Vaccination recommendations for adults receiving biologics and oral therapies for psoriasis and psoriatic arthritis: Delphi consensus from the medical board of the National Psoriasis Foundation.

BACKGROUND: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. OBJECTIVE: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. METHODS: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. RESULTS: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. LIMITATIONS: Studies regarding infection rates after vaccination are lacking. CONCLUSION: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.

Methotrexate for inflammatory skin disease in pediatric patients: Consensus treatment guidelines.

Methotrexate (MTX) is a readily accessible drug, first used in 1948 and employed for a wide variety of indications since then. However, despite widespread off-label use, FDA labeling does not include approved indications for the use of MTX for many inflammatory skin diseases in pediatric patients, including morphea, psoriasis, atopic dermatitis, and alopecia areata, among others. Without published treatment guidelines, some clinicians may be hesitant to use MTX off-label, or uncomfortable prescribing MTX in this population. To address this unmet need, an expert consensus committee was convened to develop evidence- and consensus-based guidelines for use of MTX to treat pediatric inflammatory skin disease. Clinicians with experience and expertise in clinical research, drug development, and treating inflammatory skin disease in pediatric patients with MTX were recruited. Five committees were created based on major topic areas: (1) indications and contraindications, (2) dosing, (3) interactions with immunizations and medications, (4) adverse effects (potential for and management of), and (5) monitoring needs. Pertinent questions were generated and addressed by the relevant committee. The entire group participated in a modified Delphi process to establish agreement on recommendations for each question. The committee developed 46 evidence- and consensus-based recommendations, each with >70% agreement among members, across all five topics. These are presented in tables and text, along with a discussion of supporting literature, and level of evidence. These evidence- and consensus-based recommendations will support safe and effective use of MTX for the underserved population of pediatric patients who may benefit from this valuable, time-honored medication.

Cardiometabolic multimorbidity is common among patients with psoriasis and is associated with poorer outcomes compared to those without comorbidity.

BACKGROUND: Associations between cardiometabolic multimorbidity and response to therapy in psoriasis are unknown. OBJECTIVE: Determine the associations of multimorbidity with response to biologic treatment in psoriasis patients. METHODS: CorEvitas Psoriasis Registry participants who initiated biologic therapy and had 6-month follow-up were stratified by 0, 1, 2+ comorbidities (diabetes, hypertension, hyperlipidemia). Adjusted odds ratios (95% CIs) were calculated overall and separately by biologic class (TNFi, IL-17i, IL-12/23i + IL-23i), to assess the likelihood of achieving response for the 1 and 2+ groups vs. 0. RESULTS: Of 2,923 patients, 49.5%, 24.7% and 25.8% reported 0, 1 and 2+ comorbidities, respectively. Overall, likelihood of PASI75 was 18% (OR = 0.82; 95%CI: 0.67, 1.00) and 23% (OR = 0.77; 95%CI: 0.63, 0.96) lower in those with 1 and 2+ comorbidities, respectively, vs. 0. In those who initiated IL-17i, odds of PASI75 and PAS90 were 34% (OR = 0.66; 95%CI: 0.48-0.91) and 35% (OR = 0.65; 95%CI: 0.47-0.91) lower in the 2+ multimorbidity cohort. No significant associations were found among users of TNFi or IL-12/23i + IL-23i groups in the multimorbidity group. LIMITATIONS: Patients may not be representative of all psoriasis patients. CONCLUSION: Multimorbidity in psoriasis may decrease the likelihood of achieving treatment response to biologic therapy and should be considered when discussing treatment expectations with patients.

Cardiac and Sudomotor Autonomic Function in Subjects with Psoriasis With and Without Metabolic Syndrome.

Purpose: Studies have shown that subjects with psoriasis (PsO) are associated with an increased risk of developing metabolic syndrome (MetS), diabetes, and cardiovascular disease. In addition, MetS and diabetes are associated with autonomic dysfunction (AD). The aim of this study was to investigate cardiac and sudomotor autonomic function in subjects with PsO and without diabetes. Methods: A cross-sectional study was performed in 20 subjects with PsO, compared with age- and sex-matched 21 healthy controls, and 20 subjects with MetS. Subjects underwent skin evaluation by dermatologist, glycated hemoglobin (HbA1c), insulin, glucose, and lipid levels, sudomotor function testing with Sudoscan™ device (Impeto Medical, Paris, France), and cardiac autonomic function testing with ANSAR device (ANX 3.0; ANSAR Group, Inc., Philadelphia, PA). Quality of Life (QOL) and peripheral neurologic function were also assessed. Results: Participants with PsO were significantly more obese, had higher levels of fasting insulin and triglycerides, and were more insulin resistant when compared to controls. Subjects with PsO showed significantly worse cardiac autonomic function when compared to control and MetS groups. Sudomotor function and QOL scores were similar between the groups. Subgroup analysis of PsO subjects without MetS criteria (n = 15) showed persistent significantly deteriorated cardiac autonomic function when compared to the other two groups. Conclusion: This study suggests an association between PsO and cardiac AD, independent of the presence of overt dysglycemia and MetS. Additional larger studies are needed to clarify the significance of these findings and the relationship between PsO, AD, and metabolic disease.

Comorbid obesity and history of diabetes are independently associated with poorer treatment response to biologics at 6 months: A prospective analysis in Corrona Psoriasis Registry.

BACKGROUND: Psoriasis is associated with comorbid systemic metabolic disease. OBJECTIVE: To assess possible associations of comorbid obesity, history of diabetes, hypertension, and hyperlipidemia with response to biologic treatment at 6 months among patients in CorEvitas' Psoriasis Registry. METHODS: Participants included 2924 patients initiating biologic therapy (tumour necrosis factor inhibitors [TNFi], interleukin [IL]-17i, IL-12/23i, or IL-23i) with baseline and 6-month follow-up visits available. Logistic regressions resulted in adjusted odd ratios (OR) and 95% confidence intervals (CI) for achievement of response in select outcomes for those with obesity and history of diabetes, hypertension, and hyperlipidemia relative to those without each. RESULTS: Overall, obesity reduced by 25% to 30% odds of achieving PASI75 (OR, 0.75; 95% CI, 0.64-0.88) and PASI90 (OR, 0.70; 95% CI, 0.59-0.81). History of diabetes reduced odds of achieving PASI75 by 31% (OR, 0.69; 95% CI, 0.56-0.85) and PASI90 by 21% (OR, 0.79; 95% CI, 0.63-0.98). Obesity was associated with lower response to TNFi and IL-17i classes. Independent of obesity, diabetes was associated with poorer outcomes when on IL-17i therapy and hypertension, to a lesser extent, when on the TNFi class. No significant associations were found in the hyperlipidemia group. LIMITATIONS: The study assessed only short-term effectiveness and small sample sizes limited the power to detect differences. CONCLUSION: Assessment of comorbid disease burden is important for improved likelihoods of achieving treatment response with biologics.

Demographics, Disease Characteristics, and Patient-Reported Outcomes Among Patients with Psoriasis Who Initiated Guselkumab in CorEvitas' Psoriasis Registry.

INTRODUCTION: Guselkumab is approved for the treatment of both moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA) in the USA. However, little is known about patients initiating guselkumab in a real-world setting. The objective of this study was to describe baseline characteristics among patients with plaque psoriasis who initiated guselkumab at or after enrollment in CorEvitas' Psoriasis Registry. METHODS: Adult patients who initiated guselkumab in the Psoriasis Registry between July 18, 2017 and November 6, 2018 were included. Demographics, disease characteristics, and patient-reported outcome measures (PROMs) were assessed at the time of guselkumab initiation (baseline). Patients with psoriasis were stratified according to the number of previously received biologics (0 to 4+) for comparison. A subset of patients with psoriasis and concomitant dermatologist-diagnosed PsA were stratified into biologic-naïve and biologic-experienced groups. RESULTS: Among 687 patients with psoriasis who initiated guselkumab, biologic-naïve patients and those with four or more prior biologics had the most severe disease and the worst PROM scores at baseline. Among 251 patients with concomitant dermatologist-diagnosed PsA, biologic-naïve patients had more severe disease and worse PROM scores than biologic-experienced patients. CONCLUSIONS: These findings highlight important differences in baseline characteristics according to biologic experience among patients with plaque psoriasis with or without concomitant PsA initiating guselkumab in a real-world setting.

Psoriasis Severity, Comorbidities, and Treatment Response Differ among Geographic Regions in the United States.

Little is known about how psoriatic disease characteristics and treatment outcomes differ geographically in the United States. Our aim was to explore real-world, geographic variations in the use of biologic classes and outcomes within the Corrona Psoriasis Registry. Patient demographics and disease characteristics were assessed at biologic initiation and at 6 months. Logistic regressions were conducted to evaluate the odds of achieving targeted outcomes for seven United States geographic regions. We examined 737 biologic initiations among 717 patients. IL-17 inhibitors were used most frequently (45%), followed by IL-12‒IL-23 and IL-23 inhibitors (38%) and TNF inhibitors (17%). The proportions of patients with obesity (body mass index > 30) and very severe psoriasis (body surface area > 20) were greatest in the East South Central and West South Central regions. After adjusting for age, sex, race, body mass index, and baseline body surface area, decreased odds of achieving 75% improvement in PASI at 6 months were observed among patients in the East South Central (OR = 0.47, 95% confidence interval = 0.28-0.79, P = 0.004), West South Central (OR = 0.43, 95% confidence interval = 0.22-0.87, P = 0.019), and Pacific (OR = 0.49, 95% confidence interval = 0.28-0.84, P = 0.010) regions compared with those observed among patients in the Northeast. The East South Central and West South Central regions may have the greatest frequencies of very severe disease burden and, along with the Pacific region, may be less likely to achieve targeted response within 6 months of initiating biologic therapy.

Pustular Psoriasis: A Narrative Review of Recent Developments in Pathophysiology and Therapeutic Options.

Pustular psoriasis is an unusual form of psoriasis that frequently presents clinical challenges for dermatologists. The condition presents with pustules on an erythematous background and has two distinct subtypes: localized disease on the palms and soles, called palmoplantar pustulosis (PPP), and generalized pustular psoriasis (GPP). The involvement of the fingers, toes, and nails is defined as a separate localized variant, acrodermatitis continua of Hallopeau, and is now thought to be a subset of PPP. The rarity of pustular psoriasis frequently makes the correct diagnosis problematic. In addition, treatment is limited by a relative lack of evidence-based therapeutic options. Current management is often based on existing therapies for standard plaque psoriasis. However, there remains a need for treatments with high, sustained efficacy and a rapid onset of action in pustular psoriasis. Recent advances in understanding of the pathogenesis of pustular psoriasis have provided insights into potential therapies. Treatment of pustular psoriasis is generally determined by the extent and severity of disease, and recent years have seen an increasing use of newer agents, including biologic therapies. Current classes of biologic therapies with US Food and Drug Administration and European Medicines Agency approval for treatment of moderate-to-severe plaque psoriasis in the USA (and elsewhere) include tumor necrosis factor alpha inhibitors (adalimumab, certolizumab pegol, etanercept, infliximab), interleukin (IL)-17 inhibitors (brodalumab, ixekizumab, secukinumab), an IL-12/23 inhibitor (ustekinumab), and IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab). Recently, specific inhibitors of the IL-36 pathway have been evaluated in GPP and PPP, including spesolimab, an IL-36 receptor inhibitor which has shown promising results in GPP. The emerging drugs for pustular psoriasis offer the possibility of rapid and effective treatment with lower toxicities than existing therapies. Further research into agents acting on the IL-36 pathway and other targeted therapies has the potential to transform the future treatment of patients with pustular psoriasis. This article reviews the clinical features of PPP and GPP, and current understanding of the genetics and immunopathology of these conditions; it also provides an update on emerging treatments.

Pustular psoriasis is a skin condition where people develop small pus-filled blisters on their skin. Pustular psoriasis may affect certain areas of the body, such as the palms and/or the soles. This is called palmoplantar pustulosis (PPP for short). Another type of pustular psoriasis can affect most of the body called generalized pustular psoriasis (GPP for short). Not many people have PPP or GPP. Around 5­12 in every 10,000 people worldwide develop PPP. GPP is even rarer, affecting only 2­7 out of every 1 million people. In addition to being relatively uncommon, these conditions are challenging to treat. This article aims to help doctors who treat skin conditions (dermatologists) to identify and treat people with pustular psoriasis. Currently there is no standard treatment for GPP and PPP in the USA or Europe, but several medicines are approved for treatment of GPP in Japan. Doctors often use treatments that have been shown to work in plaque psoriasis, which is the most common type of psoriasis, to treat people with GPP and PPP. Traditional treatments for PPP and GPP are often not effective. Researchers are working on developing new effective treatments for pustular psoriasis that may work more rapidly and have fewer side effects. These are expected to be available in the next few years.

National Psoriasis Foundation COVID-19 Task Force guidance for management of psoriatic disease during the pandemic: Version 2-Advances in psoriatic disease management, COVID-19 vaccines, and COVID-19 treatments.

OBJECTIVE: To update guidance regarding the management of psoriatic disease during the COVID-19 pandemic. STUDY DESIGN: The task force (TF) includes 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation staff. Clinical questions relevant to the psoriatic disease community were informed by inquiries received by the National Psoriasis Foundation. A Delphi process was conducted. RESULTS: The TF updated evidence for the original 22 statements and added 5 new recommendations. The average of the votes was within the category of agreement for all statements, 13 with high consensus and 14 with moderate consensus. LIMITATIONS: The evidence behind many guidance statements is variable in quality and/or quantity. CONCLUSIONS: These statements provide guidance for the treatment of patients with psoriatic disease on topics including how the disease and its treatments affect COVID-19 risk, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 (including novel vaccination), and what they should do if they develop COVID-19. The guidance is a living document that is continuously updated by the TF as data emerge.

Characterization of insufficient responders to ustekinumab in patients with moderate-to-severe psoriasis in the US Corrona Psoriasis Registry.

OBJECTIVE: Biologic therapies have revolutionized the management of moderate-to-severe psoriasis; however, there are a limited number of US real-world studies characterizing patients based on response to these treatments. This study examined characteristics at enrollment and change in outcomes of US patients with moderate-to-severe psoriasis who achieved insufficient responses with ustekinumab. METHODS: This study included patients enrolled in the Corrona Psoriasis Registry from April 2015 to June 2018 who initiated ustekinumab at enrollment and who were stratified based on achievement of psoriasis body surface area improving to <3% or by 75% from enrollment to the 6-month follow-up visit (response vs insufficient response). Patient demographics and disease characteristics were described at enrollment, and changes in outcomes were assessed at 6-month follow-up for ustekinumab responders and insufficient responders. RESULTS: Of the 178 patients who initiated ustekinumab in the Corrona Psoriasis Registry and had ≥1 follow-up visit, 99 (55.6%) were classified as responders at the 6-month follow-up visit. Logistic regression modeling showed that increasing age was significantly associated with a decreased likelihood of achieving a response (OR, 0.981 [95%CI, 0.962-0.999]; p = .049). CONCLUSIONS: These findings may help dermatologists characterize patients with moderate-to-severe psoriasis who have inadequate responses to biologic treatments.

Achievement of the National Psoriasis Foundation treatment targets with ixekizumab: Pooled analyses from 4 clinical studies.

BACKGROUND: The National Psoriasis Foundation (NPF) published treatment targets for US patients with plaque psoriasis. However, data are lacking on how well existing therapies help achieve these goals. OBJECTIVE: To examine the ability of an interleukin 17 inhibitor, ixekizumab, in achieving these treatment targets. METHODS: Post hoc analysis was performed on pooled data from 4 phase III clinical trials assessing ixekizumab for plaque psoriasis: the UNCOVER-1, -2, and -3 trials and the IXORA-S trial. Treatment response was evaluated using the NPF-defined acceptable response (affected body surface area [BSA] of 3% or less or BSA improvement of 75% or higher at 12 weeks of treatment) and target response (BSA of 1% or less at 12 weeks and every 6 months thereafter). RESULTS: In the UNCOVER trials (n = 2701), acceptable and target response rates at week 12 were 73.9% and 51.8% with ixekizumab 80 mg every 2 weeks, 35.7% and 14.9% with etanercept 50 mg, and 3.0% and 0.6% with placebo, respectively. In the IXORA-S trial (n = 302), acceptable and target response rates at week 12 were significantly higher with ixekizumab every 2 weeks versus ustekinumab (acceptable response 68.4% vs 38.6%, P < .0001; target response 50.7% vs 24.1%, P < .0001). LIMITATIONS: Data were from controlled studies and may not reflect real-world practice. CONCLUSION: The majority of patients treated with ixekizumab in 4 phase III clinical trials achieved NPF, patient-centered treatment targets.

Characterization of insufficient responders to anti-tumor necrosis factor therapies in patients with moderate to severe psoriasis: real-world data from the US Corrona Psoriasis Registry.

OBJECTIVE: Biologic therapies have dramatically changed the management of moderate to severe psoriasis; however, few US real-world studies characterize the unmet needs of patients who do not respond to biologic therapies. This study examined the characteristics at enrollment of patients with moderate to severe psoriasis who had insufficient responses to anti-tumor necrosis factor therapies (anti-TNFs). METHODS: Patients enrolled in the Corrona Psoriasis Registry from April 2015 to June 2018 who initiated an anti-TNF at enrollment were stratified on the basis of body surface area (BSA) improvement to <3% or a 75% improvement from enrollment to the 6-month follow-up visit (response versus insufficient response). Patient demographics and disease characteristics were described at enrollment, and changes in outcomes were assessed at 6-month follow-up for those who received anti-TNFs. RESULTS: Of 180 anti-TNF initiators who had ≥1 follow-up visit, 50.6% were classified as responders. Logistic regression modeling showed that female sex was significantly associated with a decreased likelihood of achieving a response (OR = 0.534, 95% CI = 0.289-0.988, p = .046). CONCLUSION: Despite the small sample size and short follow-up period, these findings may help dermatologists to identify patients with moderate to severe psoriasis who have unmet treatment needs.