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Background: Biologics are the cornerstone of treatment of patients with moderate‐to‐severe plaque psoriasis and switches between biologics are frequently needed to maintain clinical improvement over time. Objectives: The main purpose of this study was to describe precisely switches between biologics and how their pattern changed over time with the recent availability of new biologic agents. Methods: We included patients receiving a first biologic agent in the Psobioteq multicenter cohort of adults with moderate‐to‐severe psoriasis receiving systemic treatment. We described switches between biologics with chronograms, Sankey and Sunburst diagrams, assessed cumulative incidence of first switch by competing risks survival analysis and reasons for switching. We assessed the factors associated with the type of switch (intra‐class – i.e. within the same therapeutic class ‐ vs. inter‐class) in patients switching from a TNF‐alpha inhibitor using multivariate logistic regression. Results: A total of 2153 patients was included. The cumulative incidence of switches from first biologic was 34% at 3 years. Adalimumab and ustekinumab were the most prescribed biologic agents as first and second lines of treatment. The main reason for switching was loss of efficacy (72%), followed by adverse events (11%). Patients receiving a TNF‐alpha inhibitor before 2016 mostly switched to ustekinumab, whereas those switching in 2016 or after mostly switched to an IL‐17 inhibitor. Patients switching from a first‐line TNF‐alpha inhibitor before 2016 were more likely to switch to another TNF‐alpha inhibitor compared with patients switching since 2018. Patients switching from etanercept were more likely to receive another TNF‐alpha inhibitor rather than another therapeutic class of bDMARD compared with patients switching from adalimumab. Conclusion: This study described the switching patterns of biologic treatments and showed how they changed over time, due to the availability of the new biologic agents primarily IL‐17 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Acral pustular disease within the pustular psoriasis/psoriasis‐like spectrum mainly includes palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH). Scarce data argue for a distinction between these two entities, but no study has compared the clinical and epidemiologic characteristics of ACH and PPP. Objectives: We aimed to perform a comparative description of the epidemiological and clinical characteristics of PPP and ACH in a multicentre retrospective cohort. Methods: In this multicentre national retrospective cohort study, we compared the epidemiological characteristics, comorbidities and psoriasis characteristics of patients with PPP and ACH. Results: A total of 234 patients were included: 203 (87%) with PPP, 18 (8%) with ACH and 13 (6%) with both, according to 2017 ERASPEN criteria. As compared with ACH, PPP was associated with female sex, smoking activity and higher median BMI (P = 0.01, P = 0.02 and P = 0.05 respectively). A family background of psoriasis was more frequent in PPP than ACH. Age of onset of palmoplantar disease was similar between PPP and ACH patients, median age 44 and 48 years respectively. Peripheral joint inflammatory involvement was the only rheumatic disease associated with ACH. The association with another psoriasis type was similar in PPP and ACH (57.6% and 61.1% respectively). Conclusion: Our study confirms in a large PPP cohort the predominance of females and a high prevalence of smoking and elevated body mass index but also shows an association of these features in PPP as compared with ACH. In addition, it highlights peripheral arthritis as the only arthritis endotype associated with ACH. Increased knowledge of the immunogenetic backgrounds underlying these two entities is warranted to better stratify pustular psoriasis or psoriasis‐like entities for precision medicine. [ABSTRACT FROM AUTHOR]

Summary: Background: Risankizumab has demonstrated efficacy and safety in patients with moderate‐to‐severe plaque psoriasis in randomized clinical trials. Objectives: To evaluate safety data from risankizumab psoriasis phase I–III clinical trials. Methods: Short‐term safety (through week 16) was analysed using integrated data from five phase II and III clinical trials. Long‐term safety was evaluated using integrated data from 17 phase I–III completed and ongoing trials. Results: Short‐term safety analyses included 1306 patients receiving risankizumab 150 mg and 300 patients receiving placebo [402·2 and 92·0 patient‐years (PY) of exposure, respectively]. Long‐term analyses included 3072 risankizumab‐treated patients (exposure: 7927 PY). The median (excluding four outliers) treatment duration was 2·9 years (range 2 days to 5·9 years). Exposure‐adjusted adverse event rates did not increase with long‐term treatment (318 vs. 171 events per 100 PY for short‐ and long‐term analyses). With long‐term risankizumab treatment, rates of serious adverse events were 7·8 per 100 PY, serious infections 1·2 per 100 PY, nonmelanoma skin cancer (NMSC) 0·7 per 100 PY, malignant tumours excluding NMSC 0·5 per 100 PY, and adjudicated major adverse cardiovascular events 0·3 per 100 PY, with no important identified risks. Limitations include that the study inclusion and exclusion criteria varied and that three studies enrolled ≤ 50 patients. Conclusions: Risankizumab demonstrated a favourable safety profile over short‐ and long‐term treatment in patients with moderate‐to‐severe psoriasis. Whatis already known about this topic? In clinical trials of patients with moderate‐to‐severe plaque psoriasis, risankizumab, a selective interleukin‐23 inhibitor, was well tolerated and efficacious. Whatdoes this study add? In this comprehensive evaluation of risankizumab safety in patients with moderate‐to‐severe psoriasis, adverse event rates were comparable between risankizumab (n = 1306, 402 patient‐years) and placebo (n = 300, 92 patient‐years) in the short‐term (16‐week) analysis set, and were consistent with those in the long‐term analysis (n = 3072, 7927 patient‐years of risankizumab exposure).These findings are consistent with the known safety profile of risankizumab and support its long‐term use in moderate‐to‐severe psoriasis. Linked Comment: S. Mirali et al. Br J Dermatol 2022; 186:394–395. Plain language summary available online [ABSTRACT FROM AUTHOR]

Prof. Warren reports grants and personal fees from Abbvie, grants and personal fees from Celgene, grants and personal fees from Eli Lilly, grants and personal fees from Novartis, personal fees from Sanofi, grants and personal fees from UCB|, grants and personal fees from Almirall, grants and personal fees from Amgen, grants and personal fees from Janssen, grants and personal fees from Leo, grants and personal fees from Pfizer, personal fees from Arena, personal fees from Avillion, personal fees from Bristol Myers Squibb, personal fees from Boehringer Ingelheim, outside the submitted work. We are grateful to all the patients who have contributed to PsoProtect I Me i , the professional and patient organisations who supported or promoted PsoProtect I M i e and for the input of Prof Lars Iversen, Prof Nick Reynolds, Prof Joel Gelfand, Ms Christine Janus and Ms Melissa Sweeney through their vital contributions. Dr. Di Meglio reports grants and personal fees from UCB, personal fees from Novartis, personal fees from Janssen, outside the submitted work. [Extracted from the article]

Summary: 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. What is already known about this topic? At the beginning of the coronavirus disease 2019 (COVID‐19) pandemic, patients with immune‐mediated inflammatory diseases (IMIDs) on targeted systemic therapies were considered to be at higher risk of severe COVID‐19.Subsequent clinician‐reported registry data suggest that targeted systemic therapy use is associated with fewer adverse COVID‐19 outcomes compared with no systemic therapy. What does this study add? We characterize shielding behaviour in 3720 patients with IMIDs from a global self‐report survey.Use of targeted systemic therapy associates with increased shielding behaviour, compared with standard systemics or no therapy, as do demographic risk factors for severe COVID‐19 including male sex and obesity.Greater risk‐mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID‐19 outcomes.Behaviour variation across treatment groups reinforces the need for clear, evidence‐based patient communication on risk‐mitigation strategies.These data may help to inform updated public health guidelines as the pandemic continues. Linked Comment: G. Becher and A.D. Burden. Br J Dermatol 2021; 185:7–8. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A commonly used assessment is the Psoriasis Area and Severity Index (PASI), with an absolute value of 10 or more indicating severe disease.1 How patients perceive the severity of psoriasis and physicians' evaluations may be discordant, especially when lesions involve visible areas or are associated with itching. [Extracted from the article]

Summary: 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. What's already known about this topic? Psoriasis is a chronic, systemic inflammatory disease, which has a significant impact on patients' health‐related quality of life.Although several existing psoriasis treatments are efficacious and well tolerated in many patients, some patients require treatment switching, and a proportion of patients remain untreated or undertreated.Potential challenges to the use of existing therapies include safety issues and limited efficacy in some patients with conventional oral psoriasis treatments, inconvenience of topical treatments and the requirement for parenteral administration of biologics. What does this study add? Consistent efficacy and a safety profile consistent with that seen in rheumatoid arthritis, psoriatic arthritis and ulcerative colitis were demonstrated for oral tofacitinib in patients with moderate‐to‐severe psoriasis.Tofacitinib has a benefit–risk profile in patients with moderate‐to‐severe psoriasis that is consistent with that of other systemic psoriasis treatments. Linked Comment: Fleming. Br J Dermatol 2019; 180:13–14. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Between February 2011 and November 2018, we enrolled 25 patients including 13 women with PV (21) and GPP (4) at baseline, with a median age of 38 years, consulting for 31 flares with RTI symptoms. Overall, 21 of 25 patients had at least one positive multiplex PCR viral test, with I Rhinovirus i and I Coronavirus i as the most frequently detected pathogens, while only two of 25 bacterial swabs were positive (one each for I Staphylococcus aureus i and I Streptococcus dysgalactiae i ). All patients reported history of previous acute psoriasis flares following RTI, including two patients with GPP/DITRA sharing the homozygous c.80T>C; p.Leu27Pro severe mutation.[6] No genetic abnormality was detected in I IL36RN i , I CARD14 i and I AP1S3 i in other patients. [Extracted from the article]

Background Limited information is available regarding factors associated with long-term drug survival of infliximab for psoriasis in real life. Objectives The main aim pf this study was to identify predictors of long-term (>12 months) drug survival among patients treated with infliximab for psoriasis in a real-world clinical setting. Methods Retrospectively collected data, relating to disease, patient characteristics and treatment procedures, in a multicentre observational cohort of patients with moderate-to-severe plaque psoriasis treated with infliximab at eight university hospitals, 120 of whom maintained a response to infliximab for more than 12 months, were compared with prospectively collected data in the same centres from 54 patients who experienced secondary loss of response within a 12-month period. Results Mean duration of drug survival of infliximab in patients with long-term drug survival was 41.12 months ± 20.64 SD vs. 8.5 months ± 2.43 SD in patients with a secondary loss of response. Multivariate analysis identified greater disease severity at treatment onset ( PASI score >12) ( OR = 5.18, 95% CI: 1.60-16.77, P = 0.006), high levels of initial psoriasis clearance ( PASI-90 reduction or equivalent) ( OR = 18.50, 95% CI: 4.56-74.45, P = 0.0001) and combination with methotrexate ( OR = 13.15, 95% CI: 1.46-118.79, P = 0.022) as independent predictors of long-term drug survival and sustained efficacy of infliximab. Conclusion Positive predictors for long-term drug survival of infliximab in real life were identified. Their impact on treatment management should be addressed in further prospective trials. [ABSTRACT FROM AUTHOR]

The article discusses research that assessed the efficacy of anti-tumor necrosis factor (TNF)-alpha drugs in patients with hidradenitis suppurativa (HS). Topics covered include the initial characteristics of HS patients treated with an anti-TNF-alpha drug, factors associated with a complete or partial response to first-line anti-TNF-alpha therapy, and the modest and inconsistent efficacy of the therapy for moderate-to-severe HS.

Background: Early clinical studies suggested that the anti-interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis.Methods: In two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients receiving ustekinumab continued to receive ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of brodalumab every 2 weeks. The primary aims were to evaluate the superiority of brodalumab over placebo at week 12 with respect to at least a 75% reduction in the psoriasis area-and-severity index score (PASI 75) and a static physician's global assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well as the superiority of brodalumab over ustekinumab at week 12 with respect to a 100% reduction in PASI score (PASI 100).Results: At week 12, the PASI 75 response rates were higher with brodalumab at the 210-mg and 140-mg doses than with placebo (86% and 67%, respectively, vs. 8% [AMAGINE-2] and 85% and 69%, respectively, vs. 6% [AMAGINE-3]; P<0.001); the rates of sPGA scores of 0 or 1 were also higher with brodalumab (P<0.001). The week 12 PASI 100 response rates were significantly higher with 210 mg of brodalumab than with ustekinumab (44% vs. 22% [AMAGINE-2] and 37% vs. 19% [AMAGINE-3], P<0.001). The PASI 100 response rates with 140 mg of brodalumab were 26% in AMAGINE-2 (P=0.08 for the comparison with ustekinumab) and 27% in AMAGINE-3 (P=0.007). Rates of neutropenia were higher with brodalumab and with ustekinumab than with placebo. Mild or moderate candida infections were more frequent with brodalumab than with ustekinumab or placebo. Through week 52, the rates of serious infectious episodes were 1.0 (AMAGINE-2) and 1.3 (AMAGINE-3) per 100 patient-years of exposure to brodalumab.Conclusions: Brodalumab treatment resulted in significant clinical improvements in patients with moderate-to-severe psoriasis. (Funded by Amgen; AMAGINE-2 and AMAGINE-3 ClinicalTrials.gov numbers, NCT01708603 and NCT01708629.). [ABSTRACT FROM AUTHOR]

Introduction: Risankizumab has demonstrated a favourable safety profile in patients with psoriatic disease (moderate-to-severe psoriasis [PsO] and psoriatic arthritis [PsA]). We evaluated the long-term safety of risankizumab in psoriatic disease., Methods: Long-term safety was evaluated by analysing data from 20 (phase 1-4) clinical trials for plaque PsO and four (phase 2-3) trials for PsA. Treatment-emergent adverse events (TEAEs) and AEs in areas of special interest were reported among patients receiving ≥ 1 dose of risankizumab. Exposure-adjusted event rates were presented as events (E) per 100 patient-years (PY)., Results: The long-term safety data analyses included 3658 patients with PsO (13,329.3 PY) and 1542 patients with PsA (3803.0 PY). The median (range) treatment duration for patients with PsO and PsA was 4.1 (0.2-8.8) years and 2.8 (0.2-4.0) years, respectively. In the PsO population, rates of TEAEs, serious AEs and AEs leading to discontinuation were 145.5 E/100 PY, 7.4 E/100 PY and 1.9 E/100 PY, respectively; in the PsA population, these rates were 142.6 E/100 PY, 8.6 E/100 PY, and 1.8 E/100 PY, respectively. The rates of serious infections (excluding COVID-19-related infections) in the PsO and PsA populations were 1.2 and 1.4 E/100 PY, respectively. The rates of opportunistic infections (excluding tuberculosis and herpes zoster) were low (< 0.1 E/100 PY) in both populations. The rates of both nonmelanoma skin cancer (NMSC) and malignant tumours excluding NMSC were 0.6 and 0.5 E/100 PY in PsO and PsA, respectively, which are within the benchmarks of prior epidemiological studies. Adjudicated major cardiovascular event rates were 0.5 E/100 PY in PsO and 0.3 E/100 PY in PsA, which are within the epidemiologic reference benchmarks for both indications. No additional safety concerns were identified with this long-term exposure., Conclusions: The results support the favourable safety profile of risankizumab for long-term treatment of psoriatic disease with no new safety concerns and similar safety profiles among both PsO and PsA populations., (© 2024. The Author(s).)

Psoriasis is a multifactorial, chronic inflammatory skin disease with unresolved questions on its primary events. Iron overload has been described in the epidermis of psoriasis patients, but its relevance remains unknown. We found that the key iron regulatory hormone hepcidin was highly expressed in the epidermis of psoriasis patients, especially the pustular variants resistant to treatments. In a murine model of acute skin inflammation, keratinocyte-derived hepcidin was required for iron retention in keratinocytes, leading to hyperproliferation of the epidermal layer and neutrophil recruitment, two main features of psoriatic skin lesions. Keratinocytes overexpressing hepcidin were sufficient to elicit these psoriasiform features in a transgenic mouse model. Furthermore, transcriptome analysis of these keratinocytes revealed canonical pathways found in human psoriasis, pointing to a causal role for hepcidin in the pathogenesis of the disease. Altogether, our data suggest that hepcidin could be an actionable target for skin psoriasis treatment, in addition to current therapeutics, or targeted as maintenance therapy during remission to prevent recurrence., (© 2024. The Author(s).)

EFFISAYIL 1 was a randomized, placebo-controlled study of spesolimab, an anti-IL-36 receptor antibody, in patients presenting with a generalized pustular psoriasis flare. Treatment with spesolimab led to more rapid pustular and skin clearance versus treatment with placebo in approximately half of the patients. In this study, we present histologic, transcriptomic, and proteomic analyses of lesional and nonlesional skin and whole-blood samples collected from EFFISAYIL 1. Treatment with spesolimab led to a transition toward a nonlesional profile, with a downregulation of gene expressions in the skin of IL-36 transcripts (IL36α, IL36β, IL36γ) and those associated with neutrophil recruitment (CXCL1, CXCL6, CXCL8), proinflammatory cytokines (IL6, IL19, IL20), and skin inflammation (DEFB4A, S100A7, S100A8). Changes were manifest at week 1 and sustained to week 8. At the systemic level, reductions in serum biomarkers of inflammation (IL-17, IL-8, IL-6) were sustained until 12 weeks after spesolimab treatment. Considerable overlap was observed in the spesolimab-induced changes in gene and protein expressions from skin and blood samples, demonstrating the molecular basis of the effects of spesolimab on controlling local and systemic inflammation. Data are consistent with the mode of action of spesolimab, whereby inhibition of the IL-36 pathway leads to subsequent reductions in the key local and systemic pathologic events associated with generalized pustular psoriasis flares., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Generalized pustular psoriasis (GPP) lacks internationally accepted definitions and diagnostic criteria, impeding timely diagnosis and treatment and hindering cross-regional clinical and epidemiological study comparisons., Objective: To develop an international consensus definition and diagnostic criteria for GPP using the modified Delphi method., Evidence Review: The rarity of GPP presents a challenge in acquiring comprehensive published clinical data necessary for developing standardized definition and criteria. Instead of relying on a literature search, 43 statements that comprehensively addressed the fundamental aspects of the definitions and diagnostic criteria for GPP were formulated based on expert reviews of 64 challenging GPP cases. These statements were presented to a panel of 33 global GPP experts for voting, discussion, and refinements in 2 virtual consensus meetings. Consensus during voting was defined as at least 80% agreement; the definition and diagnostic criteria were accepted by all panelists after voting and in-depth discussion., Findings: In the first and second modified Delphi round, 30 (91%) and 25 (76%) experts participated. In the initial Delphi round, consensus was achieved for 53% of the statements, leading to the approval of 23 statements that were utilized to develop the proposed definitions and diagnostic criteria for GPP. During the second Delphi round, the final definition established was, "Generalized Pustular Psoriasis is a systemic inflammatory disease characterized by cutaneous erythema and macroscopically visible sterile pustules." It can occur with or without systemic symptoms, other psoriasis types, and laboratory abnormalities. GPP may manifest as an acute form with widespread pustules or a subacute variant with an annular phenotype. The identified essential criterion was, "Macroscopically visible sterile pustules on erythematous base and not restricted to the acral region or within psoriatic plaques.", Conclusions and Relevance: The achievement of international consensus on the definition and diagnostic criteria for GPP underscores the importance of collaboration, innovative methodology, and expert engagement to address rare diseases. Although further validation is needed, these criteria can serve as a reference point for clinicians, researchers, and patients, which may contribute to more accurate diagnosis and improved management of GPP.

Background: GPP is a rare, chronic, neutrophilic skin disease, with limited real-world data characterizing patients with flares and the impact of flares on disease progression and morbidity., Objective: Describe the clinical characteristics of patients with GPP, comorbidities, disease epidemiology and frequency and severity of flares, and compare patients with GPP with a matched severe psoriasis population., Methods: In this population-based real-world cohort study an algorithm was developed to identify patients with GPP flares. Three cohorts were identified using the Système National des Données de Santé (SNDS) database covering almost the entire French population; a prevalent cohort (2010-2018), an incident cohort (2012-2015). A severe psoriasis cohort was compared with the GPP incident cohort using propensity score matching., Results: The prevalent and incident cohorts comprised 4195 and 1842 patients, respectively. In both cohorts, mean age was 58 years; 53% were male. Comorbidities were significantly more common in the incident cohort versus matched psoriasis cohort, respectively, including hypertension (44% vs. 26%), ischaemic heart disease (26% vs. 18%) and hyperlipidaemia (25% vs. 15%). In the incident cohort, the flare rate was 0.1 flares/person-year and 0.4 flares/person-year among the 569 out of 1842 patients hospitalized with flares. These patients had a mean (±SD) stay of 11.6 ± 10.4 days; 25% were admitted to the intensive care unit. In 2017, the cumulative incidence and cumulative GPP age-sex standardized prevalence were 7.1 and 45.2 per million, respectively., Conclusions: Patients with GPP had a distinct comorbidity profile compared to patients with severe psoriasis, and GPP flares were associated with long hospitalizations., (© 2024 Boehringer Ingelheim International GmbH and The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltdon behalf of European Academy of Dermatology and Venereology.)

Background: Psoriasis is an inflammatory skin disease that impacts a heterogeneous group of patients and can have multiple clinical manifestations. Risankizumab is approved for the treatment of moderate-to-severe plaque psoriasis., Objectives: To evaluate the long-term efficacy of risankizumab according to baseline patient characteristics, and for the treatment of high-impact disease manifestations (nail, scalp and palmoplantar psoriasis), through 256 weeks of continuous treatment in the phase 3 LIMMitless study., Methods: This subgroup analysis evaluated pooled data from patients with moderate-to-severe plaque psoriasis who were randomized to risankizumab 150 mg during two double-blind, phase 3, 52-week base studies (UltIMMa-1/2; NCT02684370/NCT02684357) and were enrolled in the phase 3 LIMMitless open-label extension study (NCT03047395). Subgroup assessments included the proportion of patients who achieved ≥90%/100% improvement in Psoriasis Area and Severity Index (PASI 90/100). Among patients with nail, scalp and/or palmoplantar psoriasis in addition to skin psoriasis, assessments included changes from baseline in and resolution of these three psoriatic manifestations., Results: Overall, a numerically similar proportion of patients (N = 525) achieved PASI 90/100 through Week 256, regardless of their baseline age, sex, body mass index, weight, PASI or psoriatic arthritis status. Patients with nail, scalp and/or palmoplantar psoriasis experienced substantial improvements in manifestation-specific indices (mean improvement from baseline to Week 256 of >81%, >94% and >97%, respectively); in patients with all three manifestations (N = 121), 44.6% achieved complete clearance of these manifestations at Week 256., Conclusions: Risankizumab demonstrated generally consistent efficacy through 256 weeks across patient subgroups and showed durable long-term efficacy for psoriatic disease manifestations., (© 2024 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.)

Tissue transcriptomics is used to uncover molecular dysregulations underlying diseases. However, the majority of transcriptomics studies focus on single diseases with limited relevance for understanding the molecular relationship between diseases or for identifying disease-specific markers. In this study, we used a normalization approach to compare gene expression across nine inflammatory skin diseases. The normalized datasets were found to retain differential expression signals that allowed unsupervised disease clustering and identification of disease-specific gene signatures. Using the NS-Forest algorithm, we identified a minimal set of biomarkers and validated their use as diagnostic disease classifier. Among them, PTEN was identified as being a specific marker for cutaneous lupus erythematosus and found to be strongly expressed by lesional keratinocytes in association with pathogenic type I IFNs. In fact, PTEN facilitated the expression of IFN-β and IFN-κ in keratinocytes by promoting activation and nuclear translocation of IRF3. Thus, cross-comparison of tissue transcriptomics is a valid strategy to establish a molecular disease classification and to identify pathogenic disease biomarkers., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about phototype and the response to systemic treatment in psoriasis., Objectives: To assess the characteristics of psoriasis, the therapeutic choice and its efficacy according to phototype., Methods: We included patients from the PsoBioTeq cohort initiating a first biologic. Patients were classified according to their phototype. The evaluation included disease characteristics, choice of the initial biologic and therapeutic response at 12 months based on 90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90) and Dermatology Life Quality Index (DLQI) 0/1., Results: Of the 1400 patients included, 423 (30.2%), 904 (64.6%) and 73 (5.2%) were in the phototype I-II, III-IV and V-VI groups, respectively. The V-VI group had a higher initial DLQI, and more frequently initiated ustekinumab. Patients in the V-VI group maintained the initial biologic prescribed as did the other phototype groups, even though the proportion of patients reaching PASI 90 and DLQI 0/1 at 12 months was lower in this group than the other groups., Conclusions: Patient phototype seems associated with quality of life and choice of the initial biologic in psoriasis. The phototype V-VI group less frequently switched treatments than did the other groups when the response was not efficient., Competing Interests: Conflicts of interest F.T. is Head of the Clinical Research Unit at Pitié-Salpêtrière Hospital and the Centre de Pharmacoepidemiologie (Cephepi) (Pharmacoepidemiology Centre) of the Assistance Publique–Hôpitaux de Paris (Paris Hospitals); she has received research funding, grants and fees for consultancy activities from a large number of pharmaceutical companies that have contributed to employee salaries (but no personal remuneration for F.T.). M.V. has undertaken activities as a paid consultant, advisor or speaker for AbbVie, Arrow, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Galderma, Janssen, LEO Pharma, Lilly, medac, MSD, Novartis and Pfizer. M.B.-B. offers a consultancy service and is an investigator for AbbVie, Amgen, Celgene, Janssen, LEO Pharma, Lilly, MSD, Novartis and Pfizer. N.B. has been an investigator for Novartis and Pfizer; she is a consultant for Janssen and has received speaker remuneration from Janssen. P.J. is a consultant for GSK, Lilly, Principia Biopharma, Roche and Sanofi Aventis. D.J. is a consultant for AbbVie, Biogen, Celgene, Fresenius Kabi, Janssen, Lilly, medac, Merck Sharp & Dohme, Novartis, Pfizer and UCB. E.M. is a consultant for AbbVie, Janssen, Novartis and Pfizer; she has also been an investigator for AbbVie, Amgen, AstraZeneca, LEO Pharma, Novartis and Pfizer; and has received speaker remuneration from AbbVie, Janssen, Novartis and Pfizer. C.P. has been an investigator and consultant for AbbVie, Amgen, Boehringer Ingelheim, Celgene, GSK, Janssen, LEO Pharma, Lilly, Novartis and Pfizer. M.-A.R. is a consultant for AbbVie, BMS, Galderma, Janssen, LEO Pharma, Merck, Novartis, Pfizer and Pierre Fabre. H.B. has undertaken activities as a paid consultant, advisor or speaker for AbbVie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sun Pharmaceuticals and UCB; he has also received grant funding from Pfizer. The other authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Conflicts of interest The full list is provided in Appendix S1 (see Supporting Information).

Background: Effisayil 1 was a randomized, placebo-controlled study of spesolimab, which is an anti-IL-36 receptor antibody, in patients presenting with a generalized pustular psoriasis flare., Objective: To assess the effects of spesolimab over the 12-week study., Methods: The primary endpoint of the study was Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at week 1. Patients (N = 53) were randomized (2:1) to receive a single intravenous dose of 900 mg spesolimab or placebo on day 1. Patients could receive open-label spesolimab for persistent flare symptoms on day 8., Results: Most patients receiving spesolimab achieved a GPPGA pustulation subscore of 0 (60.0%) and GPPGA total score of 0 or 1 (60.0%) by week 12. In patients randomized to placebo who received open-label spesolimab on day 8, the proportion with GPPGA pustulation subscore of 0 increased from 5.6% at day 8 to 83.3% at week 2. No factors predictive of spesolimab response were identified in patient demographics or clinical characteristics., Limitations: The effect of initial randomization was not determined conventionally beyond week 1 due to patients receiving open-label spesolimab., Conclusion: Rapid control of generalized pustular psoriasis flare symptoms with spesolimab was sustained over 12 weeks, further supporting its potential use as a therapeutic option for patients., Competing Interests: Conflicts of interest The authors met the criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive payments related to the development of this manuscript. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. Dr Elewski is an investigator for AbbVie, Amgen (previously Celgene), AnaptysBio, Bausch Health (formerly Valeant Pharmaceuticals), Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Incyte, LEO Pharma, Menlo, Merck, Novartis, Pfizer, Regeneron, Sun Pharmaceutical Industries, UCB, and Vanda; and is a consultant for Amgen (previously Celgene), Arcutis, Bausch Health (formerly Valeant Pharmaceuticals), Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, LEO Pharma, Novartis, and UCB. Dr Lebwohl is an employee of Mount Sinai and receives research funds from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron, and UCB, Inc.; and is a consultant for Aditum Bio, Almirall, AltruBio Inc., AnaptysBio, Arcutis, Arena Pharmaceuticals, Aristea Therapeutics, Avotres Therapeutics, BiomX, Brickell Biotech, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Celltrion, CorEvitas, Dermavant Sciences, Evommune, Inc., Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Hexima Ltd., Incyte, LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, Trevi, Vial, and Verrica. Dr Anadkat declares paid activities as a current advisor or consultant for BioLinq, Boehringer Ingelheim, Eli Lilly, Novocure, Protagonist, and Springworks; has served as prior consultant or advisor for AbbVie, Adgero, Amgen, Aspire Bariatrics, AstraZeneca, Biogen, Bristol Myers Squibb, ImClone, Innovaderm, OnQuality, Therakos, Veloce, and UCB; and has served as an investigator for AbbVie, AnaptysBio, Biogen, Boehringer Ingelheim, ChemoCentryx, Eli Lilly, Incyte, InflaRx, Hana Biosciences, Lutris, Moonlake, Novartis, OnQuality, UCB, Veloce, XBiotech, and Xoma. Prof Barker declares having attended advisory boards and/or received consultancy fees and/or spoken at sponsored symposia and/or received grant funding from AbbVie, Almirall, Amgen, AnaptysBio, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Samsung, Sienna, Sun Pharmaceutical Industries, and UCB. Prof Ghoreschi declares having attended advisory boards and/or received consultancy fees and/or spoken at sponsored symposia and served as an investigator for AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis, Pfizer, and UCB. Prof Imafuku has served as a consultant and/or paid speaker for and/or accepted a research grant from and/or participated in clinical trials sponsored by companies including AbbVie, Amgen, Eisai, Eli Lilly, Janssen, Kyowa Kirin, LEO Pharma, Maruho Pharmaceutical, Mitsubishi Tanabe, Novartis, Sun Pharmaceutical Industries, Taiho Yakuhin Koryo, Torii Yakuhin, and UCB. Prof Mrowietz has been an advisor and/or received speaker’s honoraria and/or received grants and/or participated in clinical trials for AbbVie, Aditxt, Almirall, Amgen (previously Celgene), Aristea, Boehringer Ingelheim, Bristol Myers Squibb, Dr. Reddy’s Laboratories, Eli Lilly, Foamix, Formycon, Immunic, Janssen, LEO Pharma, Medac, MetrioPharm, Novartis, Phi-Stone, Pierre Fabre, Sanofi Aventis, and UCB. Li, Quaresma, and Dr Thoma are employees of Boehringer Ingelheim. Prof Bachelez reports receiving grants or contracts from Boehringer Ingelheim, Bristol Myers Squibb, Janssen, LEO Pharma, Novartis, and Pfizer; consulting fees from AbbVie, Almirall, Anaptysbio, Aristea Therapeutics, Biocad, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermavant, Innovaderm, Janssen, Kyowa Kirin, LEO Pharma, Lilly, Mylan, Novartis, UCB, and Xion Pharmaceuticals; honoraria from AbbVie, Boehringer Ingelheim, Celgene, and LEO Pharma; advisory board participation for Avillion; and meeting attendance support from Janssen, Novartis, and UCB., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Generalized pustular psoriasis (GPP) is a rare and life-threatening skin disease often accompanied by systemic inflammation. There are currently no standardized or validated GPP-specific measures for assessing severity., Objective: To evaluate the reliability, validity and responder definitions of the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) and Generalized Pustular Psoriasis Area and Severity Index (GPPASI)., Methods: The GPPGA and GPPASI were validated using outcome data from Week 1 of the Effisayil™ 1 study. The psychometric analyses performed included confirmatory factor analysis, item-to-item/item-to-total correlations, internal consistency reliability, test-retest reliability, convergent validity, known-groups validity, responsiveness analysis and responder definition analysis., Results: Using data from this patient cohort (N = 53), confirmatory factor analysis demonstrated unidimensionality of the GPPGA total score (root mean square error of approximation <0.08), and GPPGA item-to-item and item-to-total correlations ranged from 0.58 to 0.90. The GPPGA total score, pustulation subscore and GPPASI total score all demonstrated good test-retest reliability (intraclass correlation coefficient: 0.70, 0.91 and 0.95 respectively), and good evidence of convergent validity. In anchor-based analyses, all three scores were able to detect changes in symptom and disease severity over time; reductions of -1.4, -2.2 and - 12.0 were suggested as clinically meaningful improvement thresholds for the GPPGA total score, GPPGA pustulation subscore and GPPASI total score respectively. Anchor-based analyses also supported the GPPASI 50 as a clinically meaningful threshold for improvement., Conclusions: Overall, our findings indicate that the GPPGA and GPPASI are valid, reliable and responsive measures for the assessment of GPP disease severity, and support their use in informing clinical endpoints in trials in GPP., (© 2023 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.)

Lichen planus (LP) is a cutaneomucosal chronic inflammatory disease characterized by a CD8 + cytotoxic T-lymphocytes (CTL) infiltrate. In erosive oral LP, we found HPV16-specific activated CTL in lesions, supporting a pathogenic contribution of HPV16. Here, we investigated whether a similar scenario occurs in other clinical forms of LP and in lichen sclerosus et atrophicus (LSA), another chronic disease also affecting the mucosa and/or the skin. Blood CTL from LP and LSA patients expressed significant higher levels of granzyme B, perforin and CD107a proteins than healthy donors. Expansions of TCRVß3 + CTL, with presence of TCR clonotypes identical to those previously detected in erosive oral LP, were found both in blood and mucosal/skin lesions of LP, and not of LSA patients. These expansions were enriched with HPV16-specific CD8 + T-cells as shown by their recognition of the E7 11-20 immunodominant epitope. In LSA patients, the peripheral repertoire of CTL was oligoclonal for TCRVß6 + CTL. Finally, although patients with LP and LSA have developed antibodies against HPV16 capsid L1, antibodies against HPV16 E6 were only observed in patients with LP. Overall, our data collectively suggest an involvement of HPV16-specific CTL in different clinical forms of LP, not only in erosive oral LP, while a different scenario operates in LSA., (© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Dupilumab is a therapeutic antibody targeting IL-4 and IL-13 receptor subunit alpha used for the treatment of patients with atopic dermatitis (AD). Cases of psoriasis-like reactions induced under dupilumab treatment (dupilumab-induced psoriatic eruption [DI-Pso]) for AD were recently reported. To understand the pathogenesis of DI-Pso, we performed gene expression profiling studies on skin biopsies of DI-Pso (n = 7) compared with those of plaque psoriasis, AD, and healthy controls (n = 4 each). Differential gene expression was performed using enrichment and Gene Ontology analysis. Gene expression was validated by qPCR, and protein levels were assessed by immunohistochemistry. Transcriptomic and protein analysis of DI-Pso compared with that of healthy controls, plaque psoriasis, and AD skins revealed activation of T helper 17/IL-23 pathways associated with a significant expression of IL-36, surrogate marker of pustular psoriasis. By contrast, T helper 2 representative genes' expression was strongly decreased in DI-Pso across comparison. Matching analysis with public data of pustular psoriasis skin corroborated that DI-Pso and pustular psoriasis upstream regulators overlap, greater than the overlap with plaque psoriasis. Furthermore, DI-Pso showed strongly decreased expression of many barrier skin genes compared with healthy controls, plaque psoriasis, and AD. Our data indicate that the pathogenesis of DI-Pso relied on a shift of skin immune responses from a T helper 2 to an IL-36 and T helper 17 polarization and on intensified skin barrier alterations., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Nonadherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association between mental health and nonadherence to immune-modifying therapy during the pandemic., Objectives: To assess the extent of and reasons underlying nonadherence to systemic immune-modifying therapy during the COVID-19 pandemic in individuals with psoriasis, and the association between mental health and nonadherence., Methods: Online self-report surveys (PsoProtectMe), including validated screens for anxiety and depression, were completed globally during the first year of the pandemic. We assessed the association between anxiety or depression and nonadherence to systemic immune-modifying therapy using binomial logistic regression, adjusting for potential cofounders (age, sex, ethnicity, comorbidity) and country of residence., Results: Of 3980 participants from 77 countries, 1611 (40.5%) were prescribed a systemic immune-modifying therapy. Of these, 408 (25.3%) reported nonadherence during the pandemic, most commonly due to concerns about their immunity. In the unadjusted model, a positive anxiety screen was associated with nonadherence to systemic immune-modifying therapy [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.07-1.76]. Specifically, anxiety was associated with nonadherence to targeted therapy (OR 1.41, 95% CI 1.01-1.96) but not standard systemic therapy (OR 1.16, 95% CI 0.81-1.67). In the adjusted model, although the directions of the effects remained, anxiety was not significantly associated with nonadherence to overall systemic (OR 1.20, 95% CI 0.92-1.56) or targeted (OR 1.33, 95% CI 0.94-1.89) immune-modifying therapy. A positive depression screen was not strongly associated with nonadherence to systemic immune-modifying therapy in the unadjusted (OR 1.22, 95% CI 0.94-1.57) or adjusted models (OR 1.14, 95% CI 0.87-1.49)., Conclusions: These data indicate substantial nonadherence to immune-modifying therapy in people with psoriasis during the pandemic, with attenuation of the association with mental health after adjusting for confounders. Future research in larger populations should further explore pandemic-specific drivers of treatment nonadherence. Clear communication of the reassuring findings from population-based research regarding immune-modifying therapy-associated adverse COVID-19 risks to people with psoriasis is essential, to optimize adherence and disease outcomes., Competing Interests: Conflict of interests J.W. has presented talks for Abbott, AbbVie, Bayer, Boehringer Ingelheim, Chiesi, Merck and Roche. K.J.M. reports personal fees from LEO Pharma and Novartis, outside the submitted work. H.M. reports grants from AbbVie, Almirall, Celgene, Dermal Laboratories, Eli Lilly, Janssen, LEO Pharma, T & R Derma and UCB, outside the submitted work. D.U. reports grants from AbbVie, Almirall, Amgen, Celgene, Dermal Laboratories, Eli Lilly, Janssen, LEO Pharma, T & R Derma and UCB, outside the submitted work. L.M. reports personal fees from AbbVie, Celgene, Janssen, LEO Pharma, Novartis and UCB, outside the submitted work. Additional disclosures from L.M. include Almirall, BMS and Lilly. H.B. reports personal fees from AbbVie, Almirall, Biocad, Boehringer-Ingelheim, Janssen, Kyowa Kirin, LEO Pharma, Novartis, Pfizer and UCB, outside the submitted work. F.C. reports consultancy fees from AnaptysBio, grants from Boehringer Ingelheim, outside the submitted work. C.D.l.C. reports personal fees from Boehringer Ingelheim and UCB Pharma; grants from Janssen, Pfizer, Sandoz, Sanofi; grants and personal fees from AbbVie, Novartis, outside the submitted work. P.D.M. reports grants and personal fees from UCB; personal fees from Janssen and Novartis, outside the submitted work. P.G. reports personal fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pierre Fabre, Sandoz and UCB, outside the submitted work. D.J. reports personal fees and nonfinancial support from AbbVie, Celgene, Janssen-Cilag, Lilly, LEO Pharma, MEDAC and Novartis; and personal fees from Amgen, outside the submitted work. L.P. reports grants and personal fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Janssen, Lilly, Novartis and UCB; and personal fees from Bristol Myers Squibb, Fresenius-Kabi, Mylan, Pfizer, Samsung-Bioepis, Sandoz, Sanofi, outside the submitted work. P.S. has done consultancies in the past for Sanofi 111017 and AbbVie 041217 (unpaid); has received departmental independent research grants for TREAT NL registry from pharma companies since December 2019; is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of diseases such as psoriasis and atopic dermatitis, for which financial compensation is paid to the department/hospital; and is chief investigator of the systemic and phototherapy atopic eczema registry (TREAT NL) for adults and children, as well as one of the main investigators of the SECURE-AD registry. T.T. reports grants and personal fees from AbbVie, Almirall, Amgen, Arena Pharmaceuticals, Biocad, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Samsung-Bioepis and Sandoz, during the conduct of the study. R.B.W. reports grants from AbbVie, Almirall, Amgen, Celgene, Janssen, LEO, Lilly, Medac, Novartis, Pfizer and UCB. R.B.W. also reports consultancy fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, GSK, Janssen, LEO, Lilly, Medac, Novartis, Pfizer, Sanofi, Sun Pharma, UCB and UNION. H.W. is on the Board of the International Federation of Psoriasis Associations who have received grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sun Pharma and UCB, outside the submitted work. J.B.G. reports personal fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi and UCB, outside the submitted work. C.E.M.G. reports grants and personal fees from AbbVie, Janssen, Lilly and Novartis and UCB Pharma; and grants from Almirall, Amgen, BMS, LEO and Pfizer, outside the submitted work. J.N.B. reports grants and personal fees from AbbVie, J&J, Lilly and Novartis during the conduct of the study. J.N.B. has attended advisory boards, and/or received consultancy fees, and/or spoken at sponsored symposia, and/or received grant funding from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Samsung, Sun Pharma and UCB. C.H.S. reports grants from AbbVie, Novartis, Pfizer and Sanofi; and through consortia with multiple academic partners (psort.org.uk, BIOMAP-IMI.eu), outside the submitted work. S.K.M. reports departmental income from AbbVie, Almirall, Eli Lilly, Janssen-Cilag, Novartis, Sanofi and UCB, outside the submitted work., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Competing Interests: Conflicts of interest: M.B.-B. is a consultant for AbbVie, Celgene, Janssen-Cilag, Lilly, Novartis, Medac and UCB. N.B. is a consultant for Novartis, Celgene, MSD, Janssen, Lilly, Pfizer and AbbVie. P.J. is a consultant for AbbVie, Celgene, Janssen-Cilag, Lilly and Novartis. D.J. is a consultant for AbbVie, Amgen, Celgene, Fresenius-Kabi, Janssen-Cilag, LEO, Lilly, Pfizer, MEDAC, Novartis and UCB. E.M. is a consultant for AbbVie, LEO Pharma, Celgene, Pfizer, Janssen-Cilag and Novartis. C.P. is a consultant for AbbVie, Almirall, Amgen, Boerhinger, Celgene, Janssen-Cilag, LEO Pharma, Lilly, Pfizer, Novartis, Pierre Fabre, Sanofi and UCB. M.-A.R. is a consultant for AbbVie, Amgen, Boehringer, Celgene, Janssen-Cilag, LEO Pharma, Lilly, Nordic, Novartis, Pfizer and Medac. H.B. is a consultant for AbbVie, Almirall, Amgen, Biocad, Boerhinger, Celgene, Dermavant, Janssen, LEO Pharma, Eli Lilly, Mylan, Novartis, Pfizer, Pierre Fabre, Sun Pharmaceuticals and UCB. H.A. is a consultant for AbbVie, Novartis, Janssen-Cilag, Almirall, Leo and Lilly.

Background: Generalized pustular psoriasis (GPP) is a rare, neutrophilic skin disease that can become life-threatening if flares are untreated. There are limited data describing the characteristics and clinical course of GPP disease flares with current treatment options., Objective: The aim of the study was to describe the characteristics and outcomes of GPP flares using historical medical information from patients enrolled in the Effisayil™ 1 trial., Methods: Investigators collected retrospective medical data characterizing patients' GPP flares prior to clinical trial enrollment. Data on overall historical flares were collected, as well as information on patients' typical, most severe, and longest past flares. This included data on systemic symptoms, flare duration, treatment, hospitalization, and time to clearance of skin lesions., Results: In this cohort (N = 53), patients with GPP experienced a mean of 3.4 flares per year. Flares were painful, associated with systemic symptoms, and often triggered by stress, infections, or treatment withdrawal. Resolution of flares was longer than 3 weeks in 57.1%, 71.0%, and 85.7% of documented (or identified) typical, most severe, and longest flares, respectively. GPP flares led to patient hospitalization in 35.1%, 74.2%, and 64.3% of patients for their typical, most severe, and longest flares, respectively. For the majority of patients, pustules took up to 2 weeks to clear for a typical flare and 3-8 weeks to clear for the most severe and longest flares., Conclusion: Our findings highlight that current treatment options are slow to control GPP flares and provide context for assessing the efficacy of new therapeutic strategies in patients with a GPP flare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Generalized pustular psoriasis (GPP) is a rare autoinflammatory skin disease characterized by flares of widespread erythema with sterile pustules, and can be relapsing with recurrent flares, or persistent with intermittent flares. Spesolimab, a humanized anti-interleukin-36 (IL-36) receptor monoclonal antibody, targets the key IL-36 pathogenetic pathway in GPP. A previous study showed that spesolimab treatment led to rapid pustular and skin clearance in patients with GPP flares, which was sustained for up to 12 weeks. This study investigates the long-term effects of spesolimab on GPP flares, for which no specific treatments are currently available. The Effisayil™ 2 study will assess whether maintenance treatment with subcutaneous spesolimab prevents the occurrence of GPP flares and determine the optimal dosing regimen to achieve this aim., Methods: Patients will have a documented history of GPP with a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score of 0 or 1 (clear or almost clear) at screening and randomization. Patients will be randomized 1:1:1:1 to three groups receiving a 600-mg subcutaneous loading dose of spesolimab followed by a 300-mg maintenance dose administered every 4 or 12 weeks, or a 300-mg loading dose followed by a 150-mg maintenance dose administered every 12 weeks, and one group receiving placebo, for 48 weeks. The primary endpoint is time to first GPP flare. If a patient experiences a GPP flare during the randomized maintenance treatment period, an open-label intravenous dose of 900-mg spesolimab will be administered, with an option for a second intravenous dose after 1 week., Conclusions: Effisayil™ 2 is the first placebo-controlled study in patients with GPP to investigate whether maintenance treatment with spesolimab can prevent flares and provide sustained disease control. This study will provide valuable insights on the long-term management of patients with this potentially life-threatening skin disease., Trial Registration Number: NCT04399837., (© 2022. The Author(s).)

Background: The COVID-19 pandemic has raised questions regarding the management of chronic skin diseases, especially in patients on systemic treatments. Data concerning the use of biologics in adults with psoriasis are reassuring, but data specific to children are missing. Moreover, COVID-19 could impact the course of psoriasis in children., Objectives: The aim of this study was therefore to assess the impact of COVID-19 on the psoriasis of children, and the severity of the infection in relation to systemic treatments., Methods: We set up an international registry of paediatric psoriasis patients. Children were included if they were under 18 years of age, had a history of psoriasis, or developed it within 1 month of COVID-19 and had COVID-19 with or without symptoms., Results: One hundred and twenty episodes of COVID-19 in 117 children (mean age: 12.4 years) were reported. The main clinical form of psoriasis was plaque type (69.4%). Most children were without systemic treatment (54.2%); 33 (28.3%) were on biologic therapies, and 24 (20%) on non-biologic systemic drugs. COVID-19 was confirmed in 106 children (88.3%) and 3 children had two COVID-19 infections each. COVID-19 was symptomatic for 75 children (62.5%) with a mean duration of 6.5 days, significantly longer for children on non-biologic systemic treatments (P = 0.02) and without systemic treatment (P = 0.006) when compared with children on biologics. The six children who required hospitalization were more frequently under non-biologic systemic treatment when compared with the other children (P = 0.01), and particularly under methotrexate (P = 0.03). After COVID-19, the psoriasis worsened in 17 cases (15.2%). Nine children (8%) developed a psoriasis in the month following COVID-19, mainly a guttate form (P = 0.01)., Discussion: Biologics appear to be safe with no increased risk of severe form of COVID-19 in children with psoriasis. COVID-19 was responsible for the development of psoriasis or the worsening of a known psoriasis for some children., (© 2022 European Academy of Dermatology and Venereology.)

Introduction: Generalized pustular psoriasis (GPP) is a rare, severe, clinically heterogeneous disease characterized by flares of widespread, noninfectious, macroscopically visible pustules that occur with or without systemic inflammation, and are associated with significant morbidity and mortality. Historically, GPP has been classified as a variant of psoriasis vulgaris (PV, or plaque psoriasis); however, accumulating evidence indicates that these are distinct conditions, requiring different treatment approaches., Areas Covered: In this perspective article we review evidence that supports the classification of GPP as distinct from PV., Expert Opinion: The histopathologic and clinical appearance of GPP is distinct from that of PV and fundamental differences exist between the two conditions in terms of genetic causes and expression-related mechanisms of disease development. GPP results from dysregulation of the innate immune system, with disruption of the interleukin (IL)-36 inflammatory pathway, induction of inflammatory keratinocyte responses, and recruitment of neutrophils. PV is driven by the adaptive immune system, with a key role played by IL-17. Considering GPP as a separate disease will enable greater focus on its specific pathogenesis and the needs of patients. Many treatments for PV have insufficient efficacy in GPP and a therapeutic approach developed specifically for GPP might lead to better patient outcomes.

Paediatric psoriasis has been associated with school absenteeism, limitation of physical activities, psychiatric disorders and, in the longer term, with sexual dysfunction and addictions. This raises the hypothesis that childhood onset psoriasis may affect patients' educational development, and further social and professional outcomes. This study evaluated the relationship between childhood onset psoriasis and patients' educational and socioeconomic characteristics, and the development of addictions in adulthood. This cross-sectional ancillary study captured patients' characteristics at baseline in the French PSOBIOTEQ registry. Data in adulthood included: educational (baccalaureate) and socioeconomic (working activity) groups, smoking status (self-reporting of being a current smoker vs past smoker or non-smoker), alcohol consumption (defined as at least 1 glass of alcoholic beverage per day), and living conditions (alone/family/social institutions; child at home). A total of 1,960 patients were included, of whom 26.2% had childhood onset psoriasis. In multivariate analyses, childhood onset psoriasis was associated with smoker status (p = 0.02). No association was observed with educational level, working activity, living conditions, or alcohol consumption. This study provides reassuring data overall with regard to the impact of childhood onset psoriasis on major social outcomes. Evidence for some association with addictive behaviours paves the way for larger prospective studies assessing in depth the social and educational impact of this disease.

Background: The IL-36 pathway plays a key role in the pathogenesis of generalized pustular psoriasis (GPP). In a proof-of-concept clinical trial, treatment with spesolimab, an anti-IL-36 receptor antibody, resulted in rapid skin and pustular clearance in patients presenting with GPP flares., Objective: We sought to compare the molecular profiles of lesional and nonlesional skin from patients with GPP or palmoplantar pustulosis (PPP) with skin from healthy volunteers, and to investigate the molecular changes after spesolimab treatment in the skin and blood of patients with GPP flares., Methods: Pre- and post-treatment skin and blood samples were collected from patients with GPP who participated in a single-arm, phase I study (n = 7). Skin biopsies from patients with PPP (n = 8) and healthy volunteers (n = 16) were obtained for comparison at baseline. Biomarkers were assessed by RNA-sequencing, histopathology, and immunohistochemistry., Results: In GPP and PPP lesions, 1287 transcripts were commonly upregulated or downregulated. Selected transcripts from the IL-36 signaling pathway were upregulated in untreated GPP and PPP lesions. In patients with GPP, IL-36 pathway-related signatures, T H 1/T H 17 and innate inflammation signaling, neutrophilic mediators, and keratinocyte-driven inflammation pathways were downregulated by spesolimab as early as week 1. Spesolimab also decreased related serum biomarkers and cell populations in the skin lesions from patients with GPP, including CD3 + T, CD11c + , and IL-36γ + cells and lipocalin-2-expressing cells., Conclusions: In patients with GPP, spesolimab showed rapid modulation of commonly dysregulated molecular pathways in GPP and PPP, which may be associated with improved clinical outcomes., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Drug survival reflects treatment effectiveness and safety in real life. There is limited data on the variation of drug survival with the availability of systemic treatments with additional biological disease-modifying antirheumatic drugs (bDMARDs) or synthetic disease-modifying antirheumatic drugs (sDMARDs). The aim of this study was to determine whether the increasing number of available systemic treatments for psoriasis affects drug survival over time. Patients were selected from the PsoBioTeq cohort, a French prospective observational cohort enrolling patients with moderate to severe psoriasis. All patients initiating a first bDMARD or sDMARD were included. The primary outcome was comparison of drug survival over time. A multivariate Cox proportional hazard ratio model was computed. A total of 1,866 patients were included; 739 females (39%), median age 47 years. In the multivariate Cox model, no association was found between the calendar year of initiation and drug survival (hazard ratio) overlapping from 0.80 (0.42-1.52) to 1.17 (0.64-2.17), p = 0.633). In conclusion, drug survival in psoriasis is not affected by the year of initiation.

Background: Risankizumab has demonstrated efficacy and safety in patients with moderate-to-severe plaque psoriasis in randomized clinical trials., Objectives: To evaluate safety data from risankizumab psoriasis phase I-III clinical trials., Methods: Short-term safety (through week 16) was analysed using integrated data from five phase II and III clinical trials. Long-term safety was evaluated using integrated data from 17 phase I-III completed and ongoing trials., Results: Short-term safety analyses included 1306 patients receiving risankizumab 150 mg and 300 patients receiving placebo [402·2 and 92·0 patient-years (PY) of exposure, respectively]. Long-term analyses included 3072 risankizumab-treated patients (exposure: 7927 PY). The median (excluding four outliers) treatment duration was 2·9 years (range 2 days to 5·9 years). Exposure-adjusted adverse event rates did not increase with long-term treatment (318 vs. 171 events per 100 PY for short- and long-term analyses). With long-term risankizumab treatment, rates of serious adverse events were 7·8 per 100 PY, serious infections 1·2 per 100 PY, nonmelanoma skin cancer (NMSC) 0·7 per 100 PY, malignant tumours excluding NMSC 0·5 per 100 PY, and adjudicated major adverse cardiovascular events 0·3 per 100 PY, with no important identified risks. Limitations include that the study inclusion and exclusion criteria varied and that three studies enrolled ≤ 50 patients., Conclusions: Risankizumab demonstrated a favourable safety profile over short- and long-term treatment in patients with moderate-to-severe psoriasis., (© 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Psoriasis is a chronic inflammatory skin disease that has a profound effect on health-related quality of life (HRQoL). Patient education programmes may help patients to gain life-long control over their chronic disease., Objective: This multicentre randomised controlled study evaluated whether a standardised multidisciplinary education programme was beneficial to psoriasis patients., Methods: Adults with moderate-to-severe psoriasis were randomly assigned (1:1) to an intervention group to receive an educational programme or to a control group to receive usual care. Randomization was stratified by previous treatment history. The primary outcome was HRQoL, assessed by scoring the Skindex-29 domains emotion, symptom, and functioning. Psoriasis severity was assessed using the psoriasis area severity index (PASI). Levels of perceived stress, patient knowledge about psoriasis, and patient satisfaction were also assessed. Follow-up evaluations were performed at 3, 6, and 12 months., Results: A total 142 patients formed the intention-to-treat population: 70 in the control group and 72 in the intervention group. Skindex component scores and the PASI were significantly lower at 3, 6, and 12 months as compared to baseline in both groups, but no significant differences were found between the groups. Knowledge about psoriasis improved significantly during follow-up amongst patients from the intervention group compared to controls (68% of correct answers vs. 56%; p < 0.01). Patient satisfaction with psoriasis management and treatment was also better in the intervention group., Conclusions: The standardised education programme did not improve HRQoL and disease severity in psoriasis, but led to a significant improvement in patient knowledge about the disease and increased patient satisfaction., (© 2021 S. Karger AG, Basel.)

Background: Generalized pustular psoriasis (GPP) is a rare, life-threatening, inflammatory skin disease characterized by widespread eruption of sterile pustules. Interleukin-36 signaling is involved in the pathogenesis of this disorder. Spesolimab, a humanized anti-interleukin-36 receptor monoclonal antibody, is being studied for the treatment of GPP flares., Methods: In a phase 2 trial, we randomly assigned patients with a GPP flare in a 2:1 ratio to receive a single 900-mg intravenous dose of spesolimab or placebo. Patients in both groups could receive an open-label dose of spesolimab on day 8, an open-label dose of spesolimab as a rescue medication after day 8, or both and were followed to week 12. The primary end point was a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (range, 0 [no visible pustules] to 4 [severe pustulation]) at the end of week 1. The key secondary end point was a GPPGA total score of 0 or 1 (clear or almost clear skin) at the end of week 1; scores range from 0 to 4, with higher scores indicating greater disease severity., Results: A total of 53 patients were enrolled: 35 were assigned to receive spesolimab and 18 to receive placebo. At baseline, 46% of the patients in the spesolimab group and 39% of those in the placebo group had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4. At the end of week 1, a total of 19 of 35 patients (54%) in the spesolimab group had a pustulation subscore of 0, as compared with 1 of 18 patients (6%) in the placebo group (difference, 49 percentage points; 95% confidence interval [CI], 21 to 67; P<0.001). A total of 15 of 35 patients (43%) had a GPPGA total score of 0 or 1, as compared with 2 of 18 patients (11%) in the placebo group (difference, 32 percentage points; 95% CI, 2 to 53; P = 0.02). Drug reactions were reported in 2 patients who received spesolimab, in 1 of them concurrently with a drug-induced hepatic injury. Among patients assigned to the spesolimab group, infections occurred in 6 of 35 (17%) through the first week; among patients who received spesolimab at any time in the trial, infections had occurred in 24 of 51 (47%) at week 12. Antidrug antibodies were detected in 23 of 50 patients (46%) who received at least one dose of spesolimab., Conclusions: In a phase 2 randomized trial involving patients with GPP, the interleukin-36 receptor inhibitor spesolimab resulted in a higher incidence of lesion clearance at 1 week than placebo but was associated with infections and systemic drug reactions. Longer and larger trials are warranted to determine the effect and risks of spesolimab in patients with pustular psoriasis. (Funded by Boehringer Ingelheim; Effisayil 1 ClinicalTrials.gov number, NCT03782792.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: The outbreak of chilblain-like lesions (CLL) during the COVID-19 pandemic has been reported extensively, potentially related to SARS-CoV-2 infection, yet its underlying pathophysiology is unclear., Objectives: To study skin and blood endothelial and immune system activation in CLL in comparison with healthy controls and seasonal chilblains (SC), defined as cold-induced sporadic chilblains occurring during 2015 and 2019 with exclusion of chilblain lupus., Methods: This observational study was conducted during 9-16 April 2020 at Saint-Louis Hospital, Paris, France. All patients referred with CLL seen during this period of the COVID-19 pandemic were included in this study. We excluded patients with a history of chilblains or chilblain lupus. Fifty patients were included., Results: Histological patterns were similar and transcriptomic signatures overlapped in both the CLL and SC groups, with type I interferon polarization and a cytotoxic-natural killer gene signature. CLL were characterized by higher IgA tissue deposition and more significant transcriptomic activation of complement and angiogenesis factors compared with SC. We observed in CLL a systemic immune response associated with IgA antineutrophil cytoplasmic antibodies in 73% of patients, and elevated type I interferon blood signature in comparison with healthy controls. Finally, using blood biomarkers related to endothelial dysfunction and activation, and to angiogenesis or endothelial progenitor cell mobilization, we confirmed endothelial dysfunction in CLL., Conclusions: Our findings support an activation loop in the skin in CLL associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestations., (© 2021 British Association of Dermatologists.)