Psoriasis

Use of tumor necrosis factor (TNF) inhibitors in patients with autoimmune diseases may increase risk for inflammatory central nervous system (CNS) outcomes, new research suggests

The nested case-control study included more than 200 participants with diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease. Results showed that exposure to TNF inhibitors was significantly associated with increased risk for demyelinating CNS events, such as multiple sclerosis, and nondemyelinating events, such as meningitis and encephalitis.

Interestingly, disease-specific secondary analyses showed that the strongest association for inflammatory events was in patients with rheumatoid arthritis.

Lead author Amy Kunchok, MD, of Mayo Clinic, Rochester, Minn., noted that “these are highly effective therapies for patients” and that these CNS events are likely uncommon.

“Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies in appropriate patients,” Dr. Kunchok said in an interview.

“Rather, we recommend that clinicians assessing patients with both inflammatory demyelinating and nondemyelinating CNS events consider a detailed evaluation of the medication history, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies,” she said.

The findings were published in JAMA Neurology.
 

Poorly understood

TNF inhibitors “are common therapies for certain autoimmune diseases,” the investigators noted.

Previously, a link between exposure to these inhibitors and inflammatory CNS events “has been postulated but is poorly understood,” they wrote.

In the current study, they examined records for 106 patients who were treated at Mayo clinics in Minnesota, Arizona, or Florida from January 2003 through February 2019. All participants had been diagnosed with an autoimmune disease that the Food and Drug Administration has listed as an indication for TNF inhibitor use. This included rheumatoid arthritis (n = 48), ankylosing spondylitis (n = 4), psoriasis and psoriatic arthritis (n = 21), Crohn’s disease (n = 27), and ulcerative colitis (n = 6). Their records also showed diagnostic codes for the inflammatory demyelinating CNS events of relapsing-remitting or primary progressive MS, clinically isolated syndrome, radiologically isolated syndrome, neuromyelitis optica spectrum disorder, and transverse myelitis or for the inflammatory nondemyelinating CNS events of meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis.  The investigators also included 106 age-, sex-, and autoimmune disease–matched participants 1:1 to act as the control group.

In the total study population, 64% were women and the median age at disease onset was 52 years. In addition, 60% of the patient group and 40% of the control group were exposed to TNF inhibitors.
 

Novel finding?

Results showed that TNF inhibitor exposure was significantly linked to increased risk for developing any inflammatory CNS event (adjusted odds ratio, 3.01; 95% CI, 1.55-5.82; P = .001). When the outcomes were stratified by class of inflammatory event, these results were similar. The aOR was 3.09 (95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and was 2.97 (95% CI, 1.15-7.65; P = .02) for inflammatory nondemyelinating events.

Dr. Kunchok noted that the association between the inhibitors and nondemyelinating events was “a novel finding from this study.”

In secondary analyses, patients with rheumatoid arthritis and exposure to TNF inhibitors had the strongest association with any inflammatory CNS event (aOR, 4.82; 95% CI, 1.62-14.36; P = .005).

A pooled cohort comprising only the participants with the other autoimmune diseases did not show a significant association between exposure to TNF inhibitors and development of CNS events (P = .09).

“Because of the lack of power, further stratification by individual autoimmune diseases was not analyzed,” the investigators reported.

Although the overall findings showed that exposure to TNF inhibitors was linked to increased risk for inflammatory events, whether this association “represents de novo or exacerbated inflammatory pathways requires further research,” the authors wrote.

Dr. Kunchok added that more research, especially population-based studies, is also needed to examine the incidence of these inflammatory CNS events in patients exposed to TNF-alpha inhibitors.
 

Adds to the literature

In an accompanying editorial, Jeffrey M. Gelfand, MD, department of neurology at the University of California, San Francisco, and Jinoos Yazdany, MD, Zuckerberg San Francisco General Hospital at UCSF, noted that although the study adds to the literature, the magnitude of the risk found “remains unclear.”

“Randomized clinical trials are not suited to the study of rare adverse events,” Dr. Gelfand and Dr. Yazdany wrote. They agree with Dr. Kunchok that “next steps should include population-based observational studies that control for disease severity.”

Still, the current study provides additional evidence of rare adverse events in patients receiving TNF inhibitors, they noted. So how should prescribers proceed?

“As with all treatments, the risk-benefit ratio for the individual patient’s situation must be weighed and appropriate counseling must be given to facilitate shared decision-making discussions,” wrote the editorialists.

“Given what is known about the risk of harm, avoiding TNF inhibitors is advisable in patients with known MS,” they wrote.

In addition, neurologic consultation can be helpful for clarifying diagnoses and providing advice on monitoring strategies for TNF inhibitor treatment in those with possible MS or other demyelinating conditions, noted the editorialists.

“In patients who develop new concerning neurological symptoms while receiving TNF inhibitor treatment, timely evaluation is indicated, including consideration of neuroinflammatory, infectious, and neurological diagnoses that may be unrelated to treatment,” they added.

“Broader awareness of risks that studies such as this one by Kunchok et al provide can ... encourage timelier recognition of potential TNF inhibitor–associated neuroinflammatory events and may improve outcomes for patients,” Dr. Gelfand and Dr. Yazdany concluded.

The study was funded by a grant from the National Center for Advancing Translational Sciences. Dr. Kunchok reports having received research funding from Biogen outside this study. A full list of disclosures for the other study authors is in the original article. Dr. Gelfand reports having received g rants for a clinical trial from Genentech and consulting fees from Biogen, Alexion, Theranica, Impel Neuropharma, Advanced Clinical, Biohaven, and Satsuma. Dr. Yazdany reports having received grants from Pfizer and consulting fees from AstraZeneca and Eli Lilly outside the submitted work.
 

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

Use of tumor necrosis factor (TNF) inhibitors in patients with autoimmune diseases may increase risk for inflammatory central nervous system (CNS) outcomes, new research suggests

The nested case-control study included more than 200 participants with diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease. Results showed that exposure to TNF inhibitors was significantly associated with increased risk for demyelinating CNS events, such as multiple sclerosis, and nondemyelinating events, such as meningitis and encephalitis.

Interestingly, disease-specific secondary analyses showed that the strongest association for inflammatory events was in patients with rheumatoid arthritis.

Lead author Amy Kunchok, MD, of Mayo Clinic, Rochester, Minn., noted that “these are highly effective therapies for patients” and that these CNS events are likely uncommon.

“Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies in appropriate patients,” Dr. Kunchok said in an interview.

“Rather, we recommend that clinicians assessing patients with both inflammatory demyelinating and nondemyelinating CNS events consider a detailed evaluation of the medication history, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies,” she said.

The findings were published in JAMA Neurology.
 

Poorly understood

TNF inhibitors “are common therapies for certain autoimmune diseases,” the investigators noted.

Previously, a link between exposure to these inhibitors and inflammatory CNS events “has been postulated but is poorly understood,” they wrote.

In the current study, they examined records for 106 patients who were treated at Mayo clinics in Minnesota, Arizona, or Florida from January 2003 through February 2019. All participants had been diagnosed with an autoimmune disease that the Food and Drug Administration has listed as an indication for TNF inhibitor use. This included rheumatoid arthritis (n = 48), ankylosing spondylitis (n = 4), psoriasis and psoriatic arthritis (n = 21), Crohn’s disease (n = 27), and ulcerative colitis (n = 6). Their records also showed diagnostic codes for the inflammatory demyelinating CNS events of relapsing-remitting or primary progressive MS, clinically isolated syndrome, radiologically isolated syndrome, neuromyelitis optica spectrum disorder, and transverse myelitis or for the inflammatory nondemyelinating CNS events of meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis.  The investigators also included 106 age-, sex-, and autoimmune disease–matched participants 1:1 to act as the control group.

In the total study population, 64% were women and the median age at disease onset was 52 years. In addition, 60% of the patient group and 40% of the control group were exposed to TNF inhibitors.
 

Novel finding?

Results showed that TNF inhibitor exposure was significantly linked to increased risk for developing any inflammatory CNS event (adjusted odds ratio, 3.01; 95% CI, 1.55-5.82; P = .001). When the outcomes were stratified by class of inflammatory event, these results were similar. The aOR was 3.09 (95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and was 2.97 (95% CI, 1.15-7.65; P = .02) for inflammatory nondemyelinating events.

Dr. Kunchok noted that the association between the inhibitors and nondemyelinating events was “a novel finding from this study.”

In secondary analyses, patients with rheumatoid arthritis and exposure to TNF inhibitors had the strongest association with any inflammatory CNS event (aOR, 4.82; 95% CI, 1.62-14.36; P = .005).

A pooled cohort comprising only the participants with the other autoimmune diseases did not show a significant association between exposure to TNF inhibitors and development of CNS events (P = .09).

“Because of the lack of power, further stratification by individual autoimmune diseases was not analyzed,” the investigators reported.

Although the overall findings showed that exposure to TNF inhibitors was linked to increased risk for inflammatory events, whether this association “represents de novo or exacerbated inflammatory pathways requires further research,” the authors wrote.

Dr. Kunchok added that more research, especially population-based studies, is also needed to examine the incidence of these inflammatory CNS events in patients exposed to TNF-alpha inhibitors.
 

Adds to the literature

In an accompanying editorial, Jeffrey M. Gelfand, MD, department of neurology at the University of California, San Francisco, and Jinoos Yazdany, MD, Zuckerberg San Francisco General Hospital at UCSF, noted that although the study adds to the literature, the magnitude of the risk found “remains unclear.”

“Randomized clinical trials are not suited to the study of rare adverse events,” Dr. Gelfand and Dr. Yazdany wrote. They agree with Dr. Kunchok that “next steps should include population-based observational studies that control for disease severity.”

Still, the current study provides additional evidence of rare adverse events in patients receiving TNF inhibitors, they noted. So how should prescribers proceed?

“As with all treatments, the risk-benefit ratio for the individual patient’s situation must be weighed and appropriate counseling must be given to facilitate shared decision-making discussions,” wrote the editorialists.

“Given what is known about the risk of harm, avoiding TNF inhibitors is advisable in patients with known MS,” they wrote.

In addition, neurologic consultation can be helpful for clarifying diagnoses and providing advice on monitoring strategies for TNF inhibitor treatment in those with possible MS or other demyelinating conditions, noted the editorialists.

“In patients who develop new concerning neurological symptoms while receiving TNF inhibitor treatment, timely evaluation is indicated, including consideration of neuroinflammatory, infectious, and neurological diagnoses that may be unrelated to treatment,” they added.

“Broader awareness of risks that studies such as this one by Kunchok et al provide can ... encourage timelier recognition of potential TNF inhibitor–associated neuroinflammatory events and may improve outcomes for patients,” Dr. Gelfand and Dr. Yazdany concluded.

The study was funded by a grant from the National Center for Advancing Translational Sciences. Dr. Kunchok reports having received research funding from Biogen outside this study. A full list of disclosures for the other study authors is in the original article. Dr. Gelfand reports having received g rants for a clinical trial from Genentech and consulting fees from Biogen, Alexion, Theranica, Impel Neuropharma, Advanced Clinical, Biohaven, and Satsuma. Dr. Yazdany reports having received grants from Pfizer and consulting fees from AstraZeneca and Eli Lilly outside the submitted work.
 

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

Use of tumor necrosis factor (TNF) inhibitors in patients with autoimmune diseases may increase risk for inflammatory central nervous system (CNS) outcomes, new research suggests

The nested case-control study included more than 200 participants with diseases such as rheumatoid arthritis, psoriasis, and Crohn’s disease. Results showed that exposure to TNF inhibitors was significantly associated with increased risk for demyelinating CNS events, such as multiple sclerosis, and nondemyelinating events, such as meningitis and encephalitis.

Interestingly, disease-specific secondary analyses showed that the strongest association for inflammatory events was in patients with rheumatoid arthritis.

Lead author Amy Kunchok, MD, of Mayo Clinic, Rochester, Minn., noted that “these are highly effective therapies for patients” and that these CNS events are likely uncommon.

“Our study has observed an association, but this does not imply causality. Therefore, we are not cautioning against using these therapies in appropriate patients,” Dr. Kunchok said in an interview.

“Rather, we recommend that clinicians assessing patients with both inflammatory demyelinating and nondemyelinating CNS events consider a detailed evaluation of the medication history, particularly in patients with coexistent autoimmune diseases who may have a current or past history of biological therapies,” she said.

The findings were published in JAMA Neurology.
 

Poorly understood

TNF inhibitors “are common therapies for certain autoimmune diseases,” the investigators noted.

Previously, a link between exposure to these inhibitors and inflammatory CNS events “has been postulated but is poorly understood,” they wrote.

In the current study, they examined records for 106 patients who were treated at Mayo clinics in Minnesota, Arizona, or Florida from January 2003 through February 2019. All participants had been diagnosed with an autoimmune disease that the Food and Drug Administration has listed as an indication for TNF inhibitor use. This included rheumatoid arthritis (n = 48), ankylosing spondylitis (n = 4), psoriasis and psoriatic arthritis (n = 21), Crohn’s disease (n = 27), and ulcerative colitis (n = 6). Their records also showed diagnostic codes for the inflammatory demyelinating CNS events of relapsing-remitting or primary progressive MS, clinically isolated syndrome, radiologically isolated syndrome, neuromyelitis optica spectrum disorder, and transverse myelitis or for the inflammatory nondemyelinating CNS events of meningitis, meningoencephalitis, encephalitis, neurosarcoidosis, and CNS vasculitis.  The investigators also included 106 age-, sex-, and autoimmune disease–matched participants 1:1 to act as the control group.

In the total study population, 64% were women and the median age at disease onset was 52 years. In addition, 60% of the patient group and 40% of the control group were exposed to TNF inhibitors.
 

Novel finding?

Results showed that TNF inhibitor exposure was significantly linked to increased risk for developing any inflammatory CNS event (adjusted odds ratio, 3.01; 95% CI, 1.55-5.82; P = .001). When the outcomes were stratified by class of inflammatory event, these results were similar. The aOR was 3.09 (95% CI, 1.19-8.04; P = .02) for inflammatory demyelinating CNS events and was 2.97 (95% CI, 1.15-7.65; P = .02) for inflammatory nondemyelinating events.

Dr. Kunchok noted that the association between the inhibitors and nondemyelinating events was “a novel finding from this study.”

In secondary analyses, patients with rheumatoid arthritis and exposure to TNF inhibitors had the strongest association with any inflammatory CNS event (aOR, 4.82; 95% CI, 1.62-14.36; P = .005).

A pooled cohort comprising only the participants with the other autoimmune diseases did not show a significant association between exposure to TNF inhibitors and development of CNS events (P = .09).

“Because of the lack of power, further stratification by individual autoimmune diseases was not analyzed,” the investigators reported.

Although the overall findings showed that exposure to TNF inhibitors was linked to increased risk for inflammatory events, whether this association “represents de novo or exacerbated inflammatory pathways requires further research,” the authors wrote.

Dr. Kunchok added that more research, especially population-based studies, is also needed to examine the incidence of these inflammatory CNS events in patients exposed to TNF-alpha inhibitors.
 

Adds to the literature

In an accompanying editorial, Jeffrey M. Gelfand, MD, department of neurology at the University of California, San Francisco, and Jinoos Yazdany, MD, Zuckerberg San Francisco General Hospital at UCSF, noted that although the study adds to the literature, the magnitude of the risk found “remains unclear.”

“Randomized clinical trials are not suited to the study of rare adverse events,” Dr. Gelfand and Dr. Yazdany wrote. They agree with Dr. Kunchok that “next steps should include population-based observational studies that control for disease severity.”

Still, the current study provides additional evidence of rare adverse events in patients receiving TNF inhibitors, they noted. So how should prescribers proceed?

“As with all treatments, the risk-benefit ratio for the individual patient’s situation must be weighed and appropriate counseling must be given to facilitate shared decision-making discussions,” wrote the editorialists.

“Given what is known about the risk of harm, avoiding TNF inhibitors is advisable in patients with known MS,” they wrote.

In addition, neurologic consultation can be helpful for clarifying diagnoses and providing advice on monitoring strategies for TNF inhibitor treatment in those with possible MS or other demyelinating conditions, noted the editorialists.

“In patients who develop new concerning neurological symptoms while receiving TNF inhibitor treatment, timely evaluation is indicated, including consideration of neuroinflammatory, infectious, and neurological diagnoses that may be unrelated to treatment,” they added.

“Broader awareness of risks that studies such as this one by Kunchok et al provide can ... encourage timelier recognition of potential TNF inhibitor–associated neuroinflammatory events and may improve outcomes for patients,” Dr. Gelfand and Dr. Yazdany concluded.

The study was funded by a grant from the National Center for Advancing Translational Sciences. Dr. Kunchok reports having received research funding from Biogen outside this study. A full list of disclosures for the other study authors is in the original article. Dr. Gelfand reports having received g rants for a clinical trial from Genentech and consulting fees from Biogen, Alexion, Theranica, Impel Neuropharma, Advanced Clinical, Biohaven, and Satsuma. Dr. Yazdany reports having received grants from Pfizer and consulting fees from AstraZeneca and Eli Lilly outside the submitted work.
 

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

Humira outsold all other drugs in 2019 in terms of revenue as cytokine inhibitor medications earned their way to three of the first four spots on the pharmaceutical best-seller list, according to a new analysis from the IQVIA Institute for Human Data Science.

Sales of Humira (adalimumab) amounted to $21.4 billion before discounting, Murray Aitken, the institute’s executive director, and associates wrote in their analysis. That’s more than double the total of the anticoagulant Eliquis (apixaban), which brought in $9.9 billion in its last year before generic forms became available.

The next two spots were filled by the tumor necrosis factor inhibitor Enbrel (etanercept) with $8.1 billion in sales and the interleukin 12/23 inhibitor Stelara (ustekinumab) with sales totaling $6.6 billion, followed by the chemotherapy drug Keytruda (pembrolizumab) close behind after racking up $6.5 billion in sales, the researchers reported.

Total nondiscounted spending on all drugs in the U.S. market came to $511 billion in 2019, an increase of 5.7% over the $484 billion spent in 2018, based on data from the July 2020 IQVIA National Sales Perspectives.

These figures are “not adjusted for estimates of off-invoice discounts and rebates,” the authors noted, but they include “prescription and insulin products sold into chain and independent pharmacies, food store pharmacies, mail service pharmacies, long-term care facilities, hospitals, clinics, and other institutional settings.”

Those “discounts and rebates” do exist, however, and they can add up. Drug sales for 2019, “after deducting negotiated rebates, discounts, and other forms of price concessions, such as patient coupons or vouchers that offset out-of-pocket costs,” were $235 billion less than overall nondiscounted spending, the report noted.

Now that we’ve shown you the money, let’s take a quick look at volume. The leading drugs by number of dispensed prescriptions in 2019 were, not surprisingly, quite different. First, with 118 million prescriptions, was atorvastatin, followed by levothyroxine (113 million), lisinopril (96), amlodipine (89), and metoprolol (85), Mr. Aitken and associates reported.

Altogether, over 4.2 billion prescriptions were dispensed last year, with a couple of caveats: 90-day and 30-day fills were both counted as one prescription, and OTC drugs were not included, they pointed out.

[email protected]

Humira outsold all other drugs in 2019 in terms of revenue as cytokine inhibitor medications earned their way to three of the first four spots on the pharmaceutical best-seller list, according to a new analysis from the IQVIA Institute for Human Data Science.

Sales of Humira (adalimumab) amounted to $21.4 billion before discounting, Murray Aitken, the institute’s executive director, and associates wrote in their analysis. That’s more than double the total of the anticoagulant Eliquis (apixaban), which brought in $9.9 billion in its last year before generic forms became available.

The next two spots were filled by the tumor necrosis factor inhibitor Enbrel (etanercept) with $8.1 billion in sales and the interleukin 12/23 inhibitor Stelara (ustekinumab) with sales totaling $6.6 billion, followed by the chemotherapy drug Keytruda (pembrolizumab) close behind after racking up $6.5 billion in sales, the researchers reported.

Total nondiscounted spending on all drugs in the U.S. market came to $511 billion in 2019, an increase of 5.7% over the $484 billion spent in 2018, based on data from the July 2020 IQVIA National Sales Perspectives.

These figures are “not adjusted for estimates of off-invoice discounts and rebates,” the authors noted, but they include “prescription and insulin products sold into chain and independent pharmacies, food store pharmacies, mail service pharmacies, long-term care facilities, hospitals, clinics, and other institutional settings.”

Those “discounts and rebates” do exist, however, and they can add up. Drug sales for 2019, “after deducting negotiated rebates, discounts, and other forms of price concessions, such as patient coupons or vouchers that offset out-of-pocket costs,” were $235 billion less than overall nondiscounted spending, the report noted.

Now that we’ve shown you the money, let’s take a quick look at volume. The leading drugs by number of dispensed prescriptions in 2019 were, not surprisingly, quite different. First, with 118 million prescriptions, was atorvastatin, followed by levothyroxine (113 million), lisinopril (96), amlodipine (89), and metoprolol (85), Mr. Aitken and associates reported.

Altogether, over 4.2 billion prescriptions were dispensed last year, with a couple of caveats: 90-day and 30-day fills were both counted as one prescription, and OTC drugs were not included, they pointed out.

[email protected]

Humira outsold all other drugs in 2019 in terms of revenue as cytokine inhibitor medications earned their way to three of the first four spots on the pharmaceutical best-seller list, according to a new analysis from the IQVIA Institute for Human Data Science.

Sales of Humira (adalimumab) amounted to $21.4 billion before discounting, Murray Aitken, the institute’s executive director, and associates wrote in their analysis. That’s more than double the total of the anticoagulant Eliquis (apixaban), which brought in $9.9 billion in its last year before generic forms became available.

The next two spots were filled by the tumor necrosis factor inhibitor Enbrel (etanercept) with $8.1 billion in sales and the interleukin 12/23 inhibitor Stelara (ustekinumab) with sales totaling $6.6 billion, followed by the chemotherapy drug Keytruda (pembrolizumab) close behind after racking up $6.5 billion in sales, the researchers reported.

Total nondiscounted spending on all drugs in the U.S. market came to $511 billion in 2019, an increase of 5.7% over the $484 billion spent in 2018, based on data from the July 2020 IQVIA National Sales Perspectives.

These figures are “not adjusted for estimates of off-invoice discounts and rebates,” the authors noted, but they include “prescription and insulin products sold into chain and independent pharmacies, food store pharmacies, mail service pharmacies, long-term care facilities, hospitals, clinics, and other institutional settings.”

Those “discounts and rebates” do exist, however, and they can add up. Drug sales for 2019, “after deducting negotiated rebates, discounts, and other forms of price concessions, such as patient coupons or vouchers that offset out-of-pocket costs,” were $235 billion less than overall nondiscounted spending, the report noted.

Now that we’ve shown you the money, let’s take a quick look at volume. The leading drugs by number of dispensed prescriptions in 2019 were, not surprisingly, quite different. First, with 118 million prescriptions, was atorvastatin, followed by levothyroxine (113 million), lisinopril (96), amlodipine (89), and metoprolol (85), Mr. Aitken and associates reported.

Altogether, over 4.2 billion prescriptions were dispensed last year, with a couple of caveats: 90-day and 30-day fills were both counted as one prescription, and OTC drugs were not included, they pointed out.

[email protected]

Psoriasis is a systemic immune-mediated disorder characterized by erythematous, scaly, well-demarcated plaques on the skin that affects approximately 3% of the world’s population.¹ Although topical therapies often are the first-line treatment of mild to moderate psoriasis, approximately 1 in 6 individuals has moderate to severe disease that requires systemic treatment such as biologics or phototherapy.² In patients with localized disease that is refractory to treatment or who have moderate to severe psoriasis requiring systemic treatment, phototherapy should be considered as a potential low-risk treatment option.

In July 2019, the American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) released an updated set of guidelines for the use of phototherapy in treating adult patients with psoriasis.³ Since the prior guidelines were released in 2010, there have been numerous studies affirming the efficacy of phototherapy, with several large meta-analyses helping to refine clinical recommendations.^4,5 Each treatment was ranked using Strength of Recommendation Taxonomy, with a score of A, B, or C based on the strength of the evidence supporting the given modality. With the ever-increasing number of treatment options for patients with psoriasis, these guidelines inform dermatologists of the recommendations for the initiation, maintenance, and optimization of phototherapy in the treatment of psoriasis.

The AAD-NPF recommendations discuss the mechanism of action, efficacy, safety, and frequency of adverse events of 10 commonly used phototherapy/photochemotherapy modalities. They also address dosing regimens, the potential to combine phototherapy with other therapies, and the efficacy of treatment modalities for different types of psoriasis.³ The purpose of this discussion is to present these guidelines in a condensed form for prescribers of phototherapy and to review the most clinically significant considerations during each step of treatment. Of note, we only highlight the treatment of adult patients and do not discuss information relevant to pediatric patients with psoriasis.

Choosing a Phototherapy Modality

Phototherapy may be considered for patients with psoriasis that affects more than 3% body surface area or for localized disease refractory to conventional treatments. UV light is believed to provide relief from psoriasis via multiple mechanisms, such as through favorable alterations in cytokine profiles, initiation of apoptosis, and local immunosupression.⁶ There is no single first-line phototherapeutic modality recommended for all patients with psoriasis. Rather, the decision to implement a particular modality should be individualized to the patient, considering factors such as percentage of body surface area affected by disease, quality-of-life assessment, comorbidities, lifestyle, and cost of treatment.

Of the 10 phototherapy modalities reviewed in these guidelines, 4 were ranked by the AAD and NPF as having grade A evidence for efficacy in the treatment of moderate to severe plaque psoriasis. Treatments with a grade A level of recommendation included narrowband UVB (NB-UVB), broadband UVB (BB-UVB), targeted phototherapy (excimer laser and excimer lamp), and oral psoralen plus UVA (PUVA) therapy. Photodynamic therapy for psoriasis was given an A-level recommendation against its use, as it was found to be ineffective with an unfavorable side-effect profile. Treatments with a grade B level of recommendation—nonoral routes of PUVA therapy, pulsed dye laser/intense pulsed light for nail psoriasis only, Goeckerman therapy, and climatotherapy—have sufficient evidence available to support their treatment of moderate to severe psoriasis in some cases. Treatments with a grade C level of recommendation—Grenz ray therapy (also called borderline or ultrasoft therapy) and visible light therapy—have insufficient evidence to support their use in patients with moderate to severe psoriasis (Table 1).

Psoralen plus UVA, which may be used topically (ie, bathwater PUVA) or taken orally, refers to treatment with photosensitizing psoralens. Psoralens are agents that intercalate with DNA and enhance the efficacy of phototherapy.¹⁰ Topical PUVA, with a grade B level of recommendation, is an effective treatment option for patients with localized disease and has been shown to be particularly efficacious in the treatment of palmoplantar pustular psoriasis. Oral PUVA is an effective option for psoriasis with a grade A recommendation, while bathwater PUVA has a grade B level of recommendation for moderate to severe plaque psoriasis. Oral PUVA is associated with greater systemic side effects (both acute and subacute) compared with NB-UVB and also is associated with photocarcinogenesis, particularly squamous cell carcinoma in white patients.¹¹ Other side effects from PUVA include pigmented macules in sun-protected areas (known as PUVA lentigines), which may make evaluation of skin lesions challenging. Because of the increased risk for cancer with oral PUVA, NB-UVB is preferable as a first-line treatment vs PUVA, especially in patients with a history of skin cancer.^12,13

Goeckerman therapy, which involves the synergistic combination of UVB and crude coal tar, is an older treatment that has shown efficacy in the treatment of severe or recalcitrant psoriasis (grade B level of recommendation). One prior case-control study comparing the efficacy of Goeckerman therapy with newer treatments, such as biologic therapies, steroids, and oral immunosuppressants, found a similar reduction in symptoms among both treatment groups, with longer disease-free periods in patients who received Goeckerman therapy than those who received newer therapies (22.3 years vs 4.6 months).¹⁴ However, Goeckerman therapy is utilized less frequently than more modern therapies because of the time required for treatment and declining insurance reimbursements for it. Climatotherapy, another older established therapy, involves the temporary or permanent relocation of patients to an environment that is favorable for disease control (grade B level of recommendation). Locations such as the Dead Sea and Canary Islands have been studied and shown to provide both subjective and objective improvement in patients’ psoriasis disease course. Patients had notable improvement in both their psoriasis area and severity index score and quality of life after a 3- to 4-week relocation to these areas.^15,16 Access to climatotherapy and the transient nature of disease relief are apparent limitations of this treatment modality.

Grenz ray is a type of phototherapy that uses longer-wavelength ionizing radiation, which has low penetrance into surrounding tissues and a 95% absorption rate within the first 3 mm of the skin depth. This treatment has been used less frequently since the development of newer alternatives but should still be considered as a second line to UV therapy, especially in cases of recalcitrant disease and palmoplantar psoriasis, and when access to other treatment options is limited. Grenz ray has a grade C level of recommendation due to the paucity of evidence that supports its efficacy. Thus, it is not recommended as first-line therapy for the treatment of moderate to severe psoriasis. Visible light therapy is another treatment option that uses light in the visible wavelength spectrum but predominantly utilizes blue and red light. Psoriatic lesions are sensitive to light therapy because of the elevated levels of naturally occurring photosensitizing agents, called protoporphyrins, in these lesions.¹⁷ Several small studies have shown improvement in psoriatic lesions treated with visible light therapy, with blue light showing greater efficacy in lesional clearance than red light.^18,19

Pulsed dye laser is a phototherapy modality that has shown efficacy in the treatment of nail psoriasis (grade B level of recommendation). One study comparing the effects of tazarotene cream 0.1% with pulsed dye laser and tazarotene cream 0.1% alone showed that patients receiving combination therapy had a greater decrease in nail psoriasis severity index scores, higher scores on the patient’s global assessment of improvement, and higher rates of improvement on the physician global assessment score. A physician global assessment score of 75% improvement or more was seen in patients treated with combination therapy vs monotherapy (5.3% vs 31.6%).²⁰ Intense pulsed light, a type of visible light therapy, also has been used to treat nail psoriasis, with one study showing notable improvement in nail bed and matrix disease and a global improvement in nail psoriasis severity index score after 6 months of biweekly treatment.²¹ However, this treatment has a grade B level of recommendation given the limited number of studies supporting the efficacy of this modality.

Initiation of Phototherapy

Prior to initiating phototherapy, it is important to assess the patient for any personal or family history of skin cancer, as phototherapy carries an increased risk for cutaneous malignancy, especially in patients with a history of skin cancer.^22,23 All patients also should be evaluated for their Fitzpatrick skin type, and the minimal erythema dose should be defined for those initiating UVB treatment. These classifications can be useful for the initial determination of treatment dose and the prevention of treatment-related adverse events (TRAEs). A careful drug history also should be taken before the initiation of phototherapy to avoid photosensitizing reactions. Thiazide diuretics and tetracyclines are 2 such examples of medications commonly associated with photosensitizing reactions.²⁴

Fitzpatrick skin type and/or minimal erythema dose testing also are essential in determining the appropriate initial NB-UVB dose required for treatment initiation (Table 2). Patient response to the initial NB-UVB trial will determine the optimal dosage for subsequent maintenance treatments.

Assessment and Optimization of Phototherapy

After an appropriate starting dosage has been established, patients should be evaluated at each subsequent visit for the degree of treatment response. Excessive erythema (lasting more than 48 hours) or adverse effects, such as itching, stinging, or burning, are indications that the patient should have their dose adjusted back to the last dose without such adverse responses. Because tolerance to treatment develops over time, patients who miss a scheduled dose of NB-UVB phototherapy require their dose to be temporarily lowered. Targeted dosage of UVB phototherapy at a frequency of 2 to 3 times weekly is preferred over treatment 1 to 2 times weekly; however, consideration should be given toward patient preference.²⁶ Dosing may be increased at a rate of 5% to 10% after each treatment, as tolerated, if there is no clearance of skin lesions with the original treatment dose. Patient skin type also is helpful in dictating the maximum phototherapy dose for each patient (Table 3).

Once a patient’s psoriatic lesions have cleared, the patient has the option to taper or indefinitely continue maintenance therapy. The established protocol for patients who choose to taper therapy is treatment twice weekly for 4 weeks, followed by once-weekly treatment for the second month. The maintenance dosage is held constant during the taper. For patients who prefer indefinite maintenance therapy, treatment is administered every 1 to 2 weeks, with a maintenance dosage that is approximately 25% lower than the original maintenance dosage.

Treatment Considerations

Efforts should be made to ensure that the long-term sequalae of phototherapy are minimized (Table 1). Development of cataracts is a recognized consequence of prolonged UVB exposure; therefore, eye protection is recommended during all UVB treatment sessions to reduce the risk for ocular toxicity. Although pregnancy is not a contraindication to phototherapy, except for PUVA, there is a dose-dependent degradation of folate with NB-UVB treatment, so folate supplementation (0.8 mg) is recommended during NB-UVB treatment to prevent development of neural tube defects in fetuses of patients who are pregnant or who may become pregnant.²⁷

Although phototherapy carries the theoretical risk for photocarcinogenesis, multiple studies have shown no increased risk for malignancy with either NB-UVB or BB-UVB phototherapy.^22,23 Regardless, patients who develop new-onset skin cancer while receiving any phototherapeutic treatment should discuss the potential risks and benefits of continued treatment with their physician. Providers should take extra caution prior to initiating treatment, especially in patients with a history of cutaneous malignancy. Because oral PUVA is a systemic therapy, it is associated with a greater risk for photocarcinogenesis than any other modality, particularly in fair-skinned individuals. Patients younger than 10 years; pregnant or nursing patients; and those with a history of lupus, xeroderma pigmentosum, or melanoma should not receive PUVA therapy because of their increased risk for photocarcinogenesis and TRAEs.

The decision to switch patients between different phototherapy modalities during treatment should be individualized to each patient based on factors such as disease severity, quality of life, and treatment burden. Other factors to consider include dosing frequency, treatment cost, and logistical factors, such as proximity to a treatment facility. Physicians should have a detailed discussion about the risks and benefits of continuing therapy for patients who develop new-onset skin cancer during phototherapy.

Final Thoughts

Phototherapy is an effective and safe treatment for patients with psoriasis who have localized and systemic disease. There are several treatment modalities that can be tailored to patient needs and preferences, such as home NB-UVB for patients who are unable or unwilling to undergo office-based treatments. Phototherapy has few absolute contraindications; however, relative contraindications to phototherapy exist. Patients with a history of skin cancer, photosensitivity disorders, and autoimmune diseases (eg, lupus) carry greater risks for adverse events, such as sun-related damage, cancer, and dysplasia. Because these conditions may preclude patients from pursuing phototherapy as a safe and effective approach to treating moderate to severe psoriasis, these patients should be considered for other therapies, such as biologic medications, which may carry a more favorable risk-benefit ratio given that individual’s background.

Psoriasis is a systemic immune-mediated disorder characterized by erythematous, scaly, well-demarcated plaques on the skin that affects approximately 3% of the world’s population.¹ Although topical therapies often are the first-line treatment of mild to moderate psoriasis, approximately 1 in 6 individuals has moderate to severe disease that requires systemic treatment such as biologics or phototherapy.² In patients with localized disease that is refractory to treatment or who have moderate to severe psoriasis requiring systemic treatment, phototherapy should be considered as a potential low-risk treatment option.

In July 2019, the American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) released an updated set of guidelines for the use of phototherapy in treating adult patients with psoriasis.³ Since the prior guidelines were released in 2010, there have been numerous studies affirming the efficacy of phototherapy, with several large meta-analyses helping to refine clinical recommendations.^4,5 Each treatment was ranked using Strength of Recommendation Taxonomy, with a score of A, B, or C based on the strength of the evidence supporting the given modality. With the ever-increasing number of treatment options for patients with psoriasis, these guidelines inform dermatologists of the recommendations for the initiation, maintenance, and optimization of phototherapy in the treatment of psoriasis.

The AAD-NPF recommendations discuss the mechanism of action, efficacy, safety, and frequency of adverse events of 10 commonly used phototherapy/photochemotherapy modalities. They also address dosing regimens, the potential to combine phototherapy with other therapies, and the efficacy of treatment modalities for different types of psoriasis.³ The purpose of this discussion is to present these guidelines in a condensed form for prescribers of phototherapy and to review the most clinically significant considerations during each step of treatment. Of note, we only highlight the treatment of adult patients and do not discuss information relevant to pediatric patients with psoriasis.

Choosing a Phototherapy Modality

Phototherapy may be considered for patients with psoriasis that affects more than 3% body surface area or for localized disease refractory to conventional treatments. UV light is believed to provide relief from psoriasis via multiple mechanisms, such as through favorable alterations in cytokine profiles, initiation of apoptosis, and local immunosupression.⁶ There is no single first-line phototherapeutic modality recommended for all patients with psoriasis. Rather, the decision to implement a particular modality should be individualized to the patient, considering factors such as percentage of body surface area affected by disease, quality-of-life assessment, comorbidities, lifestyle, and cost of treatment.

Of the 10 phototherapy modalities reviewed in these guidelines, 4 were ranked by the AAD and NPF as having grade A evidence for efficacy in the treatment of moderate to severe plaque psoriasis. Treatments with a grade A level of recommendation included narrowband UVB (NB-UVB), broadband UVB (BB-UVB), targeted phototherapy (excimer laser and excimer lamp), and oral psoralen plus UVA (PUVA) therapy. Photodynamic therapy for psoriasis was given an A-level recommendation against its use, as it was found to be ineffective with an unfavorable side-effect profile. Treatments with a grade B level of recommendation—nonoral routes of PUVA therapy, pulsed dye laser/intense pulsed light for nail psoriasis only, Goeckerman therapy, and climatotherapy—have sufficient evidence available to support their treatment of moderate to severe psoriasis in some cases. Treatments with a grade C level of recommendation—Grenz ray therapy (also called borderline or ultrasoft therapy) and visible light therapy—have insufficient evidence to support their use in patients with moderate to severe psoriasis (Table 1).

Psoralen plus UVA, which may be used topically (ie, bathwater PUVA) or taken orally, refers to treatment with photosensitizing psoralens. Psoralens are agents that intercalate with DNA and enhance the efficacy of phototherapy.¹⁰ Topical PUVA, with a grade B level of recommendation, is an effective treatment option for patients with localized disease and has been shown to be particularly efficacious in the treatment of palmoplantar pustular psoriasis. Oral PUVA is an effective option for psoriasis with a grade A recommendation, while bathwater PUVA has a grade B level of recommendation for moderate to severe plaque psoriasis. Oral PUVA is associated with greater systemic side effects (both acute and subacute) compared with NB-UVB and also is associated with photocarcinogenesis, particularly squamous cell carcinoma in white patients.¹¹ Other side effects from PUVA include pigmented macules in sun-protected areas (known as PUVA lentigines), which may make evaluation of skin lesions challenging. Because of the increased risk for cancer with oral PUVA, NB-UVB is preferable as a first-line treatment vs PUVA, especially in patients with a history of skin cancer.^12,13

Goeckerman therapy, which involves the synergistic combination of UVB and crude coal tar, is an older treatment that has shown efficacy in the treatment of severe or recalcitrant psoriasis (grade B level of recommendation). One prior case-control study comparing the efficacy of Goeckerman therapy with newer treatments, such as biologic therapies, steroids, and oral immunosuppressants, found a similar reduction in symptoms among both treatment groups, with longer disease-free periods in patients who received Goeckerman therapy than those who received newer therapies (22.3 years vs 4.6 months).¹⁴ However, Goeckerman therapy is utilized less frequently than more modern therapies because of the time required for treatment and declining insurance reimbursements for it. Climatotherapy, another older established therapy, involves the temporary or permanent relocation of patients to an environment that is favorable for disease control (grade B level of recommendation). Locations such as the Dead Sea and Canary Islands have been studied and shown to provide both subjective and objective improvement in patients’ psoriasis disease course. Patients had notable improvement in both their psoriasis area and severity index score and quality of life after a 3- to 4-week relocation to these areas.^15,16 Access to climatotherapy and the transient nature of disease relief are apparent limitations of this treatment modality.

Grenz ray is a type of phototherapy that uses longer-wavelength ionizing radiation, which has low penetrance into surrounding tissues and a 95% absorption rate within the first 3 mm of the skin depth. This treatment has been used less frequently since the development of newer alternatives but should still be considered as a second line to UV therapy, especially in cases of recalcitrant disease and palmoplantar psoriasis, and when access to other treatment options is limited. Grenz ray has a grade C level of recommendation due to the paucity of evidence that supports its efficacy. Thus, it is not recommended as first-line therapy for the treatment of moderate to severe psoriasis. Visible light therapy is another treatment option that uses light in the visible wavelength spectrum but predominantly utilizes blue and red light. Psoriatic lesions are sensitive to light therapy because of the elevated levels of naturally occurring photosensitizing agents, called protoporphyrins, in these lesions.¹⁷ Several small studies have shown improvement in psoriatic lesions treated with visible light therapy, with blue light showing greater efficacy in lesional clearance than red light.^18,19

Pulsed dye laser is a phototherapy modality that has shown efficacy in the treatment of nail psoriasis (grade B level of recommendation). One study comparing the effects of tazarotene cream 0.1% with pulsed dye laser and tazarotene cream 0.1% alone showed that patients receiving combination therapy had a greater decrease in nail psoriasis severity index scores, higher scores on the patient’s global assessment of improvement, and higher rates of improvement on the physician global assessment score. A physician global assessment score of 75% improvement or more was seen in patients treated with combination therapy vs monotherapy (5.3% vs 31.6%).²⁰ Intense pulsed light, a type of visible light therapy, also has been used to treat nail psoriasis, with one study showing notable improvement in nail bed and matrix disease and a global improvement in nail psoriasis severity index score after 6 months of biweekly treatment.²¹ However, this treatment has a grade B level of recommendation given the limited number of studies supporting the efficacy of this modality.

Initiation of Phototherapy

Prior to initiating phototherapy, it is important to assess the patient for any personal or family history of skin cancer, as phototherapy carries an increased risk for cutaneous malignancy, especially in patients with a history of skin cancer.^22,23 All patients also should be evaluated for their Fitzpatrick skin type, and the minimal erythema dose should be defined for those initiating UVB treatment. These classifications can be useful for the initial determination of treatment dose and the prevention of treatment-related adverse events (TRAEs). A careful drug history also should be taken before the initiation of phototherapy to avoid photosensitizing reactions. Thiazide diuretics and tetracyclines are 2 such examples of medications commonly associated with photosensitizing reactions.²⁴

Fitzpatrick skin type and/or minimal erythema dose testing also are essential in determining the appropriate initial NB-UVB dose required for treatment initiation (Table 2). Patient response to the initial NB-UVB trial will determine the optimal dosage for subsequent maintenance treatments.

Assessment and Optimization of Phototherapy

After an appropriate starting dosage has been established, patients should be evaluated at each subsequent visit for the degree of treatment response. Excessive erythema (lasting more than 48 hours) or adverse effects, such as itching, stinging, or burning, are indications that the patient should have their dose adjusted back to the last dose without such adverse responses. Because tolerance to treatment develops over time, patients who miss a scheduled dose of NB-UVB phototherapy require their dose to be temporarily lowered. Targeted dosage of UVB phototherapy at a frequency of 2 to 3 times weekly is preferred over treatment 1 to 2 times weekly; however, consideration should be given toward patient preference.²⁶ Dosing may be increased at a rate of 5% to 10% after each treatment, as tolerated, if there is no clearance of skin lesions with the original treatment dose. Patient skin type also is helpful in dictating the maximum phototherapy dose for each patient (Table 3).

Once a patient’s psoriatic lesions have cleared, the patient has the option to taper or indefinitely continue maintenance therapy. The established protocol for patients who choose to taper therapy is treatment twice weekly for 4 weeks, followed by once-weekly treatment for the second month. The maintenance dosage is held constant during the taper. For patients who prefer indefinite maintenance therapy, treatment is administered every 1 to 2 weeks, with a maintenance dosage that is approximately 25% lower than the original maintenance dosage.

Treatment Considerations

Efforts should be made to ensure that the long-term sequalae of phototherapy are minimized (Table 1). Development of cataracts is a recognized consequence of prolonged UVB exposure; therefore, eye protection is recommended during all UVB treatment sessions to reduce the risk for ocular toxicity. Although pregnancy is not a contraindication to phototherapy, except for PUVA, there is a dose-dependent degradation of folate with NB-UVB treatment, so folate supplementation (0.8 mg) is recommended during NB-UVB treatment to prevent development of neural tube defects in fetuses of patients who are pregnant or who may become pregnant.²⁷

Although phototherapy carries the theoretical risk for photocarcinogenesis, multiple studies have shown no increased risk for malignancy with either NB-UVB or BB-UVB phototherapy.^22,23 Regardless, patients who develop new-onset skin cancer while receiving any phototherapeutic treatment should discuss the potential risks and benefits of continued treatment with their physician. Providers should take extra caution prior to initiating treatment, especially in patients with a history of cutaneous malignancy. Because oral PUVA is a systemic therapy, it is associated with a greater risk for photocarcinogenesis than any other modality, particularly in fair-skinned individuals. Patients younger than 10 years; pregnant or nursing patients; and those with a history of lupus, xeroderma pigmentosum, or melanoma should not receive PUVA therapy because of their increased risk for photocarcinogenesis and TRAEs.

The decision to switch patients between different phototherapy modalities during treatment should be individualized to each patient based on factors such as disease severity, quality of life, and treatment burden. Other factors to consider include dosing frequency, treatment cost, and logistical factors, such as proximity to a treatment facility. Physicians should have a detailed discussion about the risks and benefits of continuing therapy for patients who develop new-onset skin cancer during phototherapy.

Final Thoughts

Phototherapy is an effective and safe treatment for patients with psoriasis who have localized and systemic disease. There are several treatment modalities that can be tailored to patient needs and preferences, such as home NB-UVB for patients who are unable or unwilling to undergo office-based treatments. Phototherapy has few absolute contraindications; however, relative contraindications to phototherapy exist. Patients with a history of skin cancer, photosensitivity disorders, and autoimmune diseases (eg, lupus) carry greater risks for adverse events, such as sun-related damage, cancer, and dysplasia. Because these conditions may preclude patients from pursuing phototherapy as a safe and effective approach to treating moderate to severe psoriasis, these patients should be considered for other therapies, such as biologic medications, which may carry a more favorable risk-benefit ratio given that individual’s background.

Psoriasis is a systemic immune-mediated disorder characterized by erythematous, scaly, well-demarcated plaques on the skin that affects approximately 3% of the world’s population.¹ Although topical therapies often are the first-line treatment of mild to moderate psoriasis, approximately 1 in 6 individuals has moderate to severe disease that requires systemic treatment such as biologics or phototherapy.² In patients with localized disease that is refractory to treatment or who have moderate to severe psoriasis requiring systemic treatment, phototherapy should be considered as a potential low-risk treatment option.

In July 2019, the American Academy of Dermatology (AAD) and National Psoriasis Foundation (NPF) released an updated set of guidelines for the use of phototherapy in treating adult patients with psoriasis.³ Since the prior guidelines were released in 2010, there have been numerous studies affirming the efficacy of phototherapy, with several large meta-analyses helping to refine clinical recommendations.^4,5 Each treatment was ranked using Strength of Recommendation Taxonomy, with a score of A, B, or C based on the strength of the evidence supporting the given modality. With the ever-increasing number of treatment options for patients with psoriasis, these guidelines inform dermatologists of the recommendations for the initiation, maintenance, and optimization of phototherapy in the treatment of psoriasis.

The AAD-NPF recommendations discuss the mechanism of action, efficacy, safety, and frequency of adverse events of 10 commonly used phototherapy/photochemotherapy modalities. They also address dosing regimens, the potential to combine phototherapy with other therapies, and the efficacy of treatment modalities for different types of psoriasis.³ The purpose of this discussion is to present these guidelines in a condensed form for prescribers of phototherapy and to review the most clinically significant considerations during each step of treatment. Of note, we only highlight the treatment of adult patients and do not discuss information relevant to pediatric patients with psoriasis.

Choosing a Phototherapy Modality

Phototherapy may be considered for patients with psoriasis that affects more than 3% body surface area or for localized disease refractory to conventional treatments. UV light is believed to provide relief from psoriasis via multiple mechanisms, such as through favorable alterations in cytokine profiles, initiation of apoptosis, and local immunosupression.⁶ There is no single first-line phototherapeutic modality recommended for all patients with psoriasis. Rather, the decision to implement a particular modality should be individualized to the patient, considering factors such as percentage of body surface area affected by disease, quality-of-life assessment, comorbidities, lifestyle, and cost of treatment.

Of the 10 phototherapy modalities reviewed in these guidelines, 4 were ranked by the AAD and NPF as having grade A evidence for efficacy in the treatment of moderate to severe plaque psoriasis. Treatments with a grade A level of recommendation included narrowband UVB (NB-UVB), broadband UVB (BB-UVB), targeted phototherapy (excimer laser and excimer lamp), and oral psoralen plus UVA (PUVA) therapy. Photodynamic therapy for psoriasis was given an A-level recommendation against its use, as it was found to be ineffective with an unfavorable side-effect profile. Treatments with a grade B level of recommendation—nonoral routes of PUVA therapy, pulsed dye laser/intense pulsed light for nail psoriasis only, Goeckerman therapy, and climatotherapy—have sufficient evidence available to support their treatment of moderate to severe psoriasis in some cases. Treatments with a grade C level of recommendation—Grenz ray therapy (also called borderline or ultrasoft therapy) and visible light therapy—have insufficient evidence to support their use in patients with moderate to severe psoriasis (Table 1).

Psoralen plus UVA, which may be used topically (ie, bathwater PUVA) or taken orally, refers to treatment with photosensitizing psoralens. Psoralens are agents that intercalate with DNA and enhance the efficacy of phototherapy.¹⁰ Topical PUVA, with a grade B level of recommendation, is an effective treatment option for patients with localized disease and has been shown to be particularly efficacious in the treatment of palmoplantar pustular psoriasis. Oral PUVA is an effective option for psoriasis with a grade A recommendation, while bathwater PUVA has a grade B level of recommendation for moderate to severe plaque psoriasis. Oral PUVA is associated with greater systemic side effects (both acute and subacute) compared with NB-UVB and also is associated with photocarcinogenesis, particularly squamous cell carcinoma in white patients.¹¹ Other side effects from PUVA include pigmented macules in sun-protected areas (known as PUVA lentigines), which may make evaluation of skin lesions challenging. Because of the increased risk for cancer with oral PUVA, NB-UVB is preferable as a first-line treatment vs PUVA, especially in patients with a history of skin cancer.^12,13

Goeckerman therapy, which involves the synergistic combination of UVB and crude coal tar, is an older treatment that has shown efficacy in the treatment of severe or recalcitrant psoriasis (grade B level of recommendation). One prior case-control study comparing the efficacy of Goeckerman therapy with newer treatments, such as biologic therapies, steroids, and oral immunosuppressants, found a similar reduction in symptoms among both treatment groups, with longer disease-free periods in patients who received Goeckerman therapy than those who received newer therapies (22.3 years vs 4.6 months).¹⁴ However, Goeckerman therapy is utilized less frequently than more modern therapies because of the time required for treatment and declining insurance reimbursements for it. Climatotherapy, another older established therapy, involves the temporary or permanent relocation of patients to an environment that is favorable for disease control (grade B level of recommendation). Locations such as the Dead Sea and Canary Islands have been studied and shown to provide both subjective and objective improvement in patients’ psoriasis disease course. Patients had notable improvement in both their psoriasis area and severity index score and quality of life after a 3- to 4-week relocation to these areas.^15,16 Access to climatotherapy and the transient nature of disease relief are apparent limitations of this treatment modality.

Grenz ray is a type of phototherapy that uses longer-wavelength ionizing radiation, which has low penetrance into surrounding tissues and a 95% absorption rate within the first 3 mm of the skin depth. This treatment has been used less frequently since the development of newer alternatives but should still be considered as a second line to UV therapy, especially in cases of recalcitrant disease and palmoplantar psoriasis, and when access to other treatment options is limited. Grenz ray has a grade C level of recommendation due to the paucity of evidence that supports its efficacy. Thus, it is not recommended as first-line therapy for the treatment of moderate to severe psoriasis. Visible light therapy is another treatment option that uses light in the visible wavelength spectrum but predominantly utilizes blue and red light. Psoriatic lesions are sensitive to light therapy because of the elevated levels of naturally occurring photosensitizing agents, called protoporphyrins, in these lesions.¹⁷ Several small studies have shown improvement in psoriatic lesions treated with visible light therapy, with blue light showing greater efficacy in lesional clearance than red light.^18,19

Pulsed dye laser is a phototherapy modality that has shown efficacy in the treatment of nail psoriasis (grade B level of recommendation). One study comparing the effects of tazarotene cream 0.1% with pulsed dye laser and tazarotene cream 0.1% alone showed that patients receiving combination therapy had a greater decrease in nail psoriasis severity index scores, higher scores on the patient’s global assessment of improvement, and higher rates of improvement on the physician global assessment score. A physician global assessment score of 75% improvement or more was seen in patients treated with combination therapy vs monotherapy (5.3% vs 31.6%).²⁰ Intense pulsed light, a type of visible light therapy, also has been used to treat nail psoriasis, with one study showing notable improvement in nail bed and matrix disease and a global improvement in nail psoriasis severity index score after 6 months of biweekly treatment.²¹ However, this treatment has a grade B level of recommendation given the limited number of studies supporting the efficacy of this modality.

Initiation of Phototherapy

Prior to initiating phototherapy, it is important to assess the patient for any personal or family history of skin cancer, as phototherapy carries an increased risk for cutaneous malignancy, especially in patients with a history of skin cancer.^22,23 All patients also should be evaluated for their Fitzpatrick skin type, and the minimal erythema dose should be defined for those initiating UVB treatment. These classifications can be useful for the initial determination of treatment dose and the prevention of treatment-related adverse events (TRAEs). A careful drug history also should be taken before the initiation of phototherapy to avoid photosensitizing reactions. Thiazide diuretics and tetracyclines are 2 such examples of medications commonly associated with photosensitizing reactions.²⁴

Fitzpatrick skin type and/or minimal erythema dose testing also are essential in determining the appropriate initial NB-UVB dose required for treatment initiation (Table 2). Patient response to the initial NB-UVB trial will determine the optimal dosage for subsequent maintenance treatments.

Assessment and Optimization of Phototherapy

After an appropriate starting dosage has been established, patients should be evaluated at each subsequent visit for the degree of treatment response. Excessive erythema (lasting more than 48 hours) or adverse effects, such as itching, stinging, or burning, are indications that the patient should have their dose adjusted back to the last dose without such adverse responses. Because tolerance to treatment develops over time, patients who miss a scheduled dose of NB-UVB phototherapy require their dose to be temporarily lowered. Targeted dosage of UVB phototherapy at a frequency of 2 to 3 times weekly is preferred over treatment 1 to 2 times weekly; however, consideration should be given toward patient preference.²⁶ Dosing may be increased at a rate of 5% to 10% after each treatment, as tolerated, if there is no clearance of skin lesions with the original treatment dose. Patient skin type also is helpful in dictating the maximum phototherapy dose for each patient (Table 3).

Once a patient’s psoriatic lesions have cleared, the patient has the option to taper or indefinitely continue maintenance therapy. The established protocol for patients who choose to taper therapy is treatment twice weekly for 4 weeks, followed by once-weekly treatment for the second month. The maintenance dosage is held constant during the taper. For patients who prefer indefinite maintenance therapy, treatment is administered every 1 to 2 weeks, with a maintenance dosage that is approximately 25% lower than the original maintenance dosage.

Treatment Considerations

Efforts should be made to ensure that the long-term sequalae of phototherapy are minimized (Table 1). Development of cataracts is a recognized consequence of prolonged UVB exposure; therefore, eye protection is recommended during all UVB treatment sessions to reduce the risk for ocular toxicity. Although pregnancy is not a contraindication to phototherapy, except for PUVA, there is a dose-dependent degradation of folate with NB-UVB treatment, so folate supplementation (0.8 mg) is recommended during NB-UVB treatment to prevent development of neural tube defects in fetuses of patients who are pregnant or who may become pregnant.²⁷

Although phototherapy carries the theoretical risk for photocarcinogenesis, multiple studies have shown no increased risk for malignancy with either NB-UVB or BB-UVB phototherapy.^22,23 Regardless, patients who develop new-onset skin cancer while receiving any phototherapeutic treatment should discuss the potential risks and benefits of continued treatment with their physician. Providers should take extra caution prior to initiating treatment, especially in patients with a history of cutaneous malignancy. Because oral PUVA is a systemic therapy, it is associated with a greater risk for photocarcinogenesis than any other modality, particularly in fair-skinned individuals. Patients younger than 10 years; pregnant or nursing patients; and those with a history of lupus, xeroderma pigmentosum, or melanoma should not receive PUVA therapy because of their increased risk for photocarcinogenesis and TRAEs.

The decision to switch patients between different phototherapy modalities during treatment should be individualized to each patient based on factors such as disease severity, quality of life, and treatment burden. Other factors to consider include dosing frequency, treatment cost, and logistical factors, such as proximity to a treatment facility. Physicians should have a detailed discussion about the risks and benefits of continuing therapy for patients who develop new-onset skin cancer during phototherapy.

Final Thoughts

Phototherapy is an effective and safe treatment for patients with psoriasis who have localized and systemic disease. There are several treatment modalities that can be tailored to patient needs and preferences, such as home NB-UVB for patients who are unable or unwilling to undergo office-based treatments. Phototherapy has few absolute contraindications; however, relative contraindications to phototherapy exist. Patients with a history of skin cancer, photosensitivity disorders, and autoimmune diseases (eg, lupus) carry greater risks for adverse events, such as sun-related damage, cancer, and dysplasia. Because these conditions may preclude patients from pursuing phototherapy as a safe and effective approach to treating moderate to severe psoriasis, these patients should be considered for other therapies, such as biologic medications, which may carry a more favorable risk-benefit ratio given that individual’s background.

To the Editor:

Psoriasis is a chronic inflammatory papulosquamous skin disease affecting 2% to 3% of the population.¹ Its pathogenesis is multifactorial, consisting of a disrupted skin barrier and dysregulated immune activation.²

A wide armamentarium of topical and systemic treatments targeting different aspects of the disease pathogenesis have been developed over the years.^3,4 Psoriasis was once considered a skin disease exclusively, but accumulating evidence suggests that it is accompanied by a multitude of systemic inflammatory comorbidities.⁵ This insight supports the concept of systemic treatment for patients with moderate to severe psoriasis. As a chronic disease, psoriasis requires continuous therapy. The treatment approach should focus on achieving efficacy and minimizing side effects. These goals can be achieved by combination, rotational, and sequential treatment approaches.⁶ Many therapeutic combinations have proven effective, using beneficially different mechanisms of action (MOAs) and toxicity profiles.⁷ We present a patient with moderate to severe recalcitrant palmoplantar psoriasis who demonstrated improvement with combination therapy.

A 50-year-old man presented with palmoplantar psoriasis of 7 years’ duration. His medical history included mild hyperlipidemia treated with atorvastatin. Prior topical treatments including calcipotriene, betamethasone dipropionate, and tacrolimus ointment did not result in improvement. Persistent acral involvement required further intervention, and the excimer laser was added to the therapeutic regimen with a minor additive therapeutic value. Acitretin (25 mg/d) was initiated; however, the disease flared up soon after. Acitretin was discontinued, and the patient was treated with apremilast (30 mg twice daily) for 9 months with a slight improvement. Physical examination revealed erythematous, fissured, scaly plaques involving both the palms and soles. Acitretin (25 mg/d) was reintroduced to the therapeutic regimen, and the acitretin-apremilast combination was used for 2 months. With this regimen, the patient experienced 90% improvement (Figures 1 and 2).

Acitretin, the active metabolite of etretinate, modulates epidermal differentiation and has immunomodulating activities.¹⁷ It commonly is used for treating palmoplantar psoriasis.⁸ Until recently, it was the only nonimmunosuppressive systemic treatment for psoriasis, and its combination with other systemic treatments, particularly biologics, has been advocated.¹⁸ Prior reports showed remarkable disease improvement when combining acitretin with alefacept, etanercept, infliximab, adalimumab, and ustekinumab.¹⁹ The optimal combination should include modalities with different MOAs without overlapping toxicities.¹⁹ Apremilast and acitretin have different MOAs and side-effect profiles, but another theoretical advantage is that they both interfere with intracellular signaling on the transcription level rather than affecting extracellular targets.¹³

Our patient with moderate to severe recalcitrant palmoplantar psoriasis demonstrated approximately 90% improvement following apremilast and acitretin combination therapy. This treatment regimen should be considered in cases of persistent acral disease resistant to other therapeutic efforts.

To the Editor:

Psoriasis is a chronic inflammatory papulosquamous skin disease affecting 2% to 3% of the population.¹ Its pathogenesis is multifactorial, consisting of a disrupted skin barrier and dysregulated immune activation.²

A wide armamentarium of topical and systemic treatments targeting different aspects of the disease pathogenesis have been developed over the years.^3,4 Psoriasis was once considered a skin disease exclusively, but accumulating evidence suggests that it is accompanied by a multitude of systemic inflammatory comorbidities.⁵ This insight supports the concept of systemic treatment for patients with moderate to severe psoriasis. As a chronic disease, psoriasis requires continuous therapy. The treatment approach should focus on achieving efficacy and minimizing side effects. These goals can be achieved by combination, rotational, and sequential treatment approaches.⁶ Many therapeutic combinations have proven effective, using beneficially different mechanisms of action (MOAs) and toxicity profiles.⁷ We present a patient with moderate to severe recalcitrant palmoplantar psoriasis who demonstrated improvement with combination therapy.

A 50-year-old man presented with palmoplantar psoriasis of 7 years’ duration. His medical history included mild hyperlipidemia treated with atorvastatin. Prior topical treatments including calcipotriene, betamethasone dipropionate, and tacrolimus ointment did not result in improvement. Persistent acral involvement required further intervention, and the excimer laser was added to the therapeutic regimen with a minor additive therapeutic value. Acitretin (25 mg/d) was initiated; however, the disease flared up soon after. Acitretin was discontinued, and the patient was treated with apremilast (30 mg twice daily) for 9 months with a slight improvement. Physical examination revealed erythematous, fissured, scaly plaques involving both the palms and soles. Acitretin (25 mg/d) was reintroduced to the therapeutic regimen, and the acitretin-apremilast combination was used for 2 months. With this regimen, the patient experienced 90% improvement (Figures 1 and 2).

Acitretin, the active metabolite of etretinate, modulates epidermal differentiation and has immunomodulating activities.¹⁷ It commonly is used for treating palmoplantar psoriasis.⁸ Until recently, it was the only nonimmunosuppressive systemic treatment for psoriasis, and its combination with other systemic treatments, particularly biologics, has been advocated.¹⁸ Prior reports showed remarkable disease improvement when combining acitretin with alefacept, etanercept, infliximab, adalimumab, and ustekinumab.¹⁹ The optimal combination should include modalities with different MOAs without overlapping toxicities.¹⁹ Apremilast and acitretin have different MOAs and side-effect profiles, but another theoretical advantage is that they both interfere with intracellular signaling on the transcription level rather than affecting extracellular targets.¹³

Our patient with moderate to severe recalcitrant palmoplantar psoriasis demonstrated approximately 90% improvement following apremilast and acitretin combination therapy. This treatment regimen should be considered in cases of persistent acral disease resistant to other therapeutic efforts.

To the Editor:

Psoriasis is a chronic inflammatory papulosquamous skin disease affecting 2% to 3% of the population.¹ Its pathogenesis is multifactorial, consisting of a disrupted skin barrier and dysregulated immune activation.²

A wide armamentarium of topical and systemic treatments targeting different aspects of the disease pathogenesis have been developed over the years.^3,4 Psoriasis was once considered a skin disease exclusively, but accumulating evidence suggests that it is accompanied by a multitude of systemic inflammatory comorbidities.⁵ This insight supports the concept of systemic treatment for patients with moderate to severe psoriasis. As a chronic disease, psoriasis requires continuous therapy. The treatment approach should focus on achieving efficacy and minimizing side effects. These goals can be achieved by combination, rotational, and sequential treatment approaches.⁶ Many therapeutic combinations have proven effective, using beneficially different mechanisms of action (MOAs) and toxicity profiles.⁷ We present a patient with moderate to severe recalcitrant palmoplantar psoriasis who demonstrated improvement with combination therapy.

A 50-year-old man presented with palmoplantar psoriasis of 7 years’ duration. His medical history included mild hyperlipidemia treated with atorvastatin. Prior topical treatments including calcipotriene, betamethasone dipropionate, and tacrolimus ointment did not result in improvement. Persistent acral involvement required further intervention, and the excimer laser was added to the therapeutic regimen with a minor additive therapeutic value. Acitretin (25 mg/d) was initiated; however, the disease flared up soon after. Acitretin was discontinued, and the patient was treated with apremilast (30 mg twice daily) for 9 months with a slight improvement. Physical examination revealed erythematous, fissured, scaly plaques involving both the palms and soles. Acitretin (25 mg/d) was reintroduced to the therapeutic regimen, and the acitretin-apremilast combination was used for 2 months. With this regimen, the patient experienced 90% improvement (Figures 1 and 2).

Acitretin, the active metabolite of etretinate, modulates epidermal differentiation and has immunomodulating activities.¹⁷ It commonly is used for treating palmoplantar psoriasis.⁸ Until recently, it was the only nonimmunosuppressive systemic treatment for psoriasis, and its combination with other systemic treatments, particularly biologics, has been advocated.¹⁸ Prior reports showed remarkable disease improvement when combining acitretin with alefacept, etanercept, infliximab, adalimumab, and ustekinumab.¹⁹ The optimal combination should include modalities with different MOAs without overlapping toxicities.¹⁹ Apremilast and acitretin have different MOAs and side-effect profiles, but another theoretical advantage is that they both interfere with intracellular signaling on the transcription level rather than affecting extracellular targets.¹³

Our patient with moderate to severe recalcitrant palmoplantar psoriasis demonstrated approximately 90% improvement following apremilast and acitretin combination therapy. This treatment regimen should be considered in cases of persistent acral disease resistant to other therapeutic efforts.

All PASI 100 responses to psoriasis therapy are not the same, Andrew Blauvelt, MD, declared at the virtual annual meeting of the American Academy of Dermatology.

He presented a first-of-its-kind study that potentially opens the door to a new, more rigorous standard for treatment success in psoriasis: Not simply cleared lesional skin as captured by a Psoriasis Area and Severity Index (PASI) 100 response, but also clearance of residual psoriasis signs and symptoms – as well as what he termed “molecular clearance.”

“We’ve found that clearing skin with drugs utilizing different mechanisms of action may lead to differential consequences for our patients,” observed Dr. Blauvelt, a dermatologist and clinical trialist who is president of the Oregon Medical Research Center, Portland.

A PASI 100 response, traditionally considered an elusive goal for the great majority of patients with severe psoriasis, can now often be achieved using today’s top-tier, high-performance biologics. But Dr. Blauvelt and his coinvestigators are interested in pushing even beyond PASI 100 to a new frontier of therapeutic benefit.

He presented a secondary analysis of the previously reported VOYAGE 1 and 2 head-to-head randomized trials of guselkumab (Tremfya) versus adalimumab (Humira) for treatment of moderate to severe psoriasis. This new analysis, which focused exclusively on PASI 100 responders by week 24, demonstrated that patients with a PASI 100 response to guselkumab, an interleukin (IL)-23 inhibitor, had significantly fewer persistent symptoms and signs of psoriasis than those whose skin clearance was attained using adalimumab, a tumor necrosis factor (TNF) inhibitor.

Moreover, the investigators showed that the gene expression profile of PASI 100 responders who were free of signs and symptoms was more normalized than that of patients with residual symptoms despite their cleared skin.

The analysis included 16 participants in the VOYAGE trials who achieved PASI 100 at week 24 on guselkumab and 5 who did so on adalimumab. At baseline and again at week 24, these individuals completed the Psoriasis Symptoms and Signs Diary (PSSD). Also, biopsies of lesional and nonlesional skin were obtained at baseline and of cleared lesional skin at week 24 for transcriptomic microarray analysis of the expression of many thousands of genes.
 

Persistent psoriasis symptoms despite cleared skin

The PSSD involves patient ratings of various psoriasis symptoms and signs. Total scores can range from 0 (symptom- and sign-free) up to 100. At week 24, a significantly higher proportion of guselkumab-treated PASI 100 responders had a total PSSD score of zero: 55%, versus 43% in the adalimumab group. This was consistently true across the board for each of the individual signs and symptoms assessed. For example, 61% of the guselkumab group gave themselves a zero for itch, as did 50% of the adalimumab group. Sixty-four percent on guselkumab and 52% on adalimumab reported being free of redness. And 78% of the guselkumab group reported being pain-free, compared with 69% with adalimumab, Dr. Blauvelt reported.

Gene expression analysis

At baseline, more than 2,300 dysregulated genes were identified in lesional skin while functioning normally in nonlesional skin. The great majority of these initially dysregulated genes became normalized in cleared lesional skin in PASI 100 responders at week 24. However, 25 of the genes remained dysregulated in cleared lesional skin, meaning they displayed less than 75% of normal function. Ten of these 25 genes with dysregulated expression at follow-up showed abnormal function in patients with residual symptoms despite cleared skin, but they functioned normally in those without persistent symptoms. This raises the possibility that the residual symptoms of psoriasis were attributable to the abnormal gene functioning, according to Dr. Blauvelt.

Of note, 9 of the 10 dysregulated genes in cleared lesional skin of patients with residual symptoms were present in the adalimumab group; these included two genes localized to the epidermal differentiation complex as well as the psoriasis-specific proline-rich 9 gene known as PRR9, which is induced by IL-17A. In contrast, only four genes, none of which were localized to the epidermal differentiation complex, were insufficiently normalized in the cleared lesional skin of guselkumab-treated PASI-100 responders.

“Nothing like this analysis has ever been done before,” the dermatologist observed. “It’s a pilot study. Perhaps with more data like this, we’ll be using this type of information in clinical practice to go beyond clearing patients’ skin.”

Dr. Blauvelt reported serving as a scientific advisor to and paid clinical investigator for Janssen, which sponsored the study, as well as for roughly two dozen other pharmaceutical companies.

[email protected]

All PASI 100 responses to psoriasis therapy are not the same, Andrew Blauvelt, MD, declared at the virtual annual meeting of the American Academy of Dermatology.

He presented a first-of-its-kind study that potentially opens the door to a new, more rigorous standard for treatment success in psoriasis: Not simply cleared lesional skin as captured by a Psoriasis Area and Severity Index (PASI) 100 response, but also clearance of residual psoriasis signs and symptoms – as well as what he termed “molecular clearance.”

“We’ve found that clearing skin with drugs utilizing different mechanisms of action may lead to differential consequences for our patients,” observed Dr. Blauvelt, a dermatologist and clinical trialist who is president of the Oregon Medical Research Center, Portland.

A PASI 100 response, traditionally considered an elusive goal for the great majority of patients with severe psoriasis, can now often be achieved using today’s top-tier, high-performance biologics. But Dr. Blauvelt and his coinvestigators are interested in pushing even beyond PASI 100 to a new frontier of therapeutic benefit.

He presented a secondary analysis of the previously reported VOYAGE 1 and 2 head-to-head randomized trials of guselkumab (Tremfya) versus adalimumab (Humira) for treatment of moderate to severe psoriasis. This new analysis, which focused exclusively on PASI 100 responders by week 24, demonstrated that patients with a PASI 100 response to guselkumab, an interleukin (IL)-23 inhibitor, had significantly fewer persistent symptoms and signs of psoriasis than those whose skin clearance was attained using adalimumab, a tumor necrosis factor (TNF) inhibitor.

Moreover, the investigators showed that the gene expression profile of PASI 100 responders who were free of signs and symptoms was more normalized than that of patients with residual symptoms despite their cleared skin.

The analysis included 16 participants in the VOYAGE trials who achieved PASI 100 at week 24 on guselkumab and 5 who did so on adalimumab. At baseline and again at week 24, these individuals completed the Psoriasis Symptoms and Signs Diary (PSSD). Also, biopsies of lesional and nonlesional skin were obtained at baseline and of cleared lesional skin at week 24 for transcriptomic microarray analysis of the expression of many thousands of genes.
 

Persistent psoriasis symptoms despite cleared skin

The PSSD involves patient ratings of various psoriasis symptoms and signs. Total scores can range from 0 (symptom- and sign-free) up to 100. At week 24, a significantly higher proportion of guselkumab-treated PASI 100 responders had a total PSSD score of zero: 55%, versus 43% in the adalimumab group. This was consistently true across the board for each of the individual signs and symptoms assessed. For example, 61% of the guselkumab group gave themselves a zero for itch, as did 50% of the adalimumab group. Sixty-four percent on guselkumab and 52% on adalimumab reported being free of redness. And 78% of the guselkumab group reported being pain-free, compared with 69% with adalimumab, Dr. Blauvelt reported.

Gene expression analysis

At baseline, more than 2,300 dysregulated genes were identified in lesional skin while functioning normally in nonlesional skin. The great majority of these initially dysregulated genes became normalized in cleared lesional skin in PASI 100 responders at week 24. However, 25 of the genes remained dysregulated in cleared lesional skin, meaning they displayed less than 75% of normal function. Ten of these 25 genes with dysregulated expression at follow-up showed abnormal function in patients with residual symptoms despite cleared skin, but they functioned normally in those without persistent symptoms. This raises the possibility that the residual symptoms of psoriasis were attributable to the abnormal gene functioning, according to Dr. Blauvelt.

Of note, 9 of the 10 dysregulated genes in cleared lesional skin of patients with residual symptoms were present in the adalimumab group; these included two genes localized to the epidermal differentiation complex as well as the psoriasis-specific proline-rich 9 gene known as PRR9, which is induced by IL-17A. In contrast, only four genes, none of which were localized to the epidermal differentiation complex, were insufficiently normalized in the cleared lesional skin of guselkumab-treated PASI-100 responders.

“Nothing like this analysis has ever been done before,” the dermatologist observed. “It’s a pilot study. Perhaps with more data like this, we’ll be using this type of information in clinical practice to go beyond clearing patients’ skin.”

Dr. Blauvelt reported serving as a scientific advisor to and paid clinical investigator for Janssen, which sponsored the study, as well as for roughly two dozen other pharmaceutical companies.

[email protected]

All PASI 100 responses to psoriasis therapy are not the same, Andrew Blauvelt, MD, declared at the virtual annual meeting of the American Academy of Dermatology.

He presented a first-of-its-kind study that potentially opens the door to a new, more rigorous standard for treatment success in psoriasis: Not simply cleared lesional skin as captured by a Psoriasis Area and Severity Index (PASI) 100 response, but also clearance of residual psoriasis signs and symptoms – as well as what he termed “molecular clearance.”

“We’ve found that clearing skin with drugs utilizing different mechanisms of action may lead to differential consequences for our patients,” observed Dr. Blauvelt, a dermatologist and clinical trialist who is president of the Oregon Medical Research Center, Portland.

A PASI 100 response, traditionally considered an elusive goal for the great majority of patients with severe psoriasis, can now often be achieved using today’s top-tier, high-performance biologics. But Dr. Blauvelt and his coinvestigators are interested in pushing even beyond PASI 100 to a new frontier of therapeutic benefit.

He presented a secondary analysis of the previously reported VOYAGE 1 and 2 head-to-head randomized trials of guselkumab (Tremfya) versus adalimumab (Humira) for treatment of moderate to severe psoriasis. This new analysis, which focused exclusively on PASI 100 responders by week 24, demonstrated that patients with a PASI 100 response to guselkumab, an interleukin (IL)-23 inhibitor, had significantly fewer persistent symptoms and signs of psoriasis than those whose skin clearance was attained using adalimumab, a tumor necrosis factor (TNF) inhibitor.

Moreover, the investigators showed that the gene expression profile of PASI 100 responders who were free of signs and symptoms was more normalized than that of patients with residual symptoms despite their cleared skin.

The analysis included 16 participants in the VOYAGE trials who achieved PASI 100 at week 24 on guselkumab and 5 who did so on adalimumab. At baseline and again at week 24, these individuals completed the Psoriasis Symptoms and Signs Diary (PSSD). Also, biopsies of lesional and nonlesional skin were obtained at baseline and of cleared lesional skin at week 24 for transcriptomic microarray analysis of the expression of many thousands of genes.
 

Persistent psoriasis symptoms despite cleared skin

The PSSD involves patient ratings of various psoriasis symptoms and signs. Total scores can range from 0 (symptom- and sign-free) up to 100. At week 24, a significantly higher proportion of guselkumab-treated PASI 100 responders had a total PSSD score of zero: 55%, versus 43% in the adalimumab group. This was consistently true across the board for each of the individual signs and symptoms assessed. For example, 61% of the guselkumab group gave themselves a zero for itch, as did 50% of the adalimumab group. Sixty-four percent on guselkumab and 52% on adalimumab reported being free of redness. And 78% of the guselkumab group reported being pain-free, compared with 69% with adalimumab, Dr. Blauvelt reported.

Gene expression analysis

At baseline, more than 2,300 dysregulated genes were identified in lesional skin while functioning normally in nonlesional skin. The great majority of these initially dysregulated genes became normalized in cleared lesional skin in PASI 100 responders at week 24. However, 25 of the genes remained dysregulated in cleared lesional skin, meaning they displayed less than 75% of normal function. Ten of these 25 genes with dysregulated expression at follow-up showed abnormal function in patients with residual symptoms despite cleared skin, but they functioned normally in those without persistent symptoms. This raises the possibility that the residual symptoms of psoriasis were attributable to the abnormal gene functioning, according to Dr. Blauvelt.

Of note, 9 of the 10 dysregulated genes in cleared lesional skin of patients with residual symptoms were present in the adalimumab group; these included two genes localized to the epidermal differentiation complex as well as the psoriasis-specific proline-rich 9 gene known as PRR9, which is induced by IL-17A. In contrast, only four genes, none of which were localized to the epidermal differentiation complex, were insufficiently normalized in the cleared lesional skin of guselkumab-treated PASI-100 responders.

“Nothing like this analysis has ever been done before,” the dermatologist observed. “It’s a pilot study. Perhaps with more data like this, we’ll be using this type of information in clinical practice to go beyond clearing patients’ skin.”

Dr. Blauvelt reported serving as a scientific advisor to and paid clinical investigator for Janssen, which sponsored the study, as well as for roughly two dozen other pharmaceutical companies.

[email protected]

Collecting cells from the skin surface with adhesive tape strips is demonstrating a level of accuracy that is rivaling skin biopsies for atopic dermatitis and psoriasis, promising a minimally invasive approach for monitoring these and potentially other dermatologic diseases, according to the latest advances with this approach.

Courtesy Mount Sinai Health System

“Tape strips are not going to fully replace biopsies, but we think they will have an important role in diagnosing and monitoring response to therapy by avoiding the potential scarring and pain of biopsy,” reported Emma Guttman-Yassky, MD, PhD, professor of dermatology and director of the laboratory inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai Medical Center, New York.

The concept of using adhesive strips to remove surface skin cells for clinical study has been around for more than 20 years, but there has been recent progress. A newly published study, which compared skin from patients with atopic dermatitis (AD) or psoriasis with that of controls, was characterized as “the most comprehensive tape strip molecular profiling in any inflammatory skin disease to date and the first to fully characterize and compare AD to psoriasis,” wrote Dr. Guttman-Yassky, the senior author, and coauthors.

It also appears to be a leap forward. RNA sequencing detected thousands of differentially expressed genes reflecting immune and barrier biomarkers characteristic of the molecular phenotypes of atopic dermatitis and psoriasis. These were not only found to be consistent with biopsy studies but identified additional unique genes and pathways relevant to their pathological signature.

“In the past, the success rate for transcriptome sequencing even for a more limited panel of proteins was approaching 50% when considering both lesional, nonlesional skin, and healthy skin, but we are now approaching 100% for sample recovery and for analysis of RNA and genes,” Dr. Guttman-Yassky said in an interview.

Tissue samples were obtained with tape strips from lesional and nonlesional skin from 20 patients with AD and 20 patients with psoriasis. Compared with 20 tape strips from controls, they were evaluated with RNA sequencing followed by quantitative real-time polymerase chain reaction of immune and barrier biomarkers.

The sample recovery rate was 96% overall and 95% or better regardless of whether the skin was lesional or nonlesional.

With RNA sequencing of more than 20,000 transcripts, including multiple cellular, immune, and barrier biomarkers, an enormous amount of data was generated, but the key finding is that these diseases are readily distinguished with profiling based on tape strips.

Although numerous biomarkers were shared, “tape strips completely discriminate between atopic dermatitis and psoriasis with a degree of reliability that is comparable to skin biopsy,” Dr. Guttman-Yassky said.

One of the biomarkers, expression of nitric oxide synthase 2/inducible nitric oxide synthase, distinguished AD from psoriasis with 100% accuracy. As previously reported in biopsy studies, other biomarkers collectively associated AD with a profile related to a Th2-type inflammatory response and psoriasis with a Th17-type inflammatory response.

Tape strips also confirmed significant pathology in the nonlesional as well as the lesional skin of patients with AD or psoriasis. This included an increase in Th2-type products, such as interleukin-4 and IL-13, in nonlesional skin of atopic dermatitis and Th17-type products, such as IL-17, in nonlesional skin of psoriasis.

Some biomarkers of AD and psoriasis had an even greater differentiation in tape strips than previously reported from biopsy studies, according to Dr. Guttman-Yassky. In this study, tape strips also captured more differentially expressed genes than previously reported with biopsies.

One potential limitation of tape strips is that the RNA isolation process is time consuming, but this might be less of an issue in routine clinical use if there is a more refined number of biomarkers that are targeted or if technological improvements simplify processing, Dr. Guttman-Yassky pointed out.

To develop clinical utility for tape strips beyond AD and psoriasis, more work is needed to standardize the depth of sampling, which is variable with tape strips, she noted. Depth is relevant to the analysis of gene expression and mRNA activity of each dermatologic disease.

“Tape strips remain a research tool for now, but we do think that this technique can be refined and employed for clinical purposes, including diagnosis and monitoring response to treatment,” she said.

Relative to biopsy, the advantages are not difficult to envision. Dr. Guttman-Yassky, who recently published a study of tape strips for evaluating AD in children emphasized that tape strips are generally painless.

“Patients really do not mind tape strips,” she said. Although she believes that tape strips are providing unique insight into the pathology of inflammatory diseases not necessarily available with biopsy, she emphasized the practical value. Not least, “these could really help when the goal is to evaluate response to therapy over time.”

Another investigator who has conducted studies with tape strips, Maja-Lisa Clausen, MD, PhD, also thinks tape strips are likely to become routine clinical tools.

“Once the basis research, validation, and data are out, I think numerous companies will be ready to develop machines for more quick and easy processing, compared to the more labor intensive process that is used today for research,” explained Dr. Clausen, who is in the department of dermatology, Bispebjerb Hospital, University of Copenhagen.

She considers tape strips particularly promising for children, but she thinks the biomarker profiling made possible by these strips might be leading to personalized treatment programs for dermatologic diseases.

“What we need is further validation; which tape to use, how deep, and the importance of storage, which is a big issue in the clinic,” Dr. Clausen said in an interview.

Dr. Guttman-Yassky has financial relationships with multiple pharmaceutical companies, including those with therapies for psoriasis.

SOURCE: Guttman-Yassky E et al. J Allergy Clin Immunol. 2020 Jul 9. doi: 10.1016/j.jaci.2020.05.048.

Collecting cells from the skin surface with adhesive tape strips is demonstrating a level of accuracy that is rivaling skin biopsies for atopic dermatitis and psoriasis, promising a minimally invasive approach for monitoring these and potentially other dermatologic diseases, according to the latest advances with this approach.

Courtesy Mount Sinai Health System

“Tape strips are not going to fully replace biopsies, but we think they will have an important role in diagnosing and monitoring response to therapy by avoiding the potential scarring and pain of biopsy,” reported Emma Guttman-Yassky, MD, PhD, professor of dermatology and director of the laboratory inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai Medical Center, New York.

The concept of using adhesive strips to remove surface skin cells for clinical study has been around for more than 20 years, but there has been recent progress. A newly published study, which compared skin from patients with atopic dermatitis (AD) or psoriasis with that of controls, was characterized as “the most comprehensive tape strip molecular profiling in any inflammatory skin disease to date and the first to fully characterize and compare AD to psoriasis,” wrote Dr. Guttman-Yassky, the senior author, and coauthors.

It also appears to be a leap forward. RNA sequencing detected thousands of differentially expressed genes reflecting immune and barrier biomarkers characteristic of the molecular phenotypes of atopic dermatitis and psoriasis. These were not only found to be consistent with biopsy studies but identified additional unique genes and pathways relevant to their pathological signature.

“In the past, the success rate for transcriptome sequencing even for a more limited panel of proteins was approaching 50% when considering both lesional, nonlesional skin, and healthy skin, but we are now approaching 100% for sample recovery and for analysis of RNA and genes,” Dr. Guttman-Yassky said in an interview.

Tissue samples were obtained with tape strips from lesional and nonlesional skin from 20 patients with AD and 20 patients with psoriasis. Compared with 20 tape strips from controls, they were evaluated with RNA sequencing followed by quantitative real-time polymerase chain reaction of immune and barrier biomarkers.

The sample recovery rate was 96% overall and 95% or better regardless of whether the skin was lesional or nonlesional.

With RNA sequencing of more than 20,000 transcripts, including multiple cellular, immune, and barrier biomarkers, an enormous amount of data was generated, but the key finding is that these diseases are readily distinguished with profiling based on tape strips.

Although numerous biomarkers were shared, “tape strips completely discriminate between atopic dermatitis and psoriasis with a degree of reliability that is comparable to skin biopsy,” Dr. Guttman-Yassky said.

One of the biomarkers, expression of nitric oxide synthase 2/inducible nitric oxide synthase, distinguished AD from psoriasis with 100% accuracy. As previously reported in biopsy studies, other biomarkers collectively associated AD with a profile related to a Th2-type inflammatory response and psoriasis with a Th17-type inflammatory response.

Tape strips also confirmed significant pathology in the nonlesional as well as the lesional skin of patients with AD or psoriasis. This included an increase in Th2-type products, such as interleukin-4 and IL-13, in nonlesional skin of atopic dermatitis and Th17-type products, such as IL-17, in nonlesional skin of psoriasis.

Some biomarkers of AD and psoriasis had an even greater differentiation in tape strips than previously reported from biopsy studies, according to Dr. Guttman-Yassky. In this study, tape strips also captured more differentially expressed genes than previously reported with biopsies.

One potential limitation of tape strips is that the RNA isolation process is time consuming, but this might be less of an issue in routine clinical use if there is a more refined number of biomarkers that are targeted or if technological improvements simplify processing, Dr. Guttman-Yassky pointed out.

To develop clinical utility for tape strips beyond AD and psoriasis, more work is needed to standardize the depth of sampling, which is variable with tape strips, she noted. Depth is relevant to the analysis of gene expression and mRNA activity of each dermatologic disease.

“Tape strips remain a research tool for now, but we do think that this technique can be refined and employed for clinical purposes, including diagnosis and monitoring response to treatment,” she said.

Relative to biopsy, the advantages are not difficult to envision. Dr. Guttman-Yassky, who recently published a study of tape strips for evaluating AD in children emphasized that tape strips are generally painless.

“Patients really do not mind tape strips,” she said. Although she believes that tape strips are providing unique insight into the pathology of inflammatory diseases not necessarily available with biopsy, she emphasized the practical value. Not least, “these could really help when the goal is to evaluate response to therapy over time.”

Another investigator who has conducted studies with tape strips, Maja-Lisa Clausen, MD, PhD, also thinks tape strips are likely to become routine clinical tools.

“Once the basis research, validation, and data are out, I think numerous companies will be ready to develop machines for more quick and easy processing, compared to the more labor intensive process that is used today for research,” explained Dr. Clausen, who is in the department of dermatology, Bispebjerb Hospital, University of Copenhagen.

She considers tape strips particularly promising for children, but she thinks the biomarker profiling made possible by these strips might be leading to personalized treatment programs for dermatologic diseases.

“What we need is further validation; which tape to use, how deep, and the importance of storage, which is a big issue in the clinic,” Dr. Clausen said in an interview.

Dr. Guttman-Yassky has financial relationships with multiple pharmaceutical companies, including those with therapies for psoriasis.

SOURCE: Guttman-Yassky E et al. J Allergy Clin Immunol. 2020 Jul 9. doi: 10.1016/j.jaci.2020.05.048.

Collecting cells from the skin surface with adhesive tape strips is demonstrating a level of accuracy that is rivaling skin biopsies for atopic dermatitis and psoriasis, promising a minimally invasive approach for monitoring these and potentially other dermatologic diseases, according to the latest advances with this approach.

Courtesy Mount Sinai Health System

“Tape strips are not going to fully replace biopsies, but we think they will have an important role in diagnosing and monitoring response to therapy by avoiding the potential scarring and pain of biopsy,” reported Emma Guttman-Yassky, MD, PhD, professor of dermatology and director of the laboratory inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai Medical Center, New York.

The concept of using adhesive strips to remove surface skin cells for clinical study has been around for more than 20 years, but there has been recent progress. A newly published study, which compared skin from patients with atopic dermatitis (AD) or psoriasis with that of controls, was characterized as “the most comprehensive tape strip molecular profiling in any inflammatory skin disease to date and the first to fully characterize and compare AD to psoriasis,” wrote Dr. Guttman-Yassky, the senior author, and coauthors.

It also appears to be a leap forward. RNA sequencing detected thousands of differentially expressed genes reflecting immune and barrier biomarkers characteristic of the molecular phenotypes of atopic dermatitis and psoriasis. These were not only found to be consistent with biopsy studies but identified additional unique genes and pathways relevant to their pathological signature.

“In the past, the success rate for transcriptome sequencing even for a more limited panel of proteins was approaching 50% when considering both lesional, nonlesional skin, and healthy skin, but we are now approaching 100% for sample recovery and for analysis of RNA and genes,” Dr. Guttman-Yassky said in an interview.

Tissue samples were obtained with tape strips from lesional and nonlesional skin from 20 patients with AD and 20 patients with psoriasis. Compared with 20 tape strips from controls, they were evaluated with RNA sequencing followed by quantitative real-time polymerase chain reaction of immune and barrier biomarkers.

The sample recovery rate was 96% overall and 95% or better regardless of whether the skin was lesional or nonlesional.

With RNA sequencing of more than 20,000 transcripts, including multiple cellular, immune, and barrier biomarkers, an enormous amount of data was generated, but the key finding is that these diseases are readily distinguished with profiling based on tape strips.

Although numerous biomarkers were shared, “tape strips completely discriminate between atopic dermatitis and psoriasis with a degree of reliability that is comparable to skin biopsy,” Dr. Guttman-Yassky said.

One of the biomarkers, expression of nitric oxide synthase 2/inducible nitric oxide synthase, distinguished AD from psoriasis with 100% accuracy. As previously reported in biopsy studies, other biomarkers collectively associated AD with a profile related to a Th2-type inflammatory response and psoriasis with a Th17-type inflammatory response.

Tape strips also confirmed significant pathology in the nonlesional as well as the lesional skin of patients with AD or psoriasis. This included an increase in Th2-type products, such as interleukin-4 and IL-13, in nonlesional skin of atopic dermatitis and Th17-type products, such as IL-17, in nonlesional skin of psoriasis.

Some biomarkers of AD and psoriasis had an even greater differentiation in tape strips than previously reported from biopsy studies, according to Dr. Guttman-Yassky. In this study, tape strips also captured more differentially expressed genes than previously reported with biopsies.

One potential limitation of tape strips is that the RNA isolation process is time consuming, but this might be less of an issue in routine clinical use if there is a more refined number of biomarkers that are targeted or if technological improvements simplify processing, Dr. Guttman-Yassky pointed out.

To develop clinical utility for tape strips beyond AD and psoriasis, more work is needed to standardize the depth of sampling, which is variable with tape strips, she noted. Depth is relevant to the analysis of gene expression and mRNA activity of each dermatologic disease.

“Tape strips remain a research tool for now, but we do think that this technique can be refined and employed for clinical purposes, including diagnosis and monitoring response to treatment,” she said.

Relative to biopsy, the advantages are not difficult to envision. Dr. Guttman-Yassky, who recently published a study of tape strips for evaluating AD in children emphasized that tape strips are generally painless.

“Patients really do not mind tape strips,” she said. Although she believes that tape strips are providing unique insight into the pathology of inflammatory diseases not necessarily available with biopsy, she emphasized the practical value. Not least, “these could really help when the goal is to evaluate response to therapy over time.”

Another investigator who has conducted studies with tape strips, Maja-Lisa Clausen, MD, PhD, also thinks tape strips are likely to become routine clinical tools.

“Once the basis research, validation, and data are out, I think numerous companies will be ready to develop machines for more quick and easy processing, compared to the more labor intensive process that is used today for research,” explained Dr. Clausen, who is in the department of dermatology, Bispebjerb Hospital, University of Copenhagen.

She considers tape strips particularly promising for children, but she thinks the biomarker profiling made possible by these strips might be leading to personalized treatment programs for dermatologic diseases.

“What we need is further validation; which tape to use, how deep, and the importance of storage, which is a big issue in the clinic,” Dr. Clausen said in an interview.

Dr. Guttman-Yassky has financial relationships with multiple pharmaceutical companies, including those with therapies for psoriasis.

SOURCE: Guttman-Yassky E et al. J Allergy Clin Immunol. 2020 Jul 9. doi: 10.1016/j.jaci.2020.05.048.

Polycystic ovarian syndrome (PCOS) was associated with a nearly doubled risk of developing psoriasis in a propensity score–matched analysis conducted in Taiwan.

PCOS is characterized by androgen elevation that can lead to insulin resistance and metabolic syndrome, which have also been associated with an increased risk of psoriasis. Previous retrospective analyses have suggested an increased risk of psoriasis associated with PCOS, and psoriasis patients with PCOS have been reported to have more severe skin lesions, compared with those who do not have PCOS.

“The incidence of psoriasis is indeed higher in the PCOS group than in the control group, and the comorbidities related to metabolic syndrome did not modify the adjusted hazard ratio,” said Ming-Li Chen, during her presentation of the study results at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. Dr. Chen is at Chung Shan Medical University in Taiwan.

The researchers analyzed 1 million randomly selected records from Taiwan’s Longitudinal Health Insurance database, a subset of the country’s National Health Insurance Program. Between 2000 and 2012, they identified a case group with at least three outpatient diagnoses or one inpatient diagnosis of PCOS; they then compared each with four patients who did not have PCOS who were matched by age and index year. The mean age in both groups was about 27 years.

The mean follow-up times were 6.99 years for 4,707 cases and 6.94 years for 18,828 controls. Comorbidities were slightly higher in the PCOS group, including asthma (6.7% vs. 4.9%; P less than .001), chronic obstructive pulmonary disease (14% vs. 11%; P less than .001), chronic liver disease (8.0% vs. 5.0%; P less than .001), diabetes mellitus (3.0% vs. 1.4%; P less than .001), hypertension (2.4% vs. 1.5%; P less than .001), hyperlipidemia (5.4% vs. 2.5%; P less than .001), depression (5.4% vs. 3.9%; P less than .001), and sleep apnea (0.23% vs. 0.10%; P = .040).

There was a higher cumulative incidence of psoriasis in the PCOS group (adjusted hazard ratio, 2.07; 95% confidence interval, 1.25-3.44). Other factors associated with increased risk of psoriasis were advanced age (greater than 50 years old; aHR, 14.13; 95% CI, 1.8-110.7) and having a cancer diagnosis (aHR, 11.72; 95% CI, 2.87-47.9).

When PCOS patients were stratified by age, the researchers noted a higher risk of psoriasis among those 20 years or younger (aHR, 4.02; 95% CI, 1.16-13.9) than among those aged 20-50 years (aHR, 1.88; 95% CI, 1.07-3.29). Among those older than 50 years, there was no significantly increased risk, although the number of psoriasis diagnoses and population sizes were small in the latter category. Among patients with PCOS, a cancer diagnosis was not associated with a statistically significant increased risk of psoriasis.

The mechanisms underlying the association between PCOS and psoriasis should be studied further, she noted.

Following Dr. Chen’s prerecorded presentation, there was a live discussion session led by Alice Gottlieb, MD, PhD, medical director of Mount Sinai Beth Israel Dermatology, New York, and Ennio Lubrano, MD, associate professor of rheumatology at the University of Molise (Italy). Dr. Gottlieb noted that the study did not appear to account for weight in the association between PCOS and psoriasis, since heavier people are known to be at greater risk of developing psoriasis. Dr. Chen acknowledged that the study had no records of BMI or weight.

Dr. Gottlieb also wondered if treatment of PCOS led to any improvements in psoriasis in patients with the two diagnoses. “If we treat PCOS, does the psoriasis get better?” Again, the study did not address the question. “We didn’t follow up on therapies,” Dr. Chen said.

Dr. Chen reported no relevant financial disclosures. Dr. Gottlieb is a consultant, advisory board member and/or speaker for AbbVie, Allergan, Avotres Therapeutics, Beiersdorf, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Incyte, Janssen, Leo, Novartis, Reddy Labs, Sun Pharmaceutical Industries, UCB Pharma and Xbiotech. She has received research or educational grants from Boehringer Ingelheim, Incyte, Janssen, Novartis and Xbiotech.

Polycystic ovarian syndrome (PCOS) was associated with a nearly doubled risk of developing psoriasis in a propensity score–matched analysis conducted in Taiwan.

PCOS is characterized by androgen elevation that can lead to insulin resistance and metabolic syndrome, which have also been associated with an increased risk of psoriasis. Previous retrospective analyses have suggested an increased risk of psoriasis associated with PCOS, and psoriasis patients with PCOS have been reported to have more severe skin lesions, compared with those who do not have PCOS.

“The incidence of psoriasis is indeed higher in the PCOS group than in the control group, and the comorbidities related to metabolic syndrome did not modify the adjusted hazard ratio,” said Ming-Li Chen, during her presentation of the study results at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. Dr. Chen is at Chung Shan Medical University in Taiwan.

The researchers analyzed 1 million randomly selected records from Taiwan’s Longitudinal Health Insurance database, a subset of the country’s National Health Insurance Program. Between 2000 and 2012, they identified a case group with at least three outpatient diagnoses or one inpatient diagnosis of PCOS; they then compared each with four patients who did not have PCOS who were matched by age and index year. The mean age in both groups was about 27 years.

The mean follow-up times were 6.99 years for 4,707 cases and 6.94 years for 18,828 controls. Comorbidities were slightly higher in the PCOS group, including asthma (6.7% vs. 4.9%; P less than .001), chronic obstructive pulmonary disease (14% vs. 11%; P less than .001), chronic liver disease (8.0% vs. 5.0%; P less than .001), diabetes mellitus (3.0% vs. 1.4%; P less than .001), hypertension (2.4% vs. 1.5%; P less than .001), hyperlipidemia (5.4% vs. 2.5%; P less than .001), depression (5.4% vs. 3.9%; P less than .001), and sleep apnea (0.23% vs. 0.10%; P = .040).

There was a higher cumulative incidence of psoriasis in the PCOS group (adjusted hazard ratio, 2.07; 95% confidence interval, 1.25-3.44). Other factors associated with increased risk of psoriasis were advanced age (greater than 50 years old; aHR, 14.13; 95% CI, 1.8-110.7) and having a cancer diagnosis (aHR, 11.72; 95% CI, 2.87-47.9).

When PCOS patients were stratified by age, the researchers noted a higher risk of psoriasis among those 20 years or younger (aHR, 4.02; 95% CI, 1.16-13.9) than among those aged 20-50 years (aHR, 1.88; 95% CI, 1.07-3.29). Among those older than 50 years, there was no significantly increased risk, although the number of psoriasis diagnoses and population sizes were small in the latter category. Among patients with PCOS, a cancer diagnosis was not associated with a statistically significant increased risk of psoriasis.

The mechanisms underlying the association between PCOS and psoriasis should be studied further, she noted.

Following Dr. Chen’s prerecorded presentation, there was a live discussion session led by Alice Gottlieb, MD, PhD, medical director of Mount Sinai Beth Israel Dermatology, New York, and Ennio Lubrano, MD, associate professor of rheumatology at the University of Molise (Italy). Dr. Gottlieb noted that the study did not appear to account for weight in the association between PCOS and psoriasis, since heavier people are known to be at greater risk of developing psoriasis. Dr. Chen acknowledged that the study had no records of BMI or weight.

Dr. Gottlieb also wondered if treatment of PCOS led to any improvements in psoriasis in patients with the two diagnoses. “If we treat PCOS, does the psoriasis get better?” Again, the study did not address the question. “We didn’t follow up on therapies,” Dr. Chen said.

Dr. Chen reported no relevant financial disclosures. Dr. Gottlieb is a consultant, advisory board member and/or speaker for AbbVie, Allergan, Avotres Therapeutics, Beiersdorf, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Incyte, Janssen, Leo, Novartis, Reddy Labs, Sun Pharmaceutical Industries, UCB Pharma and Xbiotech. She has received research or educational grants from Boehringer Ingelheim, Incyte, Janssen, Novartis and Xbiotech.

Polycystic ovarian syndrome (PCOS) was associated with a nearly doubled risk of developing psoriasis in a propensity score–matched analysis conducted in Taiwan.

PCOS is characterized by androgen elevation that can lead to insulin resistance and metabolic syndrome, which have also been associated with an increased risk of psoriasis. Previous retrospective analyses have suggested an increased risk of psoriasis associated with PCOS, and psoriasis patients with PCOS have been reported to have more severe skin lesions, compared with those who do not have PCOS.

“The incidence of psoriasis is indeed higher in the PCOS group than in the control group, and the comorbidities related to metabolic syndrome did not modify the adjusted hazard ratio,” said Ming-Li Chen, during her presentation of the study results at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis. Dr. Chen is at Chung Shan Medical University in Taiwan.

The researchers analyzed 1 million randomly selected records from Taiwan’s Longitudinal Health Insurance database, a subset of the country’s National Health Insurance Program. Between 2000 and 2012, they identified a case group with at least three outpatient diagnoses or one inpatient diagnosis of PCOS; they then compared each with four patients who did not have PCOS who were matched by age and index year. The mean age in both groups was about 27 years.

The mean follow-up times were 6.99 years for 4,707 cases and 6.94 years for 18,828 controls. Comorbidities were slightly higher in the PCOS group, including asthma (6.7% vs. 4.9%; P less than .001), chronic obstructive pulmonary disease (14% vs. 11%; P less than .001), chronic liver disease (8.0% vs. 5.0%; P less than .001), diabetes mellitus (3.0% vs. 1.4%; P less than .001), hypertension (2.4% vs. 1.5%; P less than .001), hyperlipidemia (5.4% vs. 2.5%; P less than .001), depression (5.4% vs. 3.9%; P less than .001), and sleep apnea (0.23% vs. 0.10%; P = .040).

There was a higher cumulative incidence of psoriasis in the PCOS group (adjusted hazard ratio, 2.07; 95% confidence interval, 1.25-3.44). Other factors associated with increased risk of psoriasis were advanced age (greater than 50 years old; aHR, 14.13; 95% CI, 1.8-110.7) and having a cancer diagnosis (aHR, 11.72; 95% CI, 2.87-47.9).

When PCOS patients were stratified by age, the researchers noted a higher risk of psoriasis among those 20 years or younger (aHR, 4.02; 95% CI, 1.16-13.9) than among those aged 20-50 years (aHR, 1.88; 95% CI, 1.07-3.29). Among those older than 50 years, there was no significantly increased risk, although the number of psoriasis diagnoses and population sizes were small in the latter category. Among patients with PCOS, a cancer diagnosis was not associated with a statistically significant increased risk of psoriasis.

The mechanisms underlying the association between PCOS and psoriasis should be studied further, she noted.

Following Dr. Chen’s prerecorded presentation, there was a live discussion session led by Alice Gottlieb, MD, PhD, medical director of Mount Sinai Beth Israel Dermatology, New York, and Ennio Lubrano, MD, associate professor of rheumatology at the University of Molise (Italy). Dr. Gottlieb noted that the study did not appear to account for weight in the association between PCOS and psoriasis, since heavier people are known to be at greater risk of developing psoriasis. Dr. Chen acknowledged that the study had no records of BMI or weight.

Dr. Gottlieb also wondered if treatment of PCOS led to any improvements in psoriasis in patients with the two diagnoses. “If we treat PCOS, does the psoriasis get better?” Again, the study did not address the question. “We didn’t follow up on therapies,” Dr. Chen said.

Dr. Chen reported no relevant financial disclosures. Dr. Gottlieb is a consultant, advisory board member and/or speaker for AbbVie, Allergan, Avotres Therapeutics, Beiersdorf, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Incyte, Janssen, Leo, Novartis, Reddy Labs, Sun Pharmaceutical Industries, UCB Pharma and Xbiotech. She has received research or educational grants from Boehringer Ingelheim, Incyte, Janssen, Novartis and Xbiotech.

Topical agents, alternative medicine, and disease severity assessment are the subjects of the latest updated set of guidelines for the management and treatment of psoriasis issued jointly by the American Academy of Dermatology and the National Psoriasis Foundation.

©Rodd100/thinkstockphotos.com

The guidelines, published in the Journal of the American Academy of Dermatology, focus on treatment for adults, and follow the release of other AAD-NPF guidelines on biologics for psoriasis, psoriasis-related comorbidities, pediatric psoriasis, and phototherapy in 2019, and earlier this year, guidelines for systemic nonbiologic treatments. The latest guidelines’ section on topical treatment outlines evidence for the efficacy, effectiveness, and adverse events related to topical steroids, topical tacrolimus and pimecrolimus, vitamin D analogues, tazarotene, moisturizers, salicylic acid, anthralin, coal tar, combinations with biologic agents, and combinations with nonbiologic treatments (methotrexate, cyclosporine, acitretin, and apremilast).

The guidelines noted the “key role” of topical corticosteroids in treating psoriasis “especially for localized disease,” and include a review of the data on low-, moderate-, high-, and ultrahigh-potency topical steroids for psoriasis.

In general, all topical steroids can be used in combination with biologics, according to the guidelines, but the strongest recommendations based on the latest evidence include the addition of an ultra-high potency topical corticosteroid to standard dose etanercept for 12 weeks. Currently, 11 biologics are approved by the Food and Drug Administration for the treatment of psoriasis.

In addition, “while not FDA approved for psoriasis, the topical calcineurin inhibitors tacrolimus and pimecrolimus are often employed in the treatment of psoriasis,” can be helpful for “thinner skin such as facial and intertriginous areas,” and can be steroid sparing when used for more than 4 weeks, according to the guidelines.

Don’t discount the role of patient preferences when choosing topical treatments, the authors noted. “The optimal vehicle choice is the one the patient is mostly likely to use.”

The guidelines also address the evidence for effectiveness, and adverse events in the use of several alternative medicines for psoriasis including traditional Chinese medicine, and the herbal therapies aloe vera and St. John’s wort, as well as the potential role of dietary supplements including fish oil, vitamin D, turmeric, and zinc in managing psoriasis, and the potential role of a gluten-free diet.

In general, research on the efficacy, effectiveness, and potential adverse effects of these strategies are limited, according to the guidelines, although many patients express interest in supplements and herbal products. For example, “Many patients ask about the overall role of vitamin D in skin health. Rather than adding oral vitamin D supplementation, topical therapy with vitamin D agents is effective for the treatment of psoriasis,” the authors noted.

In addition, they noted that mind/body strategies, namely hypnosis and stress reduction or meditation techniques, have been shown to improve symptoms and can be helpful for some patients, but clinical evidence is limited.

The guidelines also addressed methods for assessing disease severity in psoriasis. They recommended using body surface area (BSA) to assess psoriasis severity and patient response to treatment in the clinical setting. However, BSA is a provider assessment tool that “does not take into account location on the body, clinical characteristics of the plaques, symptoms, or quality of life issues,” the authors noted. The Psoriasis Area and Severity Index (PASI) measures erythema, induration, and scaling and is more suited to assessing psoriasis severity and response to treatment in clinical trials rather than in practice, they said.

Prior AAD guidelines on psoriasis were published more than 10 years ago, and major developments including the availability of new biologic drugs and new data on comorbidities have been recognized in the past decade, working group cochair and author of the guidelines Alan Menter, MD, said in an interview.

The key game-changers from previous guidelines include the full section published on comorbidities plus the development of two new important cytokine classes: three IL-17 drugs and three new IL-23 drugs now available for moderate to severe psoriasis, said Dr. Menter, chairman of the division of dermatology at Baylor University Medical Center, Dallas.

Barriers to implementing the guidelines in practice may occur when “third party payers make the decision on which of the 11 biologic drugs now approved for moderate to severe psoriasis should be used,” he noted.

As for next steps in psoriasis studies, “new biomarker research is currently underway,” Dr. Menter said. With 11 biologic agents new formally approved by the FDA for moderate to severe psoriasis, the next steps are to determine which drug is likely to be the most appropriate for each individual patient.

Dr. Menter disclosed relationships with multiple companies that develop and manufacture psoriasis therapies, including Abbott Labs, AbbVie, Amgen, Eli Lilly and Company, Galderma USA, Janssen Pharmaceuticals, LEO Pharma US, Menlo Therapeutics, and Novartis. The updated guidelines were designed by a multidisciplinary work group of psoriasis experts including dermatologists, a rheumatologist, a cardiologist, and representatives from a patient advocacy organization.
 

SOURCE: Elmets CA et al. J Am Acad Dermatol. 2020 Jul 29. doi: 10.1016/j.jaad.2020.07.087.

Topical agents, alternative medicine, and disease severity assessment are the subjects of the latest updated set of guidelines for the management and treatment of psoriasis issued jointly by the American Academy of Dermatology and the National Psoriasis Foundation.

©Rodd100/thinkstockphotos.com

The guidelines, published in the Journal of the American Academy of Dermatology, focus on treatment for adults, and follow the release of other AAD-NPF guidelines on biologics for psoriasis, psoriasis-related comorbidities, pediatric psoriasis, and phototherapy in 2019, and earlier this year, guidelines for systemic nonbiologic treatments. The latest guidelines’ section on topical treatment outlines evidence for the efficacy, effectiveness, and adverse events related to topical steroids, topical tacrolimus and pimecrolimus, vitamin D analogues, tazarotene, moisturizers, salicylic acid, anthralin, coal tar, combinations with biologic agents, and combinations with nonbiologic treatments (methotrexate, cyclosporine, acitretin, and apremilast).

The guidelines noted the “key role” of topical corticosteroids in treating psoriasis “especially for localized disease,” and include a review of the data on low-, moderate-, high-, and ultrahigh-potency topical steroids for psoriasis.

In general, all topical steroids can be used in combination with biologics, according to the guidelines, but the strongest recommendations based on the latest evidence include the addition of an ultra-high potency topical corticosteroid to standard dose etanercept for 12 weeks. Currently, 11 biologics are approved by the Food and Drug Administration for the treatment of psoriasis.

In addition, “while not FDA approved for psoriasis, the topical calcineurin inhibitors tacrolimus and pimecrolimus are often employed in the treatment of psoriasis,” can be helpful for “thinner skin such as facial and intertriginous areas,” and can be steroid sparing when used for more than 4 weeks, according to the guidelines.

Don’t discount the role of patient preferences when choosing topical treatments, the authors noted. “The optimal vehicle choice is the one the patient is mostly likely to use.”

The guidelines also address the evidence for effectiveness, and adverse events in the use of several alternative medicines for psoriasis including traditional Chinese medicine, and the herbal therapies aloe vera and St. John’s wort, as well as the potential role of dietary supplements including fish oil, vitamin D, turmeric, and zinc in managing psoriasis, and the potential role of a gluten-free diet.

In general, research on the efficacy, effectiveness, and potential adverse effects of these strategies are limited, according to the guidelines, although many patients express interest in supplements and herbal products. For example, “Many patients ask about the overall role of vitamin D in skin health. Rather than adding oral vitamin D supplementation, topical therapy with vitamin D agents is effective for the treatment of psoriasis,” the authors noted.

In addition, they noted that mind/body strategies, namely hypnosis and stress reduction or meditation techniques, have been shown to improve symptoms and can be helpful for some patients, but clinical evidence is limited.

The guidelines also addressed methods for assessing disease severity in psoriasis. They recommended using body surface area (BSA) to assess psoriasis severity and patient response to treatment in the clinical setting. However, BSA is a provider assessment tool that “does not take into account location on the body, clinical characteristics of the plaques, symptoms, or quality of life issues,” the authors noted. The Psoriasis Area and Severity Index (PASI) measures erythema, induration, and scaling and is more suited to assessing psoriasis severity and response to treatment in clinical trials rather than in practice, they said.

Prior AAD guidelines on psoriasis were published more than 10 years ago, and major developments including the availability of new biologic drugs and new data on comorbidities have been recognized in the past decade, working group cochair and author of the guidelines Alan Menter, MD, said in an interview.

The key game-changers from previous guidelines include the full section published on comorbidities plus the development of two new important cytokine classes: three IL-17 drugs and three new IL-23 drugs now available for moderate to severe psoriasis, said Dr. Menter, chairman of the division of dermatology at Baylor University Medical Center, Dallas.

Barriers to implementing the guidelines in practice may occur when “third party payers make the decision on which of the 11 biologic drugs now approved for moderate to severe psoriasis should be used,” he noted.

As for next steps in psoriasis studies, “new biomarker research is currently underway,” Dr. Menter said. With 11 biologic agents new formally approved by the FDA for moderate to severe psoriasis, the next steps are to determine which drug is likely to be the most appropriate for each individual patient.

Dr. Menter disclosed relationships with multiple companies that develop and manufacture psoriasis therapies, including Abbott Labs, AbbVie, Amgen, Eli Lilly and Company, Galderma USA, Janssen Pharmaceuticals, LEO Pharma US, Menlo Therapeutics, and Novartis. The updated guidelines were designed by a multidisciplinary work group of psoriasis experts including dermatologists, a rheumatologist, a cardiologist, and representatives from a patient advocacy organization.
 

SOURCE: Elmets CA et al. J Am Acad Dermatol. 2020 Jul 29. doi: 10.1016/j.jaad.2020.07.087.

Topical agents, alternative medicine, and disease severity assessment are the subjects of the latest updated set of guidelines for the management and treatment of psoriasis issued jointly by the American Academy of Dermatology and the National Psoriasis Foundation.

©Rodd100/thinkstockphotos.com

The guidelines, published in the Journal of the American Academy of Dermatology, focus on treatment for adults, and follow the release of other AAD-NPF guidelines on biologics for psoriasis, psoriasis-related comorbidities, pediatric psoriasis, and phototherapy in 2019, and earlier this year, guidelines for systemic nonbiologic treatments. The latest guidelines’ section on topical treatment outlines evidence for the efficacy, effectiveness, and adverse events related to topical steroids, topical tacrolimus and pimecrolimus, vitamin D analogues, tazarotene, moisturizers, salicylic acid, anthralin, coal tar, combinations with biologic agents, and combinations with nonbiologic treatments (methotrexate, cyclosporine, acitretin, and apremilast).

The guidelines noted the “key role” of topical corticosteroids in treating psoriasis “especially for localized disease,” and include a review of the data on low-, moderate-, high-, and ultrahigh-potency topical steroids for psoriasis.

In general, all topical steroids can be used in combination with biologics, according to the guidelines, but the strongest recommendations based on the latest evidence include the addition of an ultra-high potency topical corticosteroid to standard dose etanercept for 12 weeks. Currently, 11 biologics are approved by the Food and Drug Administration for the treatment of psoriasis.

In addition, “while not FDA approved for psoriasis, the topical calcineurin inhibitors tacrolimus and pimecrolimus are often employed in the treatment of psoriasis,” can be helpful for “thinner skin such as facial and intertriginous areas,” and can be steroid sparing when used for more than 4 weeks, according to the guidelines.

Don’t discount the role of patient preferences when choosing topical treatments, the authors noted. “The optimal vehicle choice is the one the patient is mostly likely to use.”

The guidelines also address the evidence for effectiveness, and adverse events in the use of several alternative medicines for psoriasis including traditional Chinese medicine, and the herbal therapies aloe vera and St. John’s wort, as well as the potential role of dietary supplements including fish oil, vitamin D, turmeric, and zinc in managing psoriasis, and the potential role of a gluten-free diet.

In general, research on the efficacy, effectiveness, and potential adverse effects of these strategies are limited, according to the guidelines, although many patients express interest in supplements and herbal products. For example, “Many patients ask about the overall role of vitamin D in skin health. Rather than adding oral vitamin D supplementation, topical therapy with vitamin D agents is effective for the treatment of psoriasis,” the authors noted.

In addition, they noted that mind/body strategies, namely hypnosis and stress reduction or meditation techniques, have been shown to improve symptoms and can be helpful for some patients, but clinical evidence is limited.

The guidelines also addressed methods for assessing disease severity in psoriasis. They recommended using body surface area (BSA) to assess psoriasis severity and patient response to treatment in the clinical setting. However, BSA is a provider assessment tool that “does not take into account location on the body, clinical characteristics of the plaques, symptoms, or quality of life issues,” the authors noted. The Psoriasis Area and Severity Index (PASI) measures erythema, induration, and scaling and is more suited to assessing psoriasis severity and response to treatment in clinical trials rather than in practice, they said.

Prior AAD guidelines on psoriasis were published more than 10 years ago, and major developments including the availability of new biologic drugs and new data on comorbidities have been recognized in the past decade, working group cochair and author of the guidelines Alan Menter, MD, said in an interview.

The key game-changers from previous guidelines include the full section published on comorbidities plus the development of two new important cytokine classes: three IL-17 drugs and three new IL-23 drugs now available for moderate to severe psoriasis, said Dr. Menter, chairman of the division of dermatology at Baylor University Medical Center, Dallas.

Barriers to implementing the guidelines in practice may occur when “third party payers make the decision on which of the 11 biologic drugs now approved for moderate to severe psoriasis should be used,” he noted.

As for next steps in psoriasis studies, “new biomarker research is currently underway,” Dr. Menter said. With 11 biologic agents new formally approved by the FDA for moderate to severe psoriasis, the next steps are to determine which drug is likely to be the most appropriate for each individual patient.

Dr. Menter disclosed relationships with multiple companies that develop and manufacture psoriasis therapies, including Abbott Labs, AbbVie, Amgen, Eli Lilly and Company, Galderma USA, Janssen Pharmaceuticals, LEO Pharma US, Menlo Therapeutics, and Novartis. The updated guidelines were designed by a multidisciplinary work group of psoriasis experts including dermatologists, a rheumatologist, a cardiologist, and representatives from a patient advocacy organization.
 

SOURCE: Elmets CA et al. J Am Acad Dermatol. 2020 Jul 29. doi: 10.1016/j.jaad.2020.07.087.

Treatment of psoriasis with biologics was associated with a reduced risk of developing psoriatic arthritis compared with conventional disease-modifying antirheumatic drugs (DMARDs), in a single center retrospective analysis in Argentina that followed patients for almost 2 decades.

About 30%-40% of patients with psoriasis go on to develop psoriatic arthritis (PsA), usually on average about 10 years after the onset of psoriasis. One potential mechanism of PsA onset is through enthesitis, which has been described at subclinical levels in psoriasis.

“It could be speculated that treatment with biologics in patients with psoriasis could prevent the development of psoriatic arthritis, perhaps by inhibiting the subclinical development of enthesitis,” Luciano Lo Giudice, MD, a rheumatology fellow at Hospital Italiano de Buenos Aires, said during his presentation at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

Although these results do not prove that treatment of the underlying disease delays progression to PsA, it is suggestive, and highlights an emerging field of research, according to Diamant Thaçi, MD, PhD, professor of medicine at University Hospital Schleswig-Holstein, Germany, who led a live discussion following a prerecorded presentation of the results. “We’re going in this direction – how can we prevent psoriatic arthritis, how can we delay it. We are just starting to think about this,” Dr. Thaçi said in an interview.

The researchers examined medical records of 1,626 patients with psoriasis treated at their center between 2000 and 2019, with a total of 15,152 years of follow-up. Of these patients, 1,293 were treated with topical medication, 229 with conventional DMARDs (methotrexate in 77%, cyclosporine in 13%, and both in 10%), and 104 with biologics, including etanercept (34%), secukinumab (20%), adalimumab (20%), ustekinumab (12%), ixekizumab (9%), and infliximab (5%).

They found that 11% in the topical treatment group developed PsA, as did 3.5% in the conventional DMARD group, 1.9% in the biologics group, and 9.1% overall. Treatment with biologics was associated with a significantly lower odds of developing PsA compared with treatment with conventional DMARDs (3 versus 17.2 per 1,000 patient-years; incidence rate ratio [IRR], 0.17; P = .0177). There was a trend toward reduced odds of developing PsA among those on biologic therapy compared with those on topicals (3 versus 9.8 per 1,000 patient-years; IRR, 0.3; P = .0588).

The researchers confirmed all medical encounters using electronic medical records and the study had a long follow-up time, but was limited by the single center and its retrospective nature. It also could not associate reduced risk with specific biologics.

The findings probably reflect the presence of subclinical PsA that many clinicians don’t see, according to Dr. Thaçi. While a dermatology practice might find PsA in 2% or 3%, or at most, 10% of patients with psoriasis, “in our department it’s about 50 to 60 percent of patients who have psoriatic arthritis, because we diagnose it early,” he said.

He found the results of the study encouraging. “It looks like some of the biologics, for example IL [interleukin]-17 or even IL-23 [blockers] may have an influence on occurrence or delay the occurrence of psoriatic arthritis.”

Dr. Thaçi noted that early treatment of skin lesions can increase the probability of longer remissions, especially with IL-23 blockers. Still, that’s no guarantee the same would hold true for PsA risk. “Skin is skin and joints are joints,” Dr. Thaçi said.

Dr. Thaçi and Dr. Lo Giudice had no relevant financial disclosures.

Treatment of psoriasis with biologics was associated with a reduced risk of developing psoriatic arthritis compared with conventional disease-modifying antirheumatic drugs (DMARDs), in a single center retrospective analysis in Argentina that followed patients for almost 2 decades.

About 30%-40% of patients with psoriasis go on to develop psoriatic arthritis (PsA), usually on average about 10 years after the onset of psoriasis. One potential mechanism of PsA onset is through enthesitis, which has been described at subclinical levels in psoriasis.

“It could be speculated that treatment with biologics in patients with psoriasis could prevent the development of psoriatic arthritis, perhaps by inhibiting the subclinical development of enthesitis,” Luciano Lo Giudice, MD, a rheumatology fellow at Hospital Italiano de Buenos Aires, said during his presentation at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

Although these results do not prove that treatment of the underlying disease delays progression to PsA, it is suggestive, and highlights an emerging field of research, according to Diamant Thaçi, MD, PhD, professor of medicine at University Hospital Schleswig-Holstein, Germany, who led a live discussion following a prerecorded presentation of the results. “We’re going in this direction – how can we prevent psoriatic arthritis, how can we delay it. We are just starting to think about this,” Dr. Thaçi said in an interview.

The researchers examined medical records of 1,626 patients with psoriasis treated at their center between 2000 and 2019, with a total of 15,152 years of follow-up. Of these patients, 1,293 were treated with topical medication, 229 with conventional DMARDs (methotrexate in 77%, cyclosporine in 13%, and both in 10%), and 104 with biologics, including etanercept (34%), secukinumab (20%), adalimumab (20%), ustekinumab (12%), ixekizumab (9%), and infliximab (5%).

They found that 11% in the topical treatment group developed PsA, as did 3.5% in the conventional DMARD group, 1.9% in the biologics group, and 9.1% overall. Treatment with biologics was associated with a significantly lower odds of developing PsA compared with treatment with conventional DMARDs (3 versus 17.2 per 1,000 patient-years; incidence rate ratio [IRR], 0.17; P = .0177). There was a trend toward reduced odds of developing PsA among those on biologic therapy compared with those on topicals (3 versus 9.8 per 1,000 patient-years; IRR, 0.3; P = .0588).

The researchers confirmed all medical encounters using electronic medical records and the study had a long follow-up time, but was limited by the single center and its retrospective nature. It also could not associate reduced risk with specific biologics.

The findings probably reflect the presence of subclinical PsA that many clinicians don’t see, according to Dr. Thaçi. While a dermatology practice might find PsA in 2% or 3%, or at most, 10% of patients with psoriasis, “in our department it’s about 50 to 60 percent of patients who have psoriatic arthritis, because we diagnose it early,” he said.

He found the results of the study encouraging. “It looks like some of the biologics, for example IL [interleukin]-17 or even IL-23 [blockers] may have an influence on occurrence or delay the occurrence of psoriatic arthritis.”

Dr. Thaçi noted that early treatment of skin lesions can increase the probability of longer remissions, especially with IL-23 blockers. Still, that’s no guarantee the same would hold true for PsA risk. “Skin is skin and joints are joints,” Dr. Thaçi said.

Dr. Thaçi and Dr. Lo Giudice had no relevant financial disclosures.

Treatment of psoriasis with biologics was associated with a reduced risk of developing psoriatic arthritis compared with conventional disease-modifying antirheumatic drugs (DMARDs), in a single center retrospective analysis in Argentina that followed patients for almost 2 decades.

About 30%-40% of patients with psoriasis go on to develop psoriatic arthritis (PsA), usually on average about 10 years after the onset of psoriasis. One potential mechanism of PsA onset is through enthesitis, which has been described at subclinical levels in psoriasis.

“It could be speculated that treatment with biologics in patients with psoriasis could prevent the development of psoriatic arthritis, perhaps by inhibiting the subclinical development of enthesitis,” Luciano Lo Giudice, MD, a rheumatology fellow at Hospital Italiano de Buenos Aires, said during his presentation at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

Although these results do not prove that treatment of the underlying disease delays progression to PsA, it is suggestive, and highlights an emerging field of research, according to Diamant Thaçi, MD, PhD, professor of medicine at University Hospital Schleswig-Holstein, Germany, who led a live discussion following a prerecorded presentation of the results. “We’re going in this direction – how can we prevent psoriatic arthritis, how can we delay it. We are just starting to think about this,” Dr. Thaçi said in an interview.

The researchers examined medical records of 1,626 patients with psoriasis treated at their center between 2000 and 2019, with a total of 15,152 years of follow-up. Of these patients, 1,293 were treated with topical medication, 229 with conventional DMARDs (methotrexate in 77%, cyclosporine in 13%, and both in 10%), and 104 with biologics, including etanercept (34%), secukinumab (20%), adalimumab (20%), ustekinumab (12%), ixekizumab (9%), and infliximab (5%).

They found that 11% in the topical treatment group developed PsA, as did 3.5% in the conventional DMARD group, 1.9% in the biologics group, and 9.1% overall. Treatment with biologics was associated with a significantly lower odds of developing PsA compared with treatment with conventional DMARDs (3 versus 17.2 per 1,000 patient-years; incidence rate ratio [IRR], 0.17; P = .0177). There was a trend toward reduced odds of developing PsA among those on biologic therapy compared with those on topicals (3 versus 9.8 per 1,000 patient-years; IRR, 0.3; P = .0588).

The researchers confirmed all medical encounters using electronic medical records and the study had a long follow-up time, but was limited by the single center and its retrospective nature. It also could not associate reduced risk with specific biologics.

The findings probably reflect the presence of subclinical PsA that many clinicians don’t see, according to Dr. Thaçi. While a dermatology practice might find PsA in 2% or 3%, or at most, 10% of patients with psoriasis, “in our department it’s about 50 to 60 percent of patients who have psoriatic arthritis, because we diagnose it early,” he said.

He found the results of the study encouraging. “It looks like some of the biologics, for example IL [interleukin]-17 or even IL-23 [blockers] may have an influence on occurrence or delay the occurrence of psoriatic arthritis.”

Dr. Thaçi noted that early treatment of skin lesions can increase the probability of longer remissions, especially with IL-23 blockers. Still, that’s no guarantee the same would hold true for PsA risk. “Skin is skin and joints are joints,” Dr. Thaçi said.

Dr. Thaçi and Dr. Lo Giudice had no relevant financial disclosures.

Pustular psoriasis is a rare condition that presents significant challenges to clinicians, not least because it comes in varied forms that are not well understood.

It has various dermatologic and rheumatologic manifestations and sometimes overlaps with plaque psoriasis. Pustular palmoplantar psoriasis (PPP) affects the palmar and plantar areas of the skin, while generalized pustular psoriasis (GPP) can affect large areas of skin and tends to be more severe, even life threatening. PPP can accompany psoriatic arthritis or can be a side effect of tumor necrosis factor (TNF) inhibitor therapy, or a non–drug-induced component of rheumatologic syndromes, according to Kristina Callis Duffin, MD, an associate professor and chair of dermatology at the University of Utah, Salt Lake City.

“Each phenotype could be considered an orphan disease, and the response to therapy is often unpredictable,” Dr. Duffin said during a session on pustular psoriasis at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

But there is some positive news. A study in 2011 of several people with GPP opened the door to better understanding the pathophysiology of pustular psoriasis. Researchers identified a causal autosomal mutation in the IL36RN gene, which encodes an antagonist to the interleukin-36 receptor (Am J Hum Genet. 2011 Sep 9;89[3]:432-7). “As a result of this paper and others, drug development in this space has recently accelerated,” Dr. Duffin said.

In fact, she added,“it’s my opinion that pustular psoriasis is now where plaque psoriasis was 20 years ago, when accelerated drug development was driving a better understanding of the pathogenesis of psoriatic disease and its comorbidities, and also driving outcome measure development.”

In another presentation at the meeting, Hervé Bachelez, MD, PhD, professor of dermatology and immunologist at the University of Paris and Saint-Louis Hospital, Paris, discussed recent advances in drug development for pustular psoriasis. He noted other recent findings of genetic variants related to the disease, including AP1S3, CARD14, and SERPINA3.

For GPP, he said, the current algorithm for management is based on weak evidence for treatments like acitretin, cyclosporine, methotrexate, and infliximab. The story is similar for other biologics, with evidence in the form of case series; open-label studies; controlled, prospective studies; or retrospective analyses. Most of the evidence has been amassed for TNF inhibitors. A retrospective study of all TNF inhibitors suggested they may be effective as induction and maintenance therapy, he noted.

Among IL-17A inhibitors, a prospective study of 12 patients in Japan found secukinumab showed efficacy against GPP, as did studies of ixekizumab and brodalumab. A small phase 3 study in Japan demonstrated efficacy for the IL-23 inhibitor guselkumab in patients with erythrodermic psoriasis and GPP (J Dermatol. 2018 May;45[5]:529-39).

The limited data are a reflection in part of the difficulty in studying GPP, since its flares tend to be more self-remitting than with psoriasis vulgaris or PPP.

There are two monoclonal antibodies against the IL-36 receptor currently being developed. A proof-of-concept study of one of them, spesolimab, showed promise against GPP, with five of seven patients reaching “clear” or “almost clear” scores on the Generalized Pustular Psoriasis Physician Global Assessment within a week after infusion and in all seven by the fourth week (N Engl J Med. 2019 Mar 7;380[10]:981-3).

With respect to PPP, the strongest evidence for conventional therapies comes from two randomized, controlled trials of cyclosporine, with response rates of 48% and 89%, compared with 19% and 21%, respectively, in the placebo groups, although the primary endpoint was poorly designed, according to Dr. Bachelez. Retinoids like etretinate and acitretin, combined with psoralen and UVA, also have some supporting evidence regarding efficacy.

Among biologics, secukinumab did not fare well in a phase 3 study of patients with PPP. A subset of patients may benefit from it, but there are no biomarkers available to identify them, Dr. Bachelez said. A phase 2 study of guselkumab in Japan told a similar story, with only weak signs of efficacy. While there are many more ongoing clinical trials evaluating treatments for PPP, which is encouraging, PPP seems to be more challenging at this stage to tackle than GPP, Dr. Bachelez added. “The genetically inherited IL-36 antagonist abnormalities are clearly driving the advances regarding the pathogenesis of the disease, mainly for GPP rather than PPP.”

Part of the efforts to develop therapies for pustular psoriasis relies on the development of new outcome measures, or adaptation of existing ones. “We have a need to adapt or develop new investigator-reported measures, we need to adapt or develop new patient-reported outcomes,” Dr. Duffin said.

Many existing measures use inconsistent language and anchoring definitions, and some may be proprietary, she added. “The language varies by sponsor and is sometimes tweaked or modified by the agencies. Often synonyms are being used … it raises questions, does it change the validity of the instrument?”

Dr. Duffin called for the research community to use the pause in clinical research during the COVID-19 pandemic to reassess the research agenda, develop consensus on performing and training for GPP and PPP assessments, develop patient-reported outcomes, and strengthen connections to industry.

Dr. Duffin and Dr. Bachelez have consulted, served on the advisory board, been a speaker for, and/or received research support from a wide range of pharmaceutical companies, including those that manufacture and develop psoriasis treatments.
 

Pustular psoriasis is a rare condition that presents significant challenges to clinicians, not least because it comes in varied forms that are not well understood.

It has various dermatologic and rheumatologic manifestations and sometimes overlaps with plaque psoriasis. Pustular palmoplantar psoriasis (PPP) affects the palmar and plantar areas of the skin, while generalized pustular psoriasis (GPP) can affect large areas of skin and tends to be more severe, even life threatening. PPP can accompany psoriatic arthritis or can be a side effect of tumor necrosis factor (TNF) inhibitor therapy, or a non–drug-induced component of rheumatologic syndromes, according to Kristina Callis Duffin, MD, an associate professor and chair of dermatology at the University of Utah, Salt Lake City.

“Each phenotype could be considered an orphan disease, and the response to therapy is often unpredictable,” Dr. Duffin said during a session on pustular psoriasis at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

But there is some positive news. A study in 2011 of several people with GPP opened the door to better understanding the pathophysiology of pustular psoriasis. Researchers identified a causal autosomal mutation in the IL36RN gene, which encodes an antagonist to the interleukin-36 receptor (Am J Hum Genet. 2011 Sep 9;89[3]:432-7). “As a result of this paper and others, drug development in this space has recently accelerated,” Dr. Duffin said.

In fact, she added,“it’s my opinion that pustular psoriasis is now where plaque psoriasis was 20 years ago, when accelerated drug development was driving a better understanding of the pathogenesis of psoriatic disease and its comorbidities, and also driving outcome measure development.”

In another presentation at the meeting, Hervé Bachelez, MD, PhD, professor of dermatology and immunologist at the University of Paris and Saint-Louis Hospital, Paris, discussed recent advances in drug development for pustular psoriasis. He noted other recent findings of genetic variants related to the disease, including AP1S3, CARD14, and SERPINA3.

For GPP, he said, the current algorithm for management is based on weak evidence for treatments like acitretin, cyclosporine, methotrexate, and infliximab. The story is similar for other biologics, with evidence in the form of case series; open-label studies; controlled, prospective studies; or retrospective analyses. Most of the evidence has been amassed for TNF inhibitors. A retrospective study of all TNF inhibitors suggested they may be effective as induction and maintenance therapy, he noted.

Among IL-17A inhibitors, a prospective study of 12 patients in Japan found secukinumab showed efficacy against GPP, as did studies of ixekizumab and brodalumab. A small phase 3 study in Japan demonstrated efficacy for the IL-23 inhibitor guselkumab in patients with erythrodermic psoriasis and GPP (J Dermatol. 2018 May;45[5]:529-39).

The limited data are a reflection in part of the difficulty in studying GPP, since its flares tend to be more self-remitting than with psoriasis vulgaris or PPP.

There are two monoclonal antibodies against the IL-36 receptor currently being developed. A proof-of-concept study of one of them, spesolimab, showed promise against GPP, with five of seven patients reaching “clear” or “almost clear” scores on the Generalized Pustular Psoriasis Physician Global Assessment within a week after infusion and in all seven by the fourth week (N Engl J Med. 2019 Mar 7;380[10]:981-3).

With respect to PPP, the strongest evidence for conventional therapies comes from two randomized, controlled trials of cyclosporine, with response rates of 48% and 89%, compared with 19% and 21%, respectively, in the placebo groups, although the primary endpoint was poorly designed, according to Dr. Bachelez. Retinoids like etretinate and acitretin, combined with psoralen and UVA, also have some supporting evidence regarding efficacy.

Among biologics, secukinumab did not fare well in a phase 3 study of patients with PPP. A subset of patients may benefit from it, but there are no biomarkers available to identify them, Dr. Bachelez said. A phase 2 study of guselkumab in Japan told a similar story, with only weak signs of efficacy. While there are many more ongoing clinical trials evaluating treatments for PPP, which is encouraging, PPP seems to be more challenging at this stage to tackle than GPP, Dr. Bachelez added. “The genetically inherited IL-36 antagonist abnormalities are clearly driving the advances regarding the pathogenesis of the disease, mainly for GPP rather than PPP.”

Part of the efforts to develop therapies for pustular psoriasis relies on the development of new outcome measures, or adaptation of existing ones. “We have a need to adapt or develop new investigator-reported measures, we need to adapt or develop new patient-reported outcomes,” Dr. Duffin said.

Many existing measures use inconsistent language and anchoring definitions, and some may be proprietary, she added. “The language varies by sponsor and is sometimes tweaked or modified by the agencies. Often synonyms are being used … it raises questions, does it change the validity of the instrument?”

Dr. Duffin called for the research community to use the pause in clinical research during the COVID-19 pandemic to reassess the research agenda, develop consensus on performing and training for GPP and PPP assessments, develop patient-reported outcomes, and strengthen connections to industry.

Dr. Duffin and Dr. Bachelez have consulted, served on the advisory board, been a speaker for, and/or received research support from a wide range of pharmaceutical companies, including those that manufacture and develop psoriasis treatments.
 

Pustular psoriasis is a rare condition that presents significant challenges to clinicians, not least because it comes in varied forms that are not well understood.

It has various dermatologic and rheumatologic manifestations and sometimes overlaps with plaque psoriasis. Pustular palmoplantar psoriasis (PPP) affects the palmar and plantar areas of the skin, while generalized pustular psoriasis (GPP) can affect large areas of skin and tends to be more severe, even life threatening. PPP can accompany psoriatic arthritis or can be a side effect of tumor necrosis factor (TNF) inhibitor therapy, or a non–drug-induced component of rheumatologic syndromes, according to Kristina Callis Duffin, MD, an associate professor and chair of dermatology at the University of Utah, Salt Lake City.

“Each phenotype could be considered an orphan disease, and the response to therapy is often unpredictable,” Dr. Duffin said during a session on pustular psoriasis at the virtual annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.

But there is some positive news. A study in 2011 of several people with GPP opened the door to better understanding the pathophysiology of pustular psoriasis. Researchers identified a causal autosomal mutation in the IL36RN gene, which encodes an antagonist to the interleukin-36 receptor (Am J Hum Genet. 2011 Sep 9;89[3]:432-7). “As a result of this paper and others, drug development in this space has recently accelerated,” Dr. Duffin said.

In fact, she added,“it’s my opinion that pustular psoriasis is now where plaque psoriasis was 20 years ago, when accelerated drug development was driving a better understanding of the pathogenesis of psoriatic disease and its comorbidities, and also driving outcome measure development.”

In another presentation at the meeting, Hervé Bachelez, MD, PhD, professor of dermatology and immunologist at the University of Paris and Saint-Louis Hospital, Paris, discussed recent advances in drug development for pustular psoriasis. He noted other recent findings of genetic variants related to the disease, including AP1S3, CARD14, and SERPINA3.

For GPP, he said, the current algorithm for management is based on weak evidence for treatments like acitretin, cyclosporine, methotrexate, and infliximab. The story is similar for other biologics, with evidence in the form of case series; open-label studies; controlled, prospective studies; or retrospective analyses. Most of the evidence has been amassed for TNF inhibitors. A retrospective study of all TNF inhibitors suggested they may be effective as induction and maintenance therapy, he noted.

Among IL-17A inhibitors, a prospective study of 12 patients in Japan found secukinumab showed efficacy against GPP, as did studies of ixekizumab and brodalumab. A small phase 3 study in Japan demonstrated efficacy for the IL-23 inhibitor guselkumab in patients with erythrodermic psoriasis and GPP (J Dermatol. 2018 May;45[5]:529-39).

The limited data are a reflection in part of the difficulty in studying GPP, since its flares tend to be more self-remitting than with psoriasis vulgaris or PPP.

There are two monoclonal antibodies against the IL-36 receptor currently being developed. A proof-of-concept study of one of them, spesolimab, showed promise against GPP, with five of seven patients reaching “clear” or “almost clear” scores on the Generalized Pustular Psoriasis Physician Global Assessment within a week after infusion and in all seven by the fourth week (N Engl J Med. 2019 Mar 7;380[10]:981-3).

With respect to PPP, the strongest evidence for conventional therapies comes from two randomized, controlled trials of cyclosporine, with response rates of 48% and 89%, compared with 19% and 21%, respectively, in the placebo groups, although the primary endpoint was poorly designed, according to Dr. Bachelez. Retinoids like etretinate and acitretin, combined with psoralen and UVA, also have some supporting evidence regarding efficacy.

Among biologics, secukinumab did not fare well in a phase 3 study of patients with PPP. A subset of patients may benefit from it, but there are no biomarkers available to identify them, Dr. Bachelez said. A phase 2 study of guselkumab in Japan told a similar story, with only weak signs of efficacy. While there are many more ongoing clinical trials evaluating treatments for PPP, which is encouraging, PPP seems to be more challenging at this stage to tackle than GPP, Dr. Bachelez added. “The genetically inherited IL-36 antagonist abnormalities are clearly driving the advances regarding the pathogenesis of the disease, mainly for GPP rather than PPP.”

Part of the efforts to develop therapies for pustular psoriasis relies on the development of new outcome measures, or adaptation of existing ones. “We have a need to adapt or develop new investigator-reported measures, we need to adapt or develop new patient-reported outcomes,” Dr. Duffin said.

Many existing measures use inconsistent language and anchoring definitions, and some may be proprietary, she added. “The language varies by sponsor and is sometimes tweaked or modified by the agencies. Often synonyms are being used … it raises questions, does it change the validity of the instrument?”

Dr. Duffin called for the research community to use the pause in clinical research during the COVID-19 pandemic to reassess the research agenda, develop consensus on performing and training for GPP and PPP assessments, develop patient-reported outcomes, and strengthen connections to industry.

Dr. Duffin and Dr. Bachelez have consulted, served on the advisory board, been a speaker for, and/or received research support from a wide range of pharmaceutical companies, including those that manufacture and develop psoriasis treatments.