns, and to look at changes in protein expression patterns that give us clues as to how to move forward with better therapy,” she said. “When we’re talking about new insights into pathogenesis-based therapy, we’re talking largely about understanding the pathways that lead to either inflammation or promoting cell proliferation and abnormal differentiation.”

Treating pediatric psoriasis

Dr. Paller discussed her approach to managing patients with pediatric psoriasis, an inflammatory disorder with IL-23/Th17 skewing. “First of all, ask about itch and pain with these patients,” she advised. “Interviews have shown that 61% of children experience some itch, 39% have pain or stinging, and in the ixekizumab trials, 72% had what’s considered meaningful itch, with at least 4 out of 10 (mean intensity 5.3) on the itch numeric rating scale. Little is known about the itch associated with psoriasis and its underlying cause – unrelated to the IL-4/IL-13 pathway activation of atopic dermatitis – but it’s worth asking about. I find that itch of the scalp is especially a problem in psoriasis.”

Physicians should also ask pediatric psoriasis patients about joint pain, because about 1% of them have psoriatic arthritis, which is much less common than in adults, “but important to find and manage,” she added. Dr. Paller recommends the new R-JET rapid joint exam technique, which is accompanied by a three-question survey and body diagram that facilitates identification of true arthritis, “so you can know how quickly to refer”.

Several studies have described an increased risk of metabolic syndrome in adolescents with pediatric psoriasis and now in prepubertal children with the disease. In a recent study of 60 consecutive prepubertal children with psoriasis, 70% of whom had mild disease, 40% were overweight or obese, 53% had central obesity, 27% had high levels of the HOMA-IR (homeostasis model assessment of insulin resistance) despite generally normal levels of fasting glucose, and 30% met criteria for metabolic syndrome.

“This really struck me because our AAD [American Academy of Dermatology] guidelines did not recommend screening for type 2 diabetes in prepubertal children, even if overweight, because the risk is so small,” Dr. Paller said. “This report suggests that we may need to reconsider this recommendation in prepubertal children with psoriasis.”

Meanwhile, the number of medications approved by the Food and Drug Administration and the European Medicines Agency for children with psoriasis who are 6 years of age and above continues to expand, including tumor necrosis factor (TNF) inhibitors, interleukin (IL)-23 inhibitors, and IL-17 inhibitors. Most children can now achieve a PASI 90 within 12 weeks with the IL-23 inhibitor ustekinumab and the IL-17 inhibitors ixekizumab and secukinumab, Dr. Paller said.

In the ixekizumab trial, there are head-to-head comparison data in a European arm that involved the use of etanercept, she said. “What’s most noticeable is the significant difference in those who were able to achieve PASI 90 or above with this IL-17 inhibitor, versus etanercept,” which she added, raises the question of whether aiming for a PASI 75 is adequate, "or should we strive for PASI 90?” A pediatric psoriasis study published in 2020 found that the greatest improvement in quality of life was associated with a PASI 90 and use of systemic treatments (JAMA Dermatol. 2020;156[1]:72-8).

Looking forward, phase 3 clinical trials are underway in pediatric patients with moderate to severe psoriasis for guselkumab, tildrakizumab, risankizumab, certolizumab, bimekizumab, and brodalumab. “The cost of all of these biologics is high, however. I remind everyone that we still have methotrexate,” she said. “The risk of side effects with our low-dose methotrexate treatment for psoriasis remains low, but methotrexate doesn’t hit these [high] PASI numbers and it’s much slower in its onset than biologics.”

Dr. Paller disclosed that she is a consultant to and/or an investigator for AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, RAPT Therapeutics, Regeneron, and Sanofi.

Commentary by Robert Sidbury, MD, MPH

Dr. Paller reminds us of some essential features of pediatric psoriasis:
•    It can hurt. Ask your patients if it does.
•    It can itch. Look for excoriations, especially in the scalp.
•    It is often associated with metabolic syndrome, so check relevant biometrics and labs, and consider coincident insulin resistance.
•    Our traditional clinical trial target of PASI75, or a 75% reduction in body surface area involvement, is just not good enough. Studies have shown that the most meaningful quality-of-life gains come at PASI90 or above. 
•    With our newer biologics, such as IL-12/23 blockers (for instance, ustekinumab) and IL-17 blockers (for example, ixekizumab and secukinumab), PASI90 and better is a reasonable expectation, not a pipe dream. 

Dr. Sidbury is chief of dermatology at Seattle Children's Hospital and professor, department of pediatrics, University of Washington, Seattle. He is a site principal investigator for dupilumab trials, for which the hospital has a contract with Regeneron.

This article was updated 6/16/22.

Several recent studies have evaluated that association between psoriasis and known comorbidities including cardiovascular disease, non-alcoholic fatty liver disease (NAFLD), and malignancy. Several recent studies have added to our understanding of the relationship between these conditions.

Using the largest database of hospitalized patients in the United States, Edgen et al found that hospitalization rates for patients with psoriasis are increasing. While the proportion of patients with psoriasis hospitalized with psoriasis as a primary diagnosis decreased about four-fold over a 20-year period (1999-2018), incidence of hospitalizations with any diagnosis of psoriasis has increased. Hospitalized psoriasis patients are increasingly more likely to have other comorbid conditions as during the study period the proportion of hospitalized psoriasis patients with a Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9%. Psoriasis severity, medication use, and reasons for hospitalization were not reported. The authors suggest that screening and management of comorbidities in the outpatient setting may help reduce preventable psoriasis hospitalizations.

Both NAFLD and cardiovascular disease are well-known psoriasis comorbidities, Gonzalez-Cantaro et al studied two cohorts of patients to better define the relationship between these two conditions. In a European cohort of 76 psoriasis patients and 76 control patients, psoriasis patients with NAFLD had a higher prevalence of subclinical atherosclerosis than both psoriasis patients without NAFLD (61% vs 23%) and age, sex, and BMI-matched controls with NAFLD (61% vs 32%). Psoriasis patients were also more likely that control patients to have insulin resistance, higher weight circumference, and dysplipidemia. Among 162 psoriasis patients who underwent PET and coronary CT angiography, higher hepatic FDG uptake (indicating NAFLD) was associated higher atherosclerotic disease burden. Importantly, both the NAFLD and CAD were subclinical in these patients. While the cross-sectional study design precludes any conclusions about causality, physicians should be aware that these two comorbidities are related. Lower waist circumference and greater physical activity were both associated with lower rates of NAFLD among patients with psoriasis, providing some guidance for counseling patients.

Several recent studies have found that cancer rates among patients with psoriasis are higher than what is observed in the general population. The association of psoriasis with lymphohematologic malignancies (LHM) has been controversial. A systematic review and meta-analysis of 25 observational studies including over 2.5 million subjects (Bellinato et al.) found a 1.55-fold increased risk of LHM in patients with moderate to severe psoriasis. Strikingly, the risk of cutaneous T cell lymphoma (CTCL) was increased 6.22-fold, with more severe psoriasis being associated with the highest risk of CTCL. A causal relationship cannot be established from this type of studies, but the authors hypothesize that drugs used to treat psoriasis or the chronic T cell activation caused by active disease may contribute to the risk of LMH. Additionally, psoriasis and CTCL can share clinical features and some cases may be due to misdiagnosis. Interestingly, two psoriasis comorbities, diabetes and obesity, are also associated with an increased risk of LHM.

Early identification and management of comorbidities can help in reducing morbidity and mortality. With so many psoriasis treatments available, understanding how different therapies may impact comorbid conditions is important in helping dermatologists to choose the best therapy for each individual patient.

Several recent studies have evaluated that association between psoriasis and known comorbidities including cardiovascular disease, non-alcoholic fatty liver disease (NAFLD), and malignancy. Several recent studies have added to our understanding of the relationship between these conditions.

Using the largest database of hospitalized patients in the United States, Edgen et al found that hospitalization rates for patients with psoriasis are increasing. While the proportion of patients with psoriasis hospitalized with psoriasis as a primary diagnosis decreased about four-fold over a 20-year period (1999-2018), incidence of hospitalizations with any diagnosis of psoriasis has increased. Hospitalized psoriasis patients are increasingly more likely to have other comorbid conditions as during the study period the proportion of hospitalized psoriasis patients with a Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9%. Psoriasis severity, medication use, and reasons for hospitalization were not reported. The authors suggest that screening and management of comorbidities in the outpatient setting may help reduce preventable psoriasis hospitalizations.

Both NAFLD and cardiovascular disease are well-known psoriasis comorbidities, Gonzalez-Cantaro et al studied two cohorts of patients to better define the relationship between these two conditions. In a European cohort of 76 psoriasis patients and 76 control patients, psoriasis patients with NAFLD had a higher prevalence of subclinical atherosclerosis than both psoriasis patients without NAFLD (61% vs 23%) and age, sex, and BMI-matched controls with NAFLD (61% vs 32%). Psoriasis patients were also more likely that control patients to have insulin resistance, higher weight circumference, and dysplipidemia. Among 162 psoriasis patients who underwent PET and coronary CT angiography, higher hepatic FDG uptake (indicating NAFLD) was associated higher atherosclerotic disease burden. Importantly, both the NAFLD and CAD were subclinical in these patients. While the cross-sectional study design precludes any conclusions about causality, physicians should be aware that these two comorbidities are related. Lower waist circumference and greater physical activity were both associated with lower rates of NAFLD among patients with psoriasis, providing some guidance for counseling patients.

Several recent studies have found that cancer rates among patients with psoriasis are higher than what is observed in the general population. The association of psoriasis with lymphohematologic malignancies (LHM) has been controversial. A systematic review and meta-analysis of 25 observational studies including over 2.5 million subjects (Bellinato et al.) found a 1.55-fold increased risk of LHM in patients with moderate to severe psoriasis. Strikingly, the risk of cutaneous T cell lymphoma (CTCL) was increased 6.22-fold, with more severe psoriasis being associated with the highest risk of CTCL. A causal relationship cannot be established from this type of studies, but the authors hypothesize that drugs used to treat psoriasis or the chronic T cell activation caused by active disease may contribute to the risk of LMH. Additionally, psoriasis and CTCL can share clinical features and some cases may be due to misdiagnosis. Interestingly, two psoriasis comorbities, diabetes and obesity, are also associated with an increased risk of LHM.

Early identification and management of comorbidities can help in reducing morbidity and mortality. With so many psoriasis treatments available, understanding how different therapies may impact comorbid conditions is important in helping dermatologists to choose the best therapy for each individual patient.

Several recent studies have evaluated that association between psoriasis and known comorbidities including cardiovascular disease, non-alcoholic fatty liver disease (NAFLD), and malignancy. Several recent studies have added to our understanding of the relationship between these conditions.

Using the largest database of hospitalized patients in the United States, Edgen et al found that hospitalization rates for patients with psoriasis are increasing. While the proportion of patients with psoriasis hospitalized with psoriasis as a primary diagnosis decreased about four-fold over a 20-year period (1999-2018), incidence of hospitalizations with any diagnosis of psoriasis has increased. Hospitalized psoriasis patients are increasingly more likely to have other comorbid conditions as during the study period the proportion of hospitalized psoriasis patients with a Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9%. Psoriasis severity, medication use, and reasons for hospitalization were not reported. The authors suggest that screening and management of comorbidities in the outpatient setting may help reduce preventable psoriasis hospitalizations.

Both NAFLD and cardiovascular disease are well-known psoriasis comorbidities, Gonzalez-Cantaro et al studied two cohorts of patients to better define the relationship between these two conditions. In a European cohort of 76 psoriasis patients and 76 control patients, psoriasis patients with NAFLD had a higher prevalence of subclinical atherosclerosis than both psoriasis patients without NAFLD (61% vs 23%) and age, sex, and BMI-matched controls with NAFLD (61% vs 32%). Psoriasis patients were also more likely that control patients to have insulin resistance, higher weight circumference, and dysplipidemia. Among 162 psoriasis patients who underwent PET and coronary CT angiography, higher hepatic FDG uptake (indicating NAFLD) was associated higher atherosclerotic disease burden. Importantly, both the NAFLD and CAD were subclinical in these patients. While the cross-sectional study design precludes any conclusions about causality, physicians should be aware that these two comorbidities are related. Lower waist circumference and greater physical activity were both associated with lower rates of NAFLD among patients with psoriasis, providing some guidance for counseling patients.

Several recent studies have found that cancer rates among patients with psoriasis are higher than what is observed in the general population. The association of psoriasis with lymphohematologic malignancies (LHM) has been controversial. A systematic review and meta-analysis of 25 observational studies including over 2.5 million subjects (Bellinato et al.) found a 1.55-fold increased risk of LHM in patients with moderate to severe psoriasis. Strikingly, the risk of cutaneous T cell lymphoma (CTCL) was increased 6.22-fold, with more severe psoriasis being associated with the highest risk of CTCL. A causal relationship cannot be established from this type of studies, but the authors hypothesize that drugs used to treat psoriasis or the chronic T cell activation caused by active disease may contribute to the risk of LMH. Additionally, psoriasis and CTCL can share clinical features and some cases may be due to misdiagnosis. Interestingly, two psoriasis comorbities, diabetes and obesity, are also associated with an increased risk of LHM.

Early identification and management of comorbidities can help in reducing morbidity and mortality. With so many psoriasis treatments available, understanding how different therapies may impact comorbid conditions is important in helping dermatologists to choose the best therapy for each individual patient.

Receiving treatment with a biologic medication, compared with no biologic treatment, appeared to be associated with a lower risk for developing psoriatic arthritis (PsA) in patients with psoriasis.

That’s according to the results of a nested case-control study involving electronic medical record data from an Israeli health maintenance organization in Arthritis & Rheumatology. Compared with no biologic treatment, the risk for developing PsA among PsO patients was reduced by 39%.

This study shows “a statistically and clinically significant lower risk for developing PsA among patients receiving biologic medications for psoriasis treatment,” wrote Yael Shalev Rosenthal, MPH, of the Sackler Faculty of Medicine, Tel Aviv University and colleagues. “The results suggest considering treatment with biologic medications in patients [who] present with significant risk factors for PsA at an earlier stage of treatment.”

“It would be nice to believe this story, but I don’t think we can based on the evidence we’ve got so far,” commented Philip Helliwell, PhD, DM, in an interview.

Dr. Helliwell, who is professor of clinical rheumatology at the University of Leeds (England) and an Honorary Consultant Rheumatologist for the Leeds Teaching Hospitals and Bradford Teaching Hospitals NHS Trust, noted that there were several issues with the current evidence.

Aside from their often retrospective or nonrandomized nature, prior analyses, including the current one, were based on EMR data.

“There’s actually no face-to-face patient contact going on here. It’s all done on coding, and coding can be unreliable,” Dr. Helliwell said.

While the study’s findings are “in line with other studies that have looked at this, and suggest that if you get a biologic, you’re less likely to get PsA with your psoriasis, there could be lots of reasons why.”

The big problem here is confounding by indication. “You don’t get on a biologic unless you’ve got bad psoriasis,” Dr. Helliwell explained. The Israeli criteria for starting a biologic are much higher than in the United Kingdom, he added, requiring more than 50% of patients’ body surface area to be affected, or a Psoriasis Area and Severity Index score of more than 50. Moreover, people with bad psoriasis are more likely to get PsA. This, however, makes the results more impressive.

Confounding by indication is an issue with this study, agreed consultant rheumatologist Adewale Adebajo, PhD, in a separate interview. He acknowledged, however, that the study’s authors did try to account for this by limiting the timescale of their analysis to the first 10 years of biologic therapy. They also used the usual methods of propensity score matching and multivariate Cox regression analysis to hopefully iron out any differences between the two groups of patients.

Study details and results

Ms. Rosenthal and coauthors analyzed EMR data on patients with psoriasis but not PsA that were logged in the Maccabi Healthcare Services (MHS) database. The MHS is the second-largest health maintenance organization in Israel, insuring over 2 million members, the researchers said.

In all, 663 patients with psoriasis but not PsA before or at initiation of biologic treatment were included in their analysis and matched to a control group of 663 patients with psoriasis who had not received biologic treatment. Propensity score matching was used to iron out some differences in baseline characteristics that had been seen between the groups, such as older age at diagnosis, higher body mass index, and a longer time between diagnosis and treatment seen in patients treated without biologics.

After adjusting for multiple risk factors and confounders, “the control group still had a significantly higher risk for PsA, compared to the biological treatment group,” the researchers wrote. Indeed, the adjusted hazard ratio was 1.39, with a 95% confidence interval between 1.03 and 1.87.

An ‘intriguing study’

“This is a retrospective study, and it has all the faults of a retrospective study,” said Dr. Adebajo, associate medical director for research and development at Barnsley (England) NHS Foundation Trust. But “these were patients who hopefully hadn’t yet developed psoriatic arthritis, although it is difficult to exclude subclinical psoriatic arthritis.”

The ideal would of course be to look at patients prospectively, but a randomized clinical trial would be unlikely to ever be conducted, Dr. Helliwell noted. “It would be unfair to randomize people who have got bad psoriasis and need a biologic to placebo just to prove the point really,” he said. “Getting control groups in this arena is very difficult.”

That doesn’t mean that prospective evaluation is not possible. Dr. Adebajo noted that there were already cohorts of newly diagnosed patients who were being prospectively followed up and those could perhaps be used to look at the question again in the future.

“You’re then looking at the natural history, the natural outcome, and you don’t need to worry about confounding because you’re just collecting all of the information as you go along.”

The idea that biologics might slow or even prevent the onset of PsA is “an interesting and enchanting hypothesis,” Dr. Adebajo said. “The study doesn’t prove the hypothesis, but it’s an intriguing study because it doesn’t disprove the hypothesis either.

“It gives us food for thought and a basis for further studies,” as well as some “encouragement to perhaps use biologics earlier because there may be additional benefits of doing so.”

That’s still to be proven of course, as it has been reported that patients with psoriasis can develop PsA while taking biologics.

“Clinically, that’s what we see in the combined clinic. We get people referred with psoriasis [who are] already on a biologic who developed musculoskeletal problems,” Dr. Helliwell said.

“It would be nice to believe” that biologics prevent or slow PsA in patients with psoriasis, Dr. Helliwell added, but I’m not sure these data are conclusive. From this study we know nothing about the phenotype of psoriasis, which is important in the development of PsA. In addition, we know that of the 30% of people with psoriasis who develop PsA, about half of these are undiagnosed at the time of such studies. In that case, what the biologic is doing is just treating preexisting PsA. If you count those numbers up, some of the differences between the two groups seen in this study are accounted for. From registry data there is no way of checking this.”

No external funding was used for the study. One author acknowledged acting as an investigator, adviser, or consultant to several pharmaceutical companies including AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Coherus, Dexcel Pharma, Eli Lilly, Janssen, Novartis, and Pfizer. All other authors had nothing to disclose.

Dr. Helliwell and Dr. Adebajo had no conflicts of interest.

Receiving treatment with a biologic medication, compared with no biologic treatment, appeared to be associated with a lower risk for developing psoriatic arthritis (PsA) in patients with psoriasis.

That’s according to the results of a nested case-control study involving electronic medical record data from an Israeli health maintenance organization in Arthritis & Rheumatology. Compared with no biologic treatment, the risk for developing PsA among PsO patients was reduced by 39%.

This study shows “a statistically and clinically significant lower risk for developing PsA among patients receiving biologic medications for psoriasis treatment,” wrote Yael Shalev Rosenthal, MPH, of the Sackler Faculty of Medicine, Tel Aviv University and colleagues. “The results suggest considering treatment with biologic medications in patients [who] present with significant risk factors for PsA at an earlier stage of treatment.”

“It would be nice to believe this story, but I don’t think we can based on the evidence we’ve got so far,” commented Philip Helliwell, PhD, DM, in an interview.

Dr. Helliwell, who is professor of clinical rheumatology at the University of Leeds (England) and an Honorary Consultant Rheumatologist for the Leeds Teaching Hospitals and Bradford Teaching Hospitals NHS Trust, noted that there were several issues with the current evidence.

Aside from their often retrospective or nonrandomized nature, prior analyses, including the current one, were based on EMR data.

“There’s actually no face-to-face patient contact going on here. It’s all done on coding, and coding can be unreliable,” Dr. Helliwell said.

While the study’s findings are “in line with other studies that have looked at this, and suggest that if you get a biologic, you’re less likely to get PsA with your psoriasis, there could be lots of reasons why.”

The big problem here is confounding by indication. “You don’t get on a biologic unless you’ve got bad psoriasis,” Dr. Helliwell explained. The Israeli criteria for starting a biologic are much higher than in the United Kingdom, he added, requiring more than 50% of patients’ body surface area to be affected, or a Psoriasis Area and Severity Index score of more than 50. Moreover, people with bad psoriasis are more likely to get PsA. This, however, makes the results more impressive.

Confounding by indication is an issue with this study, agreed consultant rheumatologist Adewale Adebajo, PhD, in a separate interview. He acknowledged, however, that the study’s authors did try to account for this by limiting the timescale of their analysis to the first 10 years of biologic therapy. They also used the usual methods of propensity score matching and multivariate Cox regression analysis to hopefully iron out any differences between the two groups of patients.

Study details and results

Ms. Rosenthal and coauthors analyzed EMR data on patients with psoriasis but not PsA that were logged in the Maccabi Healthcare Services (MHS) database. The MHS is the second-largest health maintenance organization in Israel, insuring over 2 million members, the researchers said.

In all, 663 patients with psoriasis but not PsA before or at initiation of biologic treatment were included in their analysis and matched to a control group of 663 patients with psoriasis who had not received biologic treatment. Propensity score matching was used to iron out some differences in baseline characteristics that had been seen between the groups, such as older age at diagnosis, higher body mass index, and a longer time between diagnosis and treatment seen in patients treated without biologics.

After adjusting for multiple risk factors and confounders, “the control group still had a significantly higher risk for PsA, compared to the biological treatment group,” the researchers wrote. Indeed, the adjusted hazard ratio was 1.39, with a 95% confidence interval between 1.03 and 1.87.

An ‘intriguing study’

“This is a retrospective study, and it has all the faults of a retrospective study,” said Dr. Adebajo, associate medical director for research and development at Barnsley (England) NHS Foundation Trust. But “these were patients who hopefully hadn’t yet developed psoriatic arthritis, although it is difficult to exclude subclinical psoriatic arthritis.”

The ideal would of course be to look at patients prospectively, but a randomized clinical trial would be unlikely to ever be conducted, Dr. Helliwell noted. “It would be unfair to randomize people who have got bad psoriasis and need a biologic to placebo just to prove the point really,” he said. “Getting control groups in this arena is very difficult.”

That doesn’t mean that prospective evaluation is not possible. Dr. Adebajo noted that there were already cohorts of newly diagnosed patients who were being prospectively followed up and those could perhaps be used to look at the question again in the future.

“You’re then looking at the natural history, the natural outcome, and you don’t need to worry about confounding because you’re just collecting all of the information as you go along.”

The idea that biologics might slow or even prevent the onset of PsA is “an interesting and enchanting hypothesis,” Dr. Adebajo said. “The study doesn’t prove the hypothesis, but it’s an intriguing study because it doesn’t disprove the hypothesis either.

“It gives us food for thought and a basis for further studies,” as well as some “encouragement to perhaps use biologics earlier because there may be additional benefits of doing so.”

That’s still to be proven of course, as it has been reported that patients with psoriasis can develop PsA while taking biologics.

“Clinically, that’s what we see in the combined clinic. We get people referred with psoriasis [who are] already on a biologic who developed musculoskeletal problems,” Dr. Helliwell said.

“It would be nice to believe” that biologics prevent or slow PsA in patients with psoriasis, Dr. Helliwell added, but I’m not sure these data are conclusive. From this study we know nothing about the phenotype of psoriasis, which is important in the development of PsA. In addition, we know that of the 30% of people with psoriasis who develop PsA, about half of these are undiagnosed at the time of such studies. In that case, what the biologic is doing is just treating preexisting PsA. If you count those numbers up, some of the differences between the two groups seen in this study are accounted for. From registry data there is no way of checking this.”

No external funding was used for the study. One author acknowledged acting as an investigator, adviser, or consultant to several pharmaceutical companies including AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Coherus, Dexcel Pharma, Eli Lilly, Janssen, Novartis, and Pfizer. All other authors had nothing to disclose.

Dr. Helliwell and Dr. Adebajo had no conflicts of interest.

Receiving treatment with a biologic medication, compared with no biologic treatment, appeared to be associated with a lower risk for developing psoriatic arthritis (PsA) in patients with psoriasis.

That’s according to the results of a nested case-control study involving electronic medical record data from an Israeli health maintenance organization in Arthritis & Rheumatology. Compared with no biologic treatment, the risk for developing PsA among PsO patients was reduced by 39%.

This study shows “a statistically and clinically significant lower risk for developing PsA among patients receiving biologic medications for psoriasis treatment,” wrote Yael Shalev Rosenthal, MPH, of the Sackler Faculty of Medicine, Tel Aviv University and colleagues. “The results suggest considering treatment with biologic medications in patients [who] present with significant risk factors for PsA at an earlier stage of treatment.”

“It would be nice to believe this story, but I don’t think we can based on the evidence we’ve got so far,” commented Philip Helliwell, PhD, DM, in an interview.

Dr. Helliwell, who is professor of clinical rheumatology at the University of Leeds (England) and an Honorary Consultant Rheumatologist for the Leeds Teaching Hospitals and Bradford Teaching Hospitals NHS Trust, noted that there were several issues with the current evidence.

Aside from their often retrospective or nonrandomized nature, prior analyses, including the current one, were based on EMR data.

“There’s actually no face-to-face patient contact going on here. It’s all done on coding, and coding can be unreliable,” Dr. Helliwell said.

While the study’s findings are “in line with other studies that have looked at this, and suggest that if you get a biologic, you’re less likely to get PsA with your psoriasis, there could be lots of reasons why.”

The big problem here is confounding by indication. “You don’t get on a biologic unless you’ve got bad psoriasis,” Dr. Helliwell explained. The Israeli criteria for starting a biologic are much higher than in the United Kingdom, he added, requiring more than 50% of patients’ body surface area to be affected, or a Psoriasis Area and Severity Index score of more than 50. Moreover, people with bad psoriasis are more likely to get PsA. This, however, makes the results more impressive.

Confounding by indication is an issue with this study, agreed consultant rheumatologist Adewale Adebajo, PhD, in a separate interview. He acknowledged, however, that the study’s authors did try to account for this by limiting the timescale of their analysis to the first 10 years of biologic therapy. They also used the usual methods of propensity score matching and multivariate Cox regression analysis to hopefully iron out any differences between the two groups of patients.

Study details and results

Ms. Rosenthal and coauthors analyzed EMR data on patients with psoriasis but not PsA that were logged in the Maccabi Healthcare Services (MHS) database. The MHS is the second-largest health maintenance organization in Israel, insuring over 2 million members, the researchers said.

In all, 663 patients with psoriasis but not PsA before or at initiation of biologic treatment were included in their analysis and matched to a control group of 663 patients with psoriasis who had not received biologic treatment. Propensity score matching was used to iron out some differences in baseline characteristics that had been seen between the groups, such as older age at diagnosis, higher body mass index, and a longer time between diagnosis and treatment seen in patients treated without biologics.

After adjusting for multiple risk factors and confounders, “the control group still had a significantly higher risk for PsA, compared to the biological treatment group,” the researchers wrote. Indeed, the adjusted hazard ratio was 1.39, with a 95% confidence interval between 1.03 and 1.87.

An ‘intriguing study’

“This is a retrospective study, and it has all the faults of a retrospective study,” said Dr. Adebajo, associate medical director for research and development at Barnsley (England) NHS Foundation Trust. But “these were patients who hopefully hadn’t yet developed psoriatic arthritis, although it is difficult to exclude subclinical psoriatic arthritis.”

The ideal would of course be to look at patients prospectively, but a randomized clinical trial would be unlikely to ever be conducted, Dr. Helliwell noted. “It would be unfair to randomize people who have got bad psoriasis and need a biologic to placebo just to prove the point really,” he said. “Getting control groups in this arena is very difficult.”

That doesn’t mean that prospective evaluation is not possible. Dr. Adebajo noted that there were already cohorts of newly diagnosed patients who were being prospectively followed up and those could perhaps be used to look at the question again in the future.

“You’re then looking at the natural history, the natural outcome, and you don’t need to worry about confounding because you’re just collecting all of the information as you go along.”

The idea that biologics might slow or even prevent the onset of PsA is “an interesting and enchanting hypothesis,” Dr. Adebajo said. “The study doesn’t prove the hypothesis, but it’s an intriguing study because it doesn’t disprove the hypothesis either.

“It gives us food for thought and a basis for further studies,” as well as some “encouragement to perhaps use biologics earlier because there may be additional benefits of doing so.”

That’s still to be proven of course, as it has been reported that patients with psoriasis can develop PsA while taking biologics.

“Clinically, that’s what we see in the combined clinic. We get people referred with psoriasis [who are] already on a biologic who developed musculoskeletal problems,” Dr. Helliwell said.

“It would be nice to believe” that biologics prevent or slow PsA in patients with psoriasis, Dr. Helliwell added, but I’m not sure these data are conclusive. From this study we know nothing about the phenotype of psoriasis, which is important in the development of PsA. In addition, we know that of the 30% of people with psoriasis who develop PsA, about half of these are undiagnosed at the time of such studies. In that case, what the biologic is doing is just treating preexisting PsA. If you count those numbers up, some of the differences between the two groups seen in this study are accounted for. From registry data there is no way of checking this.”

No external funding was used for the study. One author acknowledged acting as an investigator, adviser, or consultant to several pharmaceutical companies including AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Coherus, Dexcel Pharma, Eli Lilly, Janssen, Novartis, and Pfizer. All other authors had nothing to disclose.

Dr. Helliwell and Dr. Adebajo had no conflicts of interest.

Key clinical point: Although rates of principal psoriasis hospitalizations have decreased among patients with psoriasis in the last 2 decades in the United States, hospitalization for non-psoriatic reasons has increased, which may be attributed to increased comorbidity burden driving admissions because of comorbidities.

Major finding: Between 1998 and 2018, the incidence of hospitalizations with either principal or secondary diagnosis of psoriasis increased from 17.9 to 52.0 per 100,000 persons, the proportion of patients with psoriasis hospitalized with psoriasis as principal diagnosis reduced from 4.1% to 1.0%, and those with Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9% (all adjusted P-trend < .0001).

Study details: This was a 21-year longitudinal trend analysis of the National Inpatient Sample database between 1998 and 2018 including adults with a principal or secondary diagnosis of psoriasis.

Disclosures: The study did not receive any funding. The authors declared no conflict of interests.

Source: Edigin E et al. J Eur Acad Dermatol Venereol. 2021 Aug 9. doi: 10.1111/jdv.17590.

Key clinical point: Although rates of principal psoriasis hospitalizations have decreased among patients with psoriasis in the last 2 decades in the United States, hospitalization for non-psoriatic reasons has increased, which may be attributed to increased comorbidity burden driving admissions because of comorbidities.

Major finding: Between 1998 and 2018, the incidence of hospitalizations with either principal or secondary diagnosis of psoriasis increased from 17.9 to 52.0 per 100,000 persons, the proportion of patients with psoriasis hospitalized with psoriasis as principal diagnosis reduced from 4.1% to 1.0%, and those with Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9% (all adjusted P-trend < .0001).

Study details: This was a 21-year longitudinal trend analysis of the National Inpatient Sample database between 1998 and 2018 including adults with a principal or secondary diagnosis of psoriasis.

Disclosures: The study did not receive any funding. The authors declared no conflict of interests.

Source: Edigin E et al. J Eur Acad Dermatol Venereol. 2021 Aug 9. doi: 10.1111/jdv.17590.

Key clinical point: Although rates of principal psoriasis hospitalizations have decreased among patients with psoriasis in the last 2 decades in the United States, hospitalization for non-psoriatic reasons has increased, which may be attributed to increased comorbidity burden driving admissions because of comorbidities.

Major finding: Between 1998 and 2018, the incidence of hospitalizations with either principal or secondary diagnosis of psoriasis increased from 17.9 to 52.0 per 100,000 persons, the proportion of patients with psoriasis hospitalized with psoriasis as principal diagnosis reduced from 4.1% to 1.0%, and those with Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9% (all adjusted P-trend < .0001).

Study details: This was a 21-year longitudinal trend analysis of the National Inpatient Sample database between 1998 and 2018 including adults with a principal or secondary diagnosis of psoriasis.

Disclosures: The study did not receive any funding. The authors declared no conflict of interests.

Source: Edigin E et al. J Eur Acad Dermatol Venereol. 2021 Aug 9. doi: 10.1111/jdv.17590.

Key clinical point: A significant relation was observed between low hemoglobin levels and increased risk for psoriasis in patients with chronic kidney disease (CKD), indicating that proactive treatment for inflammation might help manage both anemia and psoriasis in patients with CKD.

Major finding: During a mean follow-up period of 6.16±1.02 years, 2.39% of patients with CKD developed psoriasis with cumulative incidence higher in patients with vs without anemia (P less than .0001). The risk for psoriasis was significantly higher in patients with vs without anemia (adjusted hazard ratio, 1.109; P < .0001).

Study details: Findings are from a retrospective cohort study of 576,461 patients with CKD.

Disclosures: This study was supported by a National Research Foundation of Korea grant funded by the Korean government. The authors declare no competing interests.

Source: Lee SH et al. Sci Rep. 2021 Jul 20. doi: 10.1038/s41598-021-94165-w.

Key clinical point: A significant relation was observed between low hemoglobin levels and increased risk for psoriasis in patients with chronic kidney disease (CKD), indicating that proactive treatment for inflammation might help manage both anemia and psoriasis in patients with CKD.

Major finding: During a mean follow-up period of 6.16±1.02 years, 2.39% of patients with CKD developed psoriasis with cumulative incidence higher in patients with vs without anemia (P less than .0001). The risk for psoriasis was significantly higher in patients with vs without anemia (adjusted hazard ratio, 1.109; P < .0001).

Study details: Findings are from a retrospective cohort study of 576,461 patients with CKD.

Disclosures: This study was supported by a National Research Foundation of Korea grant funded by the Korean government. The authors declare no competing interests.

Source: Lee SH et al. Sci Rep. 2021 Jul 20. doi: 10.1038/s41598-021-94165-w.

Key clinical point: A significant relation was observed between low hemoglobin levels and increased risk for psoriasis in patients with chronic kidney disease (CKD), indicating that proactive treatment for inflammation might help manage both anemia and psoriasis in patients with CKD.

Major finding: During a mean follow-up period of 6.16±1.02 years, 2.39% of patients with CKD developed psoriasis with cumulative incidence higher in patients with vs without anemia (P less than .0001). The risk for psoriasis was significantly higher in patients with vs without anemia (adjusted hazard ratio, 1.109; P < .0001).

Study details: Findings are from a retrospective cohort study of 576,461 patients with CKD.

Disclosures: This study was supported by a National Research Foundation of Korea grant funded by the Korean government. The authors declare no competing interests.

Source: Lee SH et al. Sci Rep. 2021 Jul 20. doi: 10.1038/s41598-021-94165-w.

Key clinical point: Long-term proactive management (PM) of psoriasis with calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) vs reactive management (RM) benefitted all patients irrespective of baseline characteristics, with greater benefits observed in patients with more severe disease.

Major finding: Effect of treatment on time to first relapse was consistent across all baseline parameters, with treatment group (PM vs RM; hazard ratio [HR], 0.56; P less than .001), baseline Physician Global Assessment (severe vs mild; HR, 2.32; P = .003), and modified Psoriasis Area Severity Index (severe vs mild; HR, 1.77; P = .002) having a significant impact.

Study details: This was a post hoc analysis of phase 3 PSO LONG trial which included a 52-week maintenance phase where patients with psoriasis were randomly assigned to Cal/BD twice weekly (PM) or vehicle foam (RM).

Disclosures: This study was supported by LEO Pharma, Ballerup, Denmark. MG Lebwohl, KA Papp, and RB Warren declared receiving research funds, honoraria for advisory board, speaker, and/or consultant services from various sources including LEO Pharma. MH Mørch and MYJ Bernasconi declared being employees of LEO Pharma.

Source: Lebwohl MG et al. Dermatol Ther (Heidelb). 2021 Aug 2. doi: 10.1007/s13555-021-00585-x.

Key clinical point: Long-term proactive management (PM) of psoriasis with calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) vs reactive management (RM) benefitted all patients irrespective of baseline characteristics, with greater benefits observed in patients with more severe disease.

Major finding: Effect of treatment on time to first relapse was consistent across all baseline parameters, with treatment group (PM vs RM; hazard ratio [HR], 0.56; P less than .001), baseline Physician Global Assessment (severe vs mild; HR, 2.32; P = .003), and modified Psoriasis Area Severity Index (severe vs mild; HR, 1.77; P = .002) having a significant impact.

Study details: This was a post hoc analysis of phase 3 PSO LONG trial which included a 52-week maintenance phase where patients with psoriasis were randomly assigned to Cal/BD twice weekly (PM) or vehicle foam (RM).

Disclosures: This study was supported by LEO Pharma, Ballerup, Denmark. MG Lebwohl, KA Papp, and RB Warren declared receiving research funds, honoraria for advisory board, speaker, and/or consultant services from various sources including LEO Pharma. MH Mørch and MYJ Bernasconi declared being employees of LEO Pharma.

Source: Lebwohl MG et al. Dermatol Ther (Heidelb). 2021 Aug 2. doi: 10.1007/s13555-021-00585-x.

Key clinical point: Long-term proactive management (PM) of psoriasis with calcipotriene 0.005%/betamethasone dipropionate 0.064% (Cal/BD) vs reactive management (RM) benefitted all patients irrespective of baseline characteristics, with greater benefits observed in patients with more severe disease.

Major finding: Effect of treatment on time to first relapse was consistent across all baseline parameters, with treatment group (PM vs RM; hazard ratio [HR], 0.56; P less than .001), baseline Physician Global Assessment (severe vs mild; HR, 2.32; P = .003), and modified Psoriasis Area Severity Index (severe vs mild; HR, 1.77; P = .002) having a significant impact.

Study details: This was a post hoc analysis of phase 3 PSO LONG trial which included a 52-week maintenance phase where patients with psoriasis were randomly assigned to Cal/BD twice weekly (PM) or vehicle foam (RM).

Disclosures: This study was supported by LEO Pharma, Ballerup, Denmark. MG Lebwohl, KA Papp, and RB Warren declared receiving research funds, honoraria for advisory board, speaker, and/or consultant services from various sources including LEO Pharma. MH Mørch and MYJ Bernasconi declared being employees of LEO Pharma.

Source: Lebwohl MG et al. Dermatol Ther (Heidelb). 2021 Aug 2. doi: 10.1007/s13555-021-00585-x.

Key clinical point: Dimethyl fumarate may be considered a first-line systemic treatment option to manage psoriasis in the elderly. However, long-term safety, particularly lymphocytopenia, should be closely monitored.

Major finding: The Psoriasis Area and Severity Index score ranged from 3.7 to -24.0 (mean, 9.8±4.1) at week 0, which changed to 4.3±3.2 at week 16 and 2.7±3.2 at week 24 after dimethyl fumarate administration. Overall, 72.8% of adverse events were reported, with the most common being gastrointestinal complaints (29.6%), flushes (12.3%), and lymphocytopenia (12.35%).

Study details: Findings are from a retrospective study including 81 elderly patients with moderate-to-severe psoriasis, aged 65 years and older, treated with dimethyl fumarate for up to 24 weeks.

Disclosures: No source of funding was declared. The authors declared no potential conflict of interests.

Source: Ricceri F et al. J Dermatolo Treat. 2021 Aug 11. doi: 10.1080/09546634.2021.1962000.

Key clinical point: Dimethyl fumarate may be considered a first-line systemic treatment option to manage psoriasis in the elderly. However, long-term safety, particularly lymphocytopenia, should be closely monitored.

Major finding: The Psoriasis Area and Severity Index score ranged from 3.7 to -24.0 (mean, 9.8±4.1) at week 0, which changed to 4.3±3.2 at week 16 and 2.7±3.2 at week 24 after dimethyl fumarate administration. Overall, 72.8% of adverse events were reported, with the most common being gastrointestinal complaints (29.6%), flushes (12.3%), and lymphocytopenia (12.35%).

Study details: Findings are from a retrospective study including 81 elderly patients with moderate-to-severe psoriasis, aged 65 years and older, treated with dimethyl fumarate for up to 24 weeks.

Disclosures: No source of funding was declared. The authors declared no potential conflict of interests.

Source: Ricceri F et al. J Dermatolo Treat. 2021 Aug 11. doi: 10.1080/09546634.2021.1962000.

Key clinical point: Dimethyl fumarate may be considered a first-line systemic treatment option to manage psoriasis in the elderly. However, long-term safety, particularly lymphocytopenia, should be closely monitored.

Major finding: The Psoriasis Area and Severity Index score ranged from 3.7 to -24.0 (mean, 9.8±4.1) at week 0, which changed to 4.3±3.2 at week 16 and 2.7±3.2 at week 24 after dimethyl fumarate administration. Overall, 72.8% of adverse events were reported, with the most common being gastrointestinal complaints (29.6%), flushes (12.3%), and lymphocytopenia (12.35%).

Study details: Findings are from a retrospective study including 81 elderly patients with moderate-to-severe psoriasis, aged 65 years and older, treated with dimethyl fumarate for up to 24 weeks.

Disclosures: No source of funding was declared. The authors declared no potential conflict of interests.

Source: Ricceri F et al. J Dermatolo Treat. 2021 Aug 11. doi: 10.1080/09546634.2021.1962000.

Key clinical point: Among patients with at least mild psoriasis, calcipotriol/betamethasone (Cal/BD) aerosol foam appeared to be beneficial with substantial itch relief and improvement in itch-related sleep loss, itch severity, and quality of life (QoL).

Major finding: The proportion of patients with itch and itch-related sleep loss reduced from 89.3% at baseline to 43.5% at week 4, and 93.4% of patients reported a 30% or more reduction in itch severity. The mean change in Dermatology Life Quality Index score at week 4 was −5.9±4.7, with 76.3% of patients achieving a score of 5 or lesser indicating no/small effect on QoL.

Study details: Findings are from CELSUS, a noninterventional prospective study including 400 patients with plaque psoriasis treated with Cal/BD aerosol foam.

Disclosures: This study was supported by LEO Pharma. Dr. Rigopoulos, Dr. Lazaridou, Dr. Georgiou, Dr. Chasapi, and Dr. Ioannides reported receiving personal fees from various sources including LEO Pharma, outside the submitted work.

Source: Rigopoulos D et al. J Eur Acad Dermatol Venereol. 2021 Aug 9. doi: 10.1111/jdv.17593.

Key clinical point: Among patients with at least mild psoriasis, calcipotriol/betamethasone (Cal/BD) aerosol foam appeared to be beneficial with substantial itch relief and improvement in itch-related sleep loss, itch severity, and quality of life (QoL).

Major finding: The proportion of patients with itch and itch-related sleep loss reduced from 89.3% at baseline to 43.5% at week 4, and 93.4% of patients reported a 30% or more reduction in itch severity. The mean change in Dermatology Life Quality Index score at week 4 was −5.9±4.7, with 76.3% of patients achieving a score of 5 or lesser indicating no/small effect on QoL.

Study details: Findings are from CELSUS, a noninterventional prospective study including 400 patients with plaque psoriasis treated with Cal/BD aerosol foam.

Disclosures: This study was supported by LEO Pharma. Dr. Rigopoulos, Dr. Lazaridou, Dr. Georgiou, Dr. Chasapi, and Dr. Ioannides reported receiving personal fees from various sources including LEO Pharma, outside the submitted work.

Source: Rigopoulos D et al. J Eur Acad Dermatol Venereol. 2021 Aug 9. doi: 10.1111/jdv.17593.

Key clinical point: Among patients with at least mild psoriasis, calcipotriol/betamethasone (Cal/BD) aerosol foam appeared to be beneficial with substantial itch relief and improvement in itch-related sleep loss, itch severity, and quality of life (QoL).

Major finding: The proportion of patients with itch and itch-related sleep loss reduced from 89.3% at baseline to 43.5% at week 4, and 93.4% of patients reported a 30% or more reduction in itch severity. The mean change in Dermatology Life Quality Index score at week 4 was −5.9±4.7, with 76.3% of patients achieving a score of 5 or lesser indicating no/small effect on QoL.

Study details: Findings are from CELSUS, a noninterventional prospective study including 400 patients with plaque psoriasis treated with Cal/BD aerosol foam.

Disclosures: This study was supported by LEO Pharma. Dr. Rigopoulos, Dr. Lazaridou, Dr. Georgiou, Dr. Chasapi, and Dr. Ioannides reported receiving personal fees from various sources including LEO Pharma, outside the submitted work.

Source: Rigopoulos D et al. J Eur Acad Dermatol Venereol. 2021 Aug 9. doi: 10.1111/jdv.17593.