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Background: Registry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID-19) outcomes compared with patients receiving no systemic treatments., Objectives: We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation., Methods: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk-mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed-effects model., Results: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk-mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35-1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23-1·56). Shielding was associated with established risk factors for severe COVID-19 [male sex (OR 1·14, 95% CI 1·05-1·24), obesity (OR 1·37, 95% CI 1·23-1·54), comorbidity burden (OR 1·43, 95% CI 1·15-1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27-1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36-1·80). Modest differences in the proportion shielding were observed across nations., Conclusions: Greater risk-mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID-19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence-based patient communication on risk-mitigation strategies and may help inform updated public health guidelines as the pandemic continues., (© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Pustular psoriasis (PsO) is an uncommon variant of PsO that may present in a generalized or localized fashion with or without musculoskeletal or systemic inflammatory involvement.Generalized pustular PsO (GPP) presents as a widespread acute or subacute pustular eruption that may be familial and is often associated with severe flares and systemic inflammation. The palmoplantar pustulosis variant is localized to palms and soles, whereas acrodermatitis continua of Hallopeau is localized to the nail apparatus. Patients with pustular PsO may have overlapping plaque PsO and may develop psoriatic arthritis (PsA). Pustulosis is also a feature of both synovitis, acne, pustulosis, hyperostosis, osteomyelitis (SAPHO) syndrome and chronic non-bacterial osteomyelitis. At the 2020 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, members were given an overview of the cutaneous features of pustular PsO, SAPHO, and recent insights into the genetics of GPP, leading to new targeted drug therapies and the development of validated endpoints., (Copyright © 2021 by The Journal of Rheumatology.)

Competing Interests: None disclosed.

Background: In 2018 in France, overall mean health-related out-of-pocket (OOP) expenditures were 214.00€/year/patient., Aim: To evaluate OOP expenditures for psoriasis patients in France., Methodology: Observational, cross-sectional, non-comparative, multicentre study in 3000 patients with clinically confirmed psoriasis who responded to a specific digital questionnaire collecting demographic and socio-economic characteristics, assessing the 3 domains (severity, psychosocial impact and past history and interventions) of the patient's Simplified Psoriasis Index (sa-SPI) and expenditures to manage psoriasis, including OOP. Multivariate linear regression was conducted to search for factors associated with higher OOP., Results: In total, 2681 patients completed the questionnaire and, of those, 2562 provided clinically validated data. Overall, 60% were women; the mean age was 49.4 ± 14.8 years. 30% of the patients declared that they suffered from psoriatic arthritis. The final mean sa-SPI core was 10.86 ± 9.70. Of these 2562 patients, 243 (9.5%) had severe, 442 (17.3%) moderate and 1877 (73.3%) mild psoriasis. In addition, 932 (36.4%) patients reported facial involvement, 724 (28.25%) genital impairment and 1124 (43.8%) lesions on the limbs. Mean OOP expenditures to manage psoriasis per patient were 531.00€, 439.74€ ± 939.85€ for patients with mild, 791.06€ ± 1367.67€ with moderate and 1077.64€ ± 1680.14€ for patients with severe psoriasis. For patients with psoriasis in the genital area, the median amount of expenditures (251.17€; CI95% [138.35;363.99]) was significantly higher than that for the face (183.85€; CI95% [78.76;288.94]) or limbs (199.96€; CI95% [93.77;306.15); (P < 0.001). More than 90% of the patients had OOP expenditures for over-the-counter products (97.5%) and alternative care (92.0%), especially for emollients and/or hydrating products., Conclusion: In France, in 2019, OOP expenditures to manage psoriasis were on average more than twice as high as the overall mean health-related OOP expenditures estimated by the French Health Agency in 2018. These results should lead health authorities to review certain standards of healthcare reimbursement., (© 2020 European Academy of Dermatology and Venereology.)

Introduction: Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterised by recurrent flares of widespread neutrophilic aseptic skin pustular eruption. Despite the availability of approved biologics for GPP in Japan, Taiwan and Thailand, associated evidence is largely based on uncontrolled studies in which acute flares were not directly assessed. Therefore, there is a high unmet need to investigate new rapid-acting effective treatments that resolve symptoms associated with acute GPP flares. A prior Phase I proof-of-concept study showed rapid improvements in skin and pustule clearance with a single intravenous dose of spesolimab, a novel anti-interleukin-36 receptor antibody, in patients presenting with an acute GPP flare. Here, we present the design and rationale of Effisayil 1, a global, Phase II, placebo-controlled study to evaluate the efficacy, safety and tolerability of spesolimab in patients presenting with an acute GPP flare., Methods and Analysis: At least 51 patients with an acute GPP flare will be randomised 2:1 to receive a single 900 mg intravenous dose of spesolimab or placebo and followed for up to 28 weeks. The primary endpoint is a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (pustule clearance) at Week 1. The key secondary endpoint is a GPPGA score of 0 or 1 (clear or almost clear) at Week 1. Safety will be assessed over the study duration by the occurrence of treatment-emergent adverse events. Blood and skin biopsies will be collected to assess biomarkers. Superiority of spesolimab over placebo in the proportion of patients achieving the primary and key secondary endpoints will be evaluated., Ethics and Dissemination: The study complies with the ethical principles of the Declaration of Helsinki, the International Council for Harmonisation's Good Clinical Practice and local regulations. Ethics committee approvals have been obtained for each centre from all participating countries and are listed in online supplementary file 1. Primary results will be published in a peer-reviewed journal., Trial Registration Details: ClinicalTrials.gov identifier: NCT03782792; Pre-results., Competing Interests: Competing interests: SR is an employee of Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, USA. HD is an employee of Boehringer Ingelheim Investment Co Ltd, Shanghai, China. KT is an employee of Boehringer Ingelheim GmbH, Ingelheim, Germany. CT is an employee of Boehringer Ingelheim International GmbH, Biberach, Germany. SEC declares paid activities as advisor, speaker or consultant for AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Leo Pharma, MSD, Novartis, Pfizer, Sanofi and UCB. MGL declares paid consulting activities for Aditum Bio, Allergan, Almirall, Arcutis, Inc, Avotres Therapeutics, BirchBioMed Inc, BMD skincare, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Facilitate International Dermatologic Education, Foundation for Research and Education in Dermatology, Inozyme Pharma, Kyowa Kirin, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, NeuroDerm, Pfizer, Promius (Dr Reddy’s Laboratories Ltd), Serono, Theravance and Verrica, and research funds from AbbVie, Amgen, Arcutis, Boehringer Ingelheim, Dermavant, Eli Lilly, Incyte, Janssen Research & Development, LLC, LEO Pharma, Ortho Dermatologics, Pfizer and UCB. SM and HT declare paid consulting activities for Boehringer Ingelheim. ADB declares paid consulting activities for AbbVie, Almirall, Boehringer Ingelheim, Celgene, Janssen, LEO Pharma, Lilly, Novartis and UCB. TFT declares conducting clinical trials or paid consulting activities for AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Merck Sharp & Dohme, Novartis International, Pfizer and UCB Pharma. AM declares receiving research grants, consulting fees and/or speaker’s fees from AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Eisai, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nichi-Iko, Nippon Kayaku, Novartis, Sun Pharmaceutical Industries, Taiho Pharmaceutical and Torii Pharmaceutical and Ushio. AAN declares being a consultant and advisor and/or receiving speaking fees and/or grants and/or served as an investigator in clinical trials for AbbVie, Almirall, Amgen, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, GSK, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Sandoz, Sanofi, Serono and UCB. MZ declares receiving grants, consulting fees, and/or speaker’s fees from AbbVie, Boehringer Ingelheim, Janssen-Cilag, LEO Pharma China, Novartis, Pfizer Inc and Xian-Janssen. JX declares receiving grants, consulting fees, and/or speaker’s fees from AbbVie, Boehringer Ingelheim, Novartis, Pfizer Inc and Sanofi. HB declares paid consulting activities for AbbVie, Almirall, BIOCAD, Boehringer Ingelheim, Celgene, Janssen, Kyowa-Kirin, LEO Pharma, Lilly, Mylan, Novartis and UCB, and grant support from Boehringer Ingelheim, Janssen, LEO Pharma, Novartis and Pfizer., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Pustular psoriasis (PsO) is an uncommon variant of PsO that may present in a generalized or localized fashion with or without musculoskeletal or systemic inflammatory involvement. Generalized pustular PsO (GPP) presents as a widespread acute or subacute pustular eruption that may be familial and is often associated with severe flares and systemic inflammation. The palmoplantar pustulosis variant is localized to palms and soles, whereas acrodermatitis continua of Hallopeau is localized to the nail apparatus. Patients with pustular PsO may have overlapping plaque PsO and may develop psoriatic arthritis (PsA). Pustulosis is also a feature of both synovitis, acne, pustulosis, hyperostosis, osteomyelitis (SAPHO) syndrome and chronic nonbacterial osteomyelitis. At the 2020 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) annual meeting, members were given an overview of the cutaneous features of pustular PsO, SAPHO, and recent insights into the genetics of GPP, leading to new targeted drug therapies and the development of validated endpoints.

Background: Obesity is associated with an increased risk of psoriasis., Objective: In this study, we examined whether body mass index (BMI) is taken into account when choosing first-line biologic therapy for psoriasis., Methods: In this cohort study, we compared obese (BMI ≥30 kg/m2) and non-obese patients for the first-line biologic therapy prescribed, its survival, reasons for discontinuation, therapy optimization, co-prescription of methotrexate and factors associated with long drug survival., Results: A total of 931 patients were included: 594 (64%) were male, median age was 46 years (interquartile range 36-56). The most-prescribed biologic agents as first-line treatment were adalimumab (ADA; 42.7%), ustekinumab (UST; 29.9%) and etanercept (ETA; 22.9%); only frequency of infliximab (IFX) prescription differed between groups. Drug survival was significantly shorter for obese than non-obese patients (p < 2.10-4) and was worse for obese than non-obese patients for UST (p = 0.009) and ETA (p = 0.02), with no difference for ADA (p = 0.11). The main reason for discontinuation was primary inefficacy (62%), which was more frequent in obese than non-obese patients. The cumulative incidence of optimization did not significantly differ between the groups, except for ADA (SHR 1.91, 95% CI [1.23-2.96], p = 0.005). On multivariate analysis, risk of discontinuation was associated with only ETA as first-line biologic therapy (HR 1.51, 95% CI 1.04-2.19)., Conclusion: This study highlighted the lack of difference in prescription of first-line biologic treatment, except for IFX, between obese and non-obese patients presenting moderate-to-severe psoriasis. Drug survival in obese patients is shorter, mainly because of inefficacy, than in non-obese patients. This highlights the need for targeted pharmacological studies in obese individuals to find optimal administration schemes., (© 2021 S. Karger AG, Basel.)

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition substantially impacting patients' quality of life; the pathogenesis remains unclear, and treatment is complex and not yet standardized. Observational data are increasingly being used to evaluate therapeutics in "real-life" interventions, and the development of e-cohorts is offering new tools for epidemiological studies at the population level., Objective: The aim of this study was to describe the clinical characteristics and treatment history of HS participants in the Community of Patients for Research (ComPaRe) cohort and to compare these to other cohorts., Methods: We performed a cross-sectional study of the baseline data of HS participants in ComPaRe, an e-cohort of patients with chronic diseases. Data were collected using patient-reported questionnaires about clinical-dem-ographic aspects, quality of life, and treatment history., Results: A total of 396 participants (339 females, 57 males) were included (mean age 38 years); 83 (21%) had a family history of HS, 227 (57.3%) were current smokers, and 241 (60.9%) were overweight or obese. Most of the participants declared a Hurley stage II (n = 263, 66.4%) or III (n = 76, 20.3%). The breast was more frequently affected in women than men (37.5 vs. 5.3%, p < 0.0001), whereas the dorsal region was more frequently affected in men (39.5 vs. 10.9%, p < 0.0001). Increased disease stage was associated with obesity (25.9 vs. 33.8 vs. 51.3%, p = 0.02) and some HS localizations (genital [p < 0.005], pubis [p < 0.007], gluteal fold [p = 0.02], and groin [p < 0.0001]). The most frequently prescribed treatments were oral antibiotics (n = 362, 91.4%), especially amoxicillin-clavulanic acid and cyclins. Less than 10% of participants received biologics. Most of these results were consistent with previously published cohorts., Conclusion: Recruitment of participants by such a web platform can be a faster way to get relevant scientific data for a wide variety of patients that could be used for epidemiological studies and to evaluate therapeutics in "real-life" interventions., (© 2021 S. Karger AG, Basel.)

Background: The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited., Objective: Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization., Methods: Clinicians reported patients with psoriasis with confirmed/suspected COVID-19 via an international registry, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection. Multiple logistic regression was used to assess the association between clinical and/or demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviors., Results: Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% were receiving a nonbiologic, and 10% were not receiving any systemic treatment for psoriasis. In all, 348 patients (93%) were fully recovered from COVID-19, 77 (21%) were hospitalized, and 9 (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted odds ratio [OR] = 1.59 per 10 years; 95% CI = 1.19-2.13), male sex (OR = 2.51; 95% CI = 1.23-5.12), nonwhite ethnicity (OR = 3.15; 95% CI = 1.24-8.03), and comorbid chronic lung disease (OR = 3.87; 95% CI = 1.52-9.83). Hospitalization was more frequent in patients using nonbiologic systemic therapy than in those using biologics (OR = 2.84; 95% CI = 1.31-6.18). No significant differences were found between classes of biologics. Independent patient-reported data (n = 1626 across 48 countries) suggested lower levels of social isolation in individuals receiving nonbiologic systemic therapy than in those receiving biologics (OR = 0.68; 95% CI = 0.50-0.94)., Conclusion: In this international case series of patients with moderate-to-severe psoriasis, biologic use was associated with lower risk of COVID-19-related hospitalization than with use of nonbiologic systemic therapies; however, further investigation is warranted on account of potential selection bias and unmeasured confounding. Established risk factors (being older, being male, being of nonwhite ethnicity, and having comorbidities) were associated with higher hospitalization rates., (Copyright © 2020. Published by Elsevier Inc.)

Importance: Ustekinumab, a monoclonal antibody targeting interleukin 12/23p40 (IL-12/23p40), is effective in the treatment of moderate to severe psoriasis, psoriatic arthritis, and Crohn disease. In 2011, a meta-analysis of randomized clinical trials reported a potential risk of severe cardiovascular events (SCEs) within the first few months after the initiation of anti-IL-12/23p40 antibodies., Objective: To assess whether the initiation of ustekinumab treatment is associated with increased risk of SCEs., Design, Setting, and Participants: This case-time-control study used data from the French national health insurance database, covering 66 million individuals, on all patients exposed to ustekinumab between April 1, 2010, and December 31, 2016, classified according to their cardiovascular risk level (high- and low-risk strata). The risk period was the 6 months before the SCE, defined as acute coronary syndrome or stroke, and the reference period was the 6 months before the risk period. Statistical analysis was performed from September 20, 2017, to July 6, 2018., Exposure: The initiation of ustekinumab treatment was screened during the risk and reference periods., Main Outcomes and Measures: Odds ratios for the risk of SCE after the initiation of ustekinumab treatment were calculated., Results: Of the 9290 patients exposed to ustekinumab (4847 men [52%]; mean [SD] age, 43 [14] years), 179 experienced SCEs (65 cases of acute coronary syndrome, 68 cases of unstable angina, and 46 cases of stroke). Among patients with a high cardiovascular risk, a statisically significant association between initiaton of ustekinumab treatment and SCE occurrence was identified (odds ratio, 4.17; 95% CI, 1.19-14.59). Conversely, no statistically significant association was found among patients with a low cardiovascular risk (odds ratio, 0.30; 95% CI, 0.03-3.13)., Conclusions and Relevance: This study suggests that the initiation of ustekinumab treatment may trigger SCEs among patients at high cardiovascular risk. In line with the current mechanistic models for atherosclerotic disease, the period after the initiation of anti-IL-12/23p40 may be associated with atherosclerotic plaque destabilization via the inhibition of helper T cell subtype 17. Although the study interpretation is limited by its observational design, these results suggest that caution may be needed in the prescription of ustekinumab to patients at high cardiovascular risk.

Background: Palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH) are rare variants of psoriasis. Knowledge of the efficacy of biologics is scarce., Objectives: To evaluate the real-life efficacy of tumour necrosis factor blockers and ustekinumab in PPP and in ACH., Methods: A multicentre retrospective descriptive study was conducted in 19 dermatology departments, including all patients with PPP or ACH seen from 2014 to 2016 who received one of the studied biologics. The data were collected by a standardized document. Factors associated with complete clearance (CC) were analysed by multivariate analysis, estimating odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Among 92 patients included, 50 received adalimumab, 44 ustekinumab, 36 etanercept and 31 infliximab. Improvement and CC were observed in 83.9% and 20.0% patients receiving infliximab, 75.0% and 38.6% ustekinumab, 57.1% and 20.0% etanercept and 60.4% and 29.2% adalimumab. We found no significant difference in CC rates or duration of treatment among the biological treatments (P = 0.18 and P = 0.10, respectively). On multivariate analysis, CC with etanercept was associated with the ACH form and not smoking [OR = 9.5 (95% CI 1.1-82.7), P = 0.04 and 0.1 (0.01-0.9), P = 0.04]; with ustekinumab, male sex and absence of obesity [6.0 (1.3-28.6), P = 0.02 and 4.7 (1.0-22.7), P = 0.05]; with adalimumab, the ACH form [11.9 (2.7-52.3), P = 0.001]; and with infliximab, obesity [5.6 (1.1-29.4), P = 0.04]., Conclusions: We found no difference in efficacy between TNF blockers and ustekinumab and among the three different TNF blockers in real life for PPP or ACH, which reveals the heterogeneity of clinical response to biologics in pustular psoriasis as compared with plaque psoriasis., (© 2020 European Academy of Dermatology and Venereology.)

Background: Numerous inclusion and exclusion criteria are involved in phase III moderate to severe psoriasis trials investigating the safety and efficacy of biologics. This questions the generalization of results., Methods: In this cohort study, we applied inclusion/exclusion criteria for phase III trials from original protocols (adalimumab - REVEAL, ustekinumab - PHOENIX, brodalumab - AMAGINE, secukinumab FIXTURE) to all patients enrolled in the PsoBioTeq prospective registry who received a biological agent for the first time between July 2012 and November 2017. We then compared the efficacy, drug survival and occurrence of adverse events between patients who satisfied/did not satisfy the eligibility criteria for these phase III trials., Results: A total of 1267 patients were enrolled, of whom 993 (78.4%) were not eligible for at least one RCT (randomized controlled trial) and 251 (19.1%) did not meet the PASI/PGA severity requirements. Apart from disease severity, the most frequent criteria resulting in exclusion were as follows: non-plaque psoriasis (12.6%), significant cardiac disease (8.4%), significant liver disease (7.3%), elevated liver enzymes (4.9-9.6%) and personal history of diabetes (9.2%). There was no difference in drug survival between the two groups. The incidence ratio of adverse events was significantly lower in eligible versus non-eligible patients [0.78 (95% CI 0.62-0.97) (P = 0.03)]., Conclusion: The majority of patients treated with biologics in the PsoBioTeq real-life registry would not have been eligible for phase III moderate to severe psoriasis trials. Patients not eligible for psoriasis phase III clinical trials have a higher incidence of adverse events., (© 2019 European Academy of Dermatology and Venereology.)

Background: Randomized controlled trials have shown the efficacy and safety of brodalumab in patients with moderate to severe plaque psoriasis., Objective: To evaluate the efficacy and safety of brodalumab through 120 weeks of treatment in the AMAGINE-2 trial., Methods: Patients received ustekinumab through week 52 followed by brodalumab 210 mg every 2 weeks, continuous brodalumab 210 mg every 2 weeks, or any dose of brodalumab. Efficacy data were reported through 120 weeks by using observed data, last observation carried forward, and nonresponder imputation analyses., Results: Of patients who received brodalumab 210 mg every 2 weeks, 84.4%, 75.6%, and 61.1% achieved 75%, 90%, and 100% improvement from baseline in Psoriasis Area and Severity Index at 120 weeks (observed data analysis), respectively. Patients who received brodalumab 210 mg every 2 weeks after receiving ustekinumab through 52 weeks achieved a similar skin clearance response as patients who received continuous brodalumab 210 mg every 2 weeks. Safety through 120 weeks was comparable to that of the blinded study periods., Limitations: A large number of discontinuations toward the end of the study (31% in the final 6 months) were due to early termination and led to differences between observed data and nonresponder imputation results., Conclusions: Brodalumab is well tolerated and showed robust efficacy for more than 2 years., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Pustular psoriasis is a clinically heterogeneous entity of different, orphan disease subtypes, among which the most clearly defined are generalized pustular psoriasis, palmoplantar psoriasis, and acrodermatitis continua of Hallopeau. Although phenotypically and genetically distinct from psoriasis vulgaris, these subtypes may be associated with plaque psoriasis lesions, establishing the rationale for their inclusion in the psoriasis spectrum. Unlike psoriasis, however, their genetic background is thought to be mainly monogenic, as shown by the recent identification of mutations in 3 different genes of the skin innate immune system; IL36RN, CARD14 and AP1S3. These major advances in the understanding of the disease pathogenesis have led to the design and ongoing development of tailored therapeutic approaches, which are highly necessary given the refractory nature of pustular psoriasis in response to most available antipsoriatic drugs.

Background: Palmoplantar pustular psoriasis (PPP) is a debilitating disease of the palms and/or soles that is resistant to treatment. Secukinumab, an anti-interleukin 17A monoclonal antibody, is highly efficacious in the treatment of moderate-to-severe psoriasis., Objective: The primary objective was to determine the rate of achievement of a 75% improvement from baseline in Palmoplantar Psoriasis Area and Severity Index (PPPASI75) with secukinumab at week 16 versus with placebo (at a 2.5% significance level)., Methods: 2PRECISE was a phase 3b multicenter, randomized, double-blind, placebo-controlled, parallel-group study comparing treatment with 300 mg of secukinumab (n = 79), 150 mg of secukinumab (n = 80), and placebo (n = 78) in subjects with moderate-to-severe PPP over a period of 52 weeks., Results: The primary end point was not met. At week 16, 26.6% of subjects treated with 300 mg of secukinumab achieved PPPASI75 versus 14.1% of those who received placebo (P = .0411) (odds ratio, 2.62; 95% confidence interval, 1.04-6.60). At week 52, 41.8% of subjects treated with 300 mg of secukinumab had achieved ppPASI75. More Dermatology Life Quality Index responses of 0 or 1 were achieved with 300 mg of secukinumab (13.0%) than with placebo (4.3%) at week 16. At week 52, 43.1% of subjects receiving 300 mg of secukinumab had a Dermatology Life Quality Index response of 0 or 1. No unexpected adverse events were observed., Limitations: Small sample size and characteristics of the PPP disease course., Conclusion: Patients with PPP who were treated with secukinumab, 300 mg, showed benefit in terms of PPPASI75 responses over 52 weeks and improved quality of life., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Although existing psoriasis treatments are effective and well tolerated in many patients, there is still a need for new effective targeted treatment options. Tofacitinib is an oral Janus kinase inhibitor that has been investigated in patients with moderate-to-severe chronic plaque psoriasis., Objectives: To consider the benefits and risks of tofacitinib in patients with moderate-to-severe psoriasis., Methods: Data were pooled from one phase II, four phase III and one long-term extension study comprising 5204 patient-years of tofacitinib treatment. Efficacy end points included patients achieving Physician's Global Assessments of 'clear' or 'almost clear', ≥ 75% and ≥ 90% reduction in Psoriasis Area and Severity Index (coprimary end points) and improvements in Dermatology Life Quality Index score, Hospital Anxiety and Depression Scale depression score and Itch Severity Item score, at weeks 16 and 52. Safety data were summarized for 3 years of tofacitinib exposure., Results: Tofacitinib 5 and 10 mg twice daily (BID) showed superiority over placebo for all efficacy end points at week 16, with response maintained for 52 weeks of continued treatment. Tofacitinib improved patients' quality of life and was well tolerated. Rates of safety events of interest (except herpes zoster) were similar to those in the published literature and healthcare databases for other systemic psoriasis therapies. Tofacitinib 10 mg BID demonstrated greater efficacy than 5 mg BID., Conclusions: Tofacitinib has a benefit-risk profile in moderate-to-severe psoriasis consistent with that of other systemic treatments., (© 2018 British Association of Dermatologists.)

Background: In the late 2000s, the introduction of biologics transformed the prognosis for patients with moderate-to-severe psoriasis. We hypothesized that treatment with biologics may associate with a reduction in the hospitalization rate for psoriasis flares., Objective: To analyse changes over time in the hospitalization rate for psoriasis flares., Methods: We included inpatient stays in any of nine French hospitals between 2005 and 2015 for a psoriasis flare, as documented in the national inpatient database. In two centres, we also analysed data from the individual patients' electronic medical records., Results: A total of 3572 stays were included. The introduction of biologics was not associated with a decrease in the number of hospitalizations for a psoriasis flare; on the contrary, we observed a non-significant increase in the number of hospitalizations (13 hospitalizations for psoriasis flares per quarter per 10 000 beds). In the two-centre study, the introduction of biologics was associated with a significant increase in the hospitalization of patients receiving topical treatments only (520 hospitalizations per year per 10 000 beds) and those with a first psoriasis flare., Conclusion: The number of hospitalizations for a psoriasis flare tended to increase between 2005 and 2015. The availability of additional treatment options might have increased patient demand and/or broadened the indications in clinical practice., (© 2018 European Academy of Dermatology and Venereology.)

Background: Risankizumab is a humanised IgG1 monoclonal antibody that binds to the p19 subunit of interleukin-23, inhibiting this key cytokine and its role in psoriatic inflammation. We aimed to assess the efficacy and safety of risankizumab compared with placebo or ustekinumab in patients with moderate-to-severe chronic plaque psoriasis., Methods: UltIMMa-1 and UltIMMa-2 were replicate phase 3, randomised, double-blind, placebo-controlled and active comparator-controlled trials done at 139 sites in Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Japan, Mexico, Poland, Portugal, South Korea, Spain, and the USA. Eligible patients were 18 years or older, with moderate-to-severe chronic plaque psoriasis. In each study, patients were stratified by weight and previous exposure to tumour necrosis factor inhibitor and randomly assigned (3:1:1) by use of interactive response technology to receive 150 mg risankizumab, 45 mg or 90 mg ustekinumab (weight-based per label), or placebo. Following the 16-week double-blind treatment period (part A), patients initially assigned to placebo switched to 150 mg risankizumab at week 16; other patients continued their originally randomised treatment (part B, double-blind, weeks 16-52). Study drug was administered subcutaneously at weeks 0 and 4 during part A and at weeks 16, 28, and 40 during part B. Co-primary endpoints were proportions of patients achieving a 90% improvement in the Psoriasis Area Severity Index (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16 (non-responder imputation). All efficacy analyses were done in the intention-to-treat population. These trials are registered with ClinicalTrials.gov, numbers NCT02684370 (UltIMMa-1) and NCT02684357 (UltIMMa-2), and have been completed., Findings: Between Feb 24, 2016, and Aug 31, 2016, 506 patients in UltIMMa-1 were randomly assigned to receive 150 mg risankizumab (n=304), 45 mg or 90 mg ustekinumab (n=100), or placebo (n=102). Between March 1, 2016, and Aug 30, 2016, 491 patients in UltIMMa-2 were randomly assigned to receive 150 mg risankizumab (n=294), 45 mg or 90 mg ustekinumab (n=99), or placebo (n=98). Co-primary endpoints were met for both studies. At week 16 of UltIMMa-1, PASI 90 was achieved by 229 (75·3%) patients receiving risankizumab versus five (4·9%) receiving placebo (placebo-adjusted difference 70·3% [95% CI 64·0-76·7]) and 42 (42·0%) receiving ustekinumab (ustekinumab-adjusted difference 33·5% [22·7-44·3]; p<0·0001 vs placebo and ustekinumab). At week 16 of UltIMMa-2, PASI 90 was achieved by 220 (74·8%) patients receiving risankizumab versus two (2·0%) receiving placebo (placebo-adjusted difference 72·5% [95% CI 66·8-78·2]) and 47 (47·5%) receiving ustekinumab (ustekinumab-adjusted difference 27·6% [16·7-38·5]; p<0·0001 vs placebo and ustekinumab). In UltIMMa-1, sPGA 0 or 1 at week 16 was achieved by 267 (87·8%) patients receiving risankizumab versus eight (7·8%) receiving placebo (placebo-adjusted difference 79·9% [95% CI 73·5-86·3]) and 63 (63·0%) receiving ustekinumab (ustekinumab-adjusted difference 25·1% [15·2-35·0]; p<0·0001 vs placebo and ustekinumab). In UltIMMa-2, 246 (83·7%) patients receiving risankizumab versus five (5·1%) receiving placebo (placebo-adjusted difference 78·5% [95% CI 72·4-84·5]) and 61 (61·6%) receiving ustekinumab achieved sPGA 0 or 1 at week 16 (ustekinumab-adjusted difference 22·3% [12·0-32·5]; p<0·0001 vs placebo and ustekinumab). The frequency of treatment-emergent adverse events in UltIMMa-1 and UltIMMa-2 was similar across risankizumab (part A: 151 [49·7%] of 304 and 134 [45·6%] of 294; part B: 182 [61·3%] of 297 and 162 [55·7%] of 291), placebo (part A: 52 [51·0%] of 102 and 45 [45·9%] of 98), ustekinumab (part A: 50 [50·0%] of 100 and 53 [53·5%] of 99; part B: 66 [66·7%] of 99 and 70 [74·5%] of 94), and placebo to risankizumab (part B: 65 [67·0%] of 97 and 61 [64·9%] of 94) treatment groups throughout the study duration., Interpretation: Risankizumab showed superior efficacy to both placebo and ustekinumab in the treatment of moderate-to-severe plaque psoriasis. Treatment-emergent adverse event profiles were similar across treatment groups and there were no unexpected safety findings., Funding: AbbVie and Boehringer Ingelheim., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Patients with pustular psoriasis or related pustular diseases may have genetic abnormalities impairing the function of key players of the innate skin immune system. Recently, identification of these abnormalities has changed the paradigm of several of these diseases. These include generalized pustular psoriasis, palmoplantar pustular psoriasis and acrodermatitis continua of Hallopeau, and also drug-induced acute exanthematous generalized pustular eruption. Identified mutations in IL36RN, CARD14 and AP1S3 in different groups of patients lead to enhanced inflammatory cascade in several cellular subtypes including keratinocytes, and to the recruitment and activation of neutrophils and macrophages. These insights have unveiled pathophysiological features that shift the existing paradigms and emphasize the autoinflammatory nature of skin pustular disorders. They also highlight the crucial role of the innate immune system across entities belonging to the psoriasis disease spectrum, allowing identification of new appealing therapeutic targets., (© 2018 British Association of Dermatologists.)

Background: ABP 501, a U.S.A. Food and Drug Administration- and European Medicines Agency-approved biosimilar, is highly similar to adalimumab in structure, function and pharmacokinetics., Objectives: To demonstrate similarity in efficacy, safety and immunogenicity of ABP 501 vs. adalimumab for moderate-to-severe plaque psoriasis (clinical trial: NCT01970488)., Methods: Patients were randomized (1 : 1) to receive ABP 501 or adalimumab 40 mg every 2 weeks for 16 weeks. At week 16, patients with ≥ 50% improvement from baseline in Psoriasis Area and Severity Index (PASI) score were eligible to continue to week 52. Patients receiving ABP 501 continued; adalimumab patients were rerandomized (1 : 1) to continue adalimumab or undergo a single transition to ABP 501. Key efficacy assessments included percentage PASI improvement from baseline, PASI responders and mean change in affected body surface area from baseline to weeks 16, 32 and 50. Safety was monitored via adverse events (AEs) and antidrug antibodies (ADAs) were assessed., Results: A total of 308 patients were rerandomized at week 16 (ABP 501/ABP 501, n = 152; adalimumab/adalimumab, n = 79; adalimumab/ABP 501, n = 77). PASI percentage improvements from baseline were similar across groups for weeks 16, 32 and 50 (range: 85·8-88·2%), with no significant differences detected across groups in percentages of PASI 50, 75, 90 and 100 responders. Changes from baseline in percentage body surface area affected were similar across groups and time points. No new safety signals were detected. AEs were balanced between groups. Percentages of patients with binding and neutralizing ADAs were similar across treatments., Conclusions: ABP 501 and adalimumab have similar clinical efficacy, safety and immunogenicity profiles over 52 weeks, including after single transition, in this patient population., (© 2017 British Association of Dermatologists.)

Background: Infections are associated with biological therapies in psoriasis., Objectives: To summarize the incidence of infections in patients with moderate-to-severe psoriasis treated with ixekizumab, an anti-interleukin-17A monoclonal antibody., Methods: Infections are summarized from an integrated database of seven controlled and uncontrolled ixekizumab psoriasis trials. Data are presented from placebo-controlled induction (weeks 0-12; UNCOVER-1, UNCOVER-2 and UNCOVER-3) and maintenance periods (weeks 12-60; UNCOVER-1 and UNCOVER-2), and all patients exposed to ixekizumab pooled from all seven trials. Comparisons with etanercept were made during the induction period of two trials (UNCOVER-2 and UNCOVER-3). Incidence and exposure-adjusted incidence rates (IRs) per 100 patient-years (PYs) are reported., Results: Overall, 4209 patients were treated with ixekizumab (6480 PY). During induction (weeks 0-12), overall infection rates were higher in patients treated with ixekizumab (27%) vs. placebo (23%, P < 0·05); however, specific infection rates were comparable overall across treatment groups. IRs of infections did not increase with longer-term exposure. For all patients treated with ixekizumab (all seven trials), the incidence of serious infections was low (2%, IR 1·3). Candida infections, including eight cases of oesophageal candidiasis, were adequately managed with antifungal therapy, were noninvasive and did not lead to discontinuation., Conclusions: Overall, infections occurred in a higher percentage of patients treated with ixekizumab vs. placebo during the first 12 weeks of treatment; however, specific infection rates were comparable overall across treatment groups. Incidences of serious infections were low and similar across treatment groups., (© 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Decision-making is a complex process. The aim of our study was to assess factors associated with the choice of the first biological treatment in patients with moderate-to-severe psoriasis., Methods: Data on all patients included in the French prospective, observational, cohort, Psobioteq and initiating a first biologic prescription between July 2012 and July 2016 were analysed. Demographic information and clinical features were collected during routine clinical assessments by the dermatology team at the recruiting centres using a standardized case report form. The primary outcome was the nature of the first biologic treatment. Four groups were identified as follows: adalimumab, etanercept, ustekinumab and infliximab groups. Factors associated with the choice of the first biological agent were determined by a multinomial logistic regression model adjusted on year of inclusion., Results: The study population included the 830 biological-naïve patients who initiated a first biological agent. The mean age was 46.6 years (±SD 13.9), and 318 patients (38.3%) were female. The most commonly prescribed biologic was adalimumab: 355 (42.8%) patients, then etanercept (n = 247, 29.8%), ustekinumab (n = 194, 23.4%) and infliximab (n = 34, 4.0%). In the multinomial logistic regression analysis, patients were significantly more likely to receive adalimumab if they had a severe psoriasis as defined by baseline PASI or if they had psoriatic arthritis compared to etanercept (aOR, 0.42; 95% CI, 0.16-1.07) and ustekinumab (aOR, 0.15; 95% CI, 0.04-0.52). Patients were significantly more likely to receive ustekinumab (aOR, 2.39; 95% CI, 1.04-5.50) if they had a positive screening for latent tuberculosis compared to adalimumab. Younger patients were also more likely to receive ustekinumab. Patients with chronic obstructive pulmonary disease were more likely to be prescribed ustekinumab or etanercept compared to adalimumab. There was a trend in favour of etanercept prescription in patients with cardiovascular comorbidities, metabolic syndrome and in patients with a history of cancer., Conclusion: We identified patient- and disease-related factors that have important influence on the choice of the first biological agent in clinical practice. Clinicians appear to have a holistic approach to patient characteristics when choosing a biological agent in psoriasis., (© 2017 European Academy of Dermatology and Venereology.)

Psoriasis is a chronic, immune-mediated disease affecting more than 100 million people worldwide and up to 2.2% of the UK population. The aetiology of psoriasis is thought to originate from an interplay of genetic, environmental, infectious and lifestyle factors. The manner in which genetic and environmental factors interact to contribute to the molecular disease mechanisms has remained elusive. However, the interleukin 23 (IL-23)/T-helper 17 (T H 17) immune axis has been identified as a major immune pathway in psoriasis disease pathogenesis. Central to this pathway is the cytokine IL-23, a heterodimer composed of a p40 subunit also found in IL-12 and a p19 subunit exclusive to IL-23. IL-23 is important for maintaining T H 17 responses, and levels of IL-23 are elevated in psoriatic skin compared with non-lesional skin. A number of agents that specifically inhibit IL-23p19 are currently in development for the treatment of moderate-to-severe plaque psoriasis, with recent clinical trials demonstrating efficacy with a good safety and tolerability profile. These data support the role of this cytokine in the pathogenesis of psoriasis. A better understanding of the IL-23/T H 17 immune axis is vital and will promote the development of additional targets for psoriasis and other inflammatory diseases that share similar genetic aetiology and pathogenetic pathways., (© 2017 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey data were not analysed to account for cultural and healthcare system differences across European countries (EC)., Objective: To utilize MAPP data to characterize psoriasis in Spanish patients, including severity assessment and Dermatology Life Quality Index (DLQI)., Methods: The MAPP survey was conducted between June and August 2012. This analysis included 1700 patients with self-reported psoriasis (without psoriatic arthritis) from France (n = 349), Germany (n = 311), Italy (n = 359), Spain (n = 354) and the United Kingdom (n = 327)., Results: Patients from Spain vs. other EC self-reported higher mean body mass index (26.9 vs. 25.6, P ≤ 0.001), lower prevalence of depression (6% vs. 12%, P = 0.002) and higher mean self-perceived psoriasis severity at its worst (5.92 vs. 5.33, P < 0.001) despite lower estimated body-surface-area involvement. Overall, patients from Spain vs. other EC had lower mean global DLQI scores (4.70 vs. 6.06, P = 0.001) and lower mean scores for each DLQI dimension [all P < 0.001, except leisure (P = 0.002), treatment (P = 0.002), and work and school (P = 0.005)]. Higher DLQI values were inversely associated with age and directly correlated with perceived severity. Palmoplantar, nail and scalp psoriasis were reported less frequently in Spanish patients (P = 0.026) and were associated with higher DLQI values (P < 0.01). Spanish patients were more likely to have seen multiple healthcare providers (HCPs; P < 0.001) and achieve therapeutic goals (P < 0.001), but current treatments were similar to patients in other EC., Conclusions: In the MAPP survey, Spanish patients differed from other EC in several characteristics, including comorbidities, extent and distribution of psoriasis lesions, perception of severity and impact on quality of life. Their perception of psoriasis severity was higher despite a lower estimated extent, and DLQI scores were significantly lower. Spanish patients had more HCP visits and a higher rate of therapeutic goal achievement. These differences might be attributed to cultural factors, phenotypical variation and differences in HCP access., (© 2017 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Around two-thirds of patients with psoriasis do not adhere to topical treatment. The Topical Treatment Optimization Programme (TTOP), a five-element tool, includes guidance for the conversation between dermatologists/nurses and patients, patient information material, telephone/e-mail helpdesks and treatment reminders. It has been developed by patients and dermatologists to help increase adherence to treatment in psoriasis., Objectives: To compare TTOP with standard of care ('non-TTOP') within a large European investigator-initiated study, PSO-TOP (clinicaltrials.gov NCT01587755)., Methods: Patients with mild-to-moderate psoriasis received calcipotriol/betamethasone dipropionate gel as standardized study medication and were randomized 1 : 1 to either TTOP or non-TTOP management. Study medication was applied once daily for 8 weeks followed by 'as needed' application for an additional 56 weeks. Response was defined as a Physician's Global Assessment (PGA) of 'clear' or 'almost clear'., Results: In 1790 patients (full analysis set), response rates after 8 weeks (primary objective) were significantly higher for TTOP (36·3%) than for non-TTOP (31·3%, P = 0·0267). Better clinical outcome was accompanied by higher rates of patients feeling well informed about their skin condition, treatment and other factors related to adherence, but the Dermatology Life Quality Index was not statistically different. TTOP patients regarded the structured one-to-one conversations with their dermatologist/nurse as the most important element of TTOP., Conclusions: Patients randomized to the TTOP intervention had a better clinical response than patients receiving standard of care. Improved communication between the healthcare provider and patient might be an important element in increasing adherence to topical therapy in psoriasis., (© 2017 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Immunosuppressed patients are at risk of severe viral infections-related complications. National and international vaccination guidelines have been developed to decrease the mortality risk associated with these infections. However, a summary of these guidelines and the value of immunisation in this population is missing., Objectives: To summarize specific guidelines regarding vaccination in immunosuppressed patients., Methods: We performed a literature search based on last update vaccine guidelines in immunosuppressed adult patients published between 1/1/2005-1/31/2016 in English or French language using PubMed, Cochrane and Embase, as well as relevant medical society websites., Results: Of the 389 citations identified, 12 guidelines were selected Three additional guidelines were selected by searching on the websites from medical societies of each specialty. 15 guidelines were included, involving 19 medical societies issued from the US (n = 6), international collaboration (n = 3), UK (n = 2), Canada (n = 1), Australia (n = 1), France (n = 1), and Germany (n = 1). These guidelines provide recommendations on vaccination in asplenic patients (n = 5), cancer patients (n = 4), HIV patients (n = 5), hematopoietic stem cell recipients (n = 4), inflammatory bowel diseases patients (n = 5), psoriasis patients (n = 4), primary immunocompromised patients (n = 3), inflammatory rheumatic diseases patients (n = 6), and solid organ transplant recipients (n = 5). All guidelines recommended pneumococcal and injectable influenza vaccines. Other inactivated vaccines were recommended only in high risk patients. Live vaccines were usually contraindicated in patients under immunosuppressive therapy and/or in HIV patients with a CD4 count under 200/mm 3 ., Conclusion: Pneumococcal and injectable influenza are the two essential vaccines recommended in all immunocompromised patients. Other inactivated vaccines are only indicated in high risk patients. Live vaccines are usually contraindicated., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: ABP 501 is a biosimilar of adalimumab., Objective: We sought to compare the efficacy and safety of ABP 501 with adalimumab., Methods: This 52-week, double-blind study randomized patients with moderate to severe psoriasis to ABP 501 or adalimumab. At week 16, those with 50% or more improvement in Psoriasis Area and Severity Index score from baseline on ABP 501 continued the same treatment, whereas adalimumab-treated patients were rerandomized to adalimumab or ABP 501. Clinical similarity in Psoriasis Area and Severity Index percent improvement from baseline to week 16 (primary end point) was established if the point estimate of treatment difference and its 2-sided 95% confidence interval between groups was within equivalence margin of ±15. Patients, including those undergoing a single transition at week 16, were evaluated for safety and immunogenicity., Results: Psoriasis Area and Severity Index percent improvement at week 16 was 80.9 for ABP 501 and 83.1 for adalimumab (least-square mean difference -2.18 [95% confidence interval -7.39 to 3.02]). Adverse events (67.2% [117/174] vs 63.6% [110/173]) and antidrug antibody incidence (55.2% [96/174] vs 63.6% [110/173]) for ABP 501 vs adalimumab were similar. Safety, including immunogenicity, was similar among groups after single transition (week 20)., Limitations: The 52-week data are not reported here., Conclusions: ABP 501 was shown to be clinically similar to adalimumab. Safety and immunogenicity were not impacted immediately after single transition (adalimumab to ABP 501)., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)