SummaryBackground Pyoderma gangrenosum (PG) is a rare, neutrophilic, ulcerative skin disease that is difficult to treat, especially when unresponsive to steroids. Objectives To determine whether canakinumab is an effective and safe treatment in PG. Methods Five adult patients with clinically and histologically confirmed steroidrefractory PG were enrolled in this prospective open-label study. They received canakinumab 150 mg subcutaneously at week 0 with an optional 150 mg at week 2 in case of an inadequate response [Physician's Global Assessment (PGA) ≥ 2], and an optional 150-300 mg at week 8 depending on PGA. The primary clinical end point was clinical improvement (PGA at least À1 from baseline) and/or complete remission (PGA 0 or 1) at week 16. Real-time quantitative polymerase chain reaction was performed on skin samples to quantify cytokine mRNA levels. Results Interleukin (IL)-1b and its known target genes IL6, CXCL8 and IL36A were significantly increased in lesional skin of PG. Under canakinumab therapy, four of five patients showed a decrease in target-lesion size, PGA and Dermatology Life Quality Index (DLQI), and three of five achieved complete remission. The mean diameter of target lesions decreased from 4Á32 AE 2Á6 cm at visit 1 to 0Á78 AE 1Á3 cm at visit 7 (P = 0Á03). Mean DLQI decreased from 15 AE 5 at visit 1 to 8 AE 4 by visit 7 (P = 0Á01). Adverse effects were reported in two patients: fatigue in one and worsening of disease at a nontarget lesion in the other. Conclusions Our data indicate that IL-1b plays a key pathogenic role in PG and canakinumab may represent a therapeutic option for steroid-refractory PG.

Background Use of Janus kinase 1 inhibitors in moderate‐to‐severe atopic dermatitis (AD) is associated with incident acne in adolescent and adults that is mostly mild, transient and treatable. There is a need for more knowledge about the risk and severity of acne in patients with AD. Objectives To examine the prevalence, incidence and risk of acne in adolescents and adults with AD using nationwide prescription data. Methods A matched cohort study of 6600 adults with AD and 66 000 controls was conducted using routinely and prospectively collected nationwide administrative data. Adjusted hazard ratios (HR) are reported with 95% confidence intervals (CIs). Results The 12‐month prevalence of acne was 3.7% in the general population and 3.9% among AD patients. The incidence rate of acne was highest among 12‐ to 18‐year‐old AD patients, and overall slightly higher in women with AD compared with males. The overall risk in patients with AD was similar with that of the general population (HR 0.96; 95% CI 0.88–1.06), whereas the risk of being treated for severe acne was reduced in AD patients (HR 0.59; 95% CI 0.47–0.73) and mainly among adolescents and young adults. The HR of acne increased with age reaching 1.41 (95% CI 1.07–1.87) for ages 30–39 years, and 2.07 (95% CI 1.42–3.03) for patients ≥40 years compared with controls. Conclusions The risk and severity of acne in AD patients change with age and sex, which may be used for the risk assessment of acne following treatment with Janus kinase 1 inhibitors.

BackgroundRapid skin improvement is a key treatment goal of patients with moderate‐to‐severe psoriasis (PsO).ObjectivesTo compare the speed of clinical improvement of approved biologics on the symptoms and signs of psoriasis assessed by patients using the validated Psoriasis Symptoms and Signs Diary (PSSD) through 12 weeks.MethodsPsoriasis Study of Health Outcomes (PSoHO) is an international, prospective, non‐interventional study that compares the effectiveness of anti‐interleukin (IL)‐17A biologics versus other biologics, together with pairwise comparisons of ixekizumab versus five individual biologics in patients with PsO. Using the PSSD 7‐day recall period, patients assessed the symptoms (itch, skin tightness, burning, stinging and pain) and signs (dryness, cracking, scaling, shedding/flaking, redness and bleeding) of their psoriasis (0–10). Symptom and sign summary scores (0–100) are derived from the average of individual scores. Percentage change in summary scores and proportion of patients with clinically meaningful improvements (CMI) in PSSD summary and individual scores are evaluated weekly. Longitudinal PSSD data are reported as observed with treatment comparisons analysed using mixed model for repeated measures (MMRM) and generalized linear mixed models (GLMM).ResultsAcross cohorts and treatments, eligible patients (n = 1654) had comparable baseline PSSD scores. From Week 1, the anti‐IL‐17A cohort achieved significantly larger score improvements in PSSD summary scores and a higher proportion of patients showed CMIs compared to the other biologics cohort through 12 weeks. Lower PSSD scores were associated with a greater proportion of patients reporting their psoriasis as no longer impacting their quality‐of‐life (DLQI 0,1) and a high level of clinical response (PASI100). Results also indicate a relationship between an early CMI in PSSD score at Week 2 and PASI100 score at Week 12.ConclusionsTreatment with anti‐IL‐17A biologics, particularly ixekizumab, resulted in rapid and sustained patient‐reported improvements in psoriasis symptoms and signs compared with other biologics in a real‐world setting.

Vitiligo-like depigmentation (VLD) is an immune-related adverse event (irAE) of checkpoint-inhibitor (CPI) treatment, which has previously been associated with a favourable outcome. The aim of this study was to explore clinical, biological and prognostic features of melanoma patients with VLD under CPI-treatment and to explore whether they exhibit a characteristic immune response profile in peripheral blood. Melanoma patients developing VLD under CPI were included in a prospective observational single-center cohort study. We collected and analysed clinical parameters, photographs and serum from 28 VLD patients. They received pembrolizumab (36%), nivolumab (11%), ipilimumab/nivolumab (32%) or clinical trial medications (21%). We performed a high-throughput proteomics assay (Olink), in which we identified a distinct proteomic signature in VLD patients in comparison to non-VLD CPI patients. Our clinical assessments revealed that VLD lesions had a predominantly symmetrical distribution pattern, with mostly smaller “freckle-like” macules and a preferential distribution in UV-exposed areas. Patients with previous targeted therapy showed a significantly longer time lapse between CPI initiation and VLD onset compared to non-pre-treated patients (12.5 vs. 6.25 months). Therapy responders exhibited a distinct proteomic profile when compared with non-responders in VLD such as upregulation of EDAR and downregulation of LAG3. ITGA11 was elevated in the VLD-group when compared to non-VLD-CPI-treated melanoma patients. Our findings demonstrate that on a proteomic level, VLD is characterized by a distinct immune signature when compared to CPI-treated patients without VLD and that therapy responsiveness is reflected by a characteristic immune profile. The pathomechanisms underlying these findings and how they could relate to the antitumoral response in melanoma remain to be elucidated.