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.

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.

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.

Biosimilars are increasingly being licensed as equipotent drugs, although efficacy and safety data are not available for all clinical indications. Accordingly, the efficacy of the biosimilar filgrastim Zarzio® combined with vinorelbine for chemo-mobilization of CD34+ hematopoietic progenitor cells (HPC) in patients with multiple myeloma has not been evaluated yet. We compared the efficacy of vinorelbine combined with this biosimilar filgrastim for HPC mobilization to vinorelbine plus original filgrastim (Neupogen®). Overall, 105 multiple myeloma patients received vinorelbine 35 mg/m intravenously on day 1 and either original filgrastim (n = 61;58%) or biosimilar filgrastim (n = 44;42%) at a dose of 5 µg per kg body weight (BW) twice daily subcutaneously starting day 4 until the end of the collection procedure. Leukapheresis was scheduled to start on day 8 and performed for a maximum of three consecutive days until at least 4 × 10 HPC/kg BW were collected. All patients proceeded to leukapheresis. In 102 (97%) patients the leukapheresis sessions were started as planned at day 8. The median number of collected HPC was 7.3 × 10 /kg BW (0.2-18.3) with original filgrastim compared to 9 × 10 /kg BW (4.2-23.8) with the biosimilar filgrastim (P = 0.16). HPC collection was successful in 57 (93%) of 61 patients of the original group and in all 44 (100%) patients of the biosimilar group (P = 0.14). No differences were observed regarding side effects. Duration of neutrophil engraftment after autologous HPC transplantation was similar between the two groups (P = 0.17). Biosimilar and original filgrastim achieve comparable results in combination with vinorelbine regarding HPC mobilization and transplantation outcome in multiple myeloma patients. J. Clin. Apheresis 32:21-26, 2017. © 2016 Wiley Periodicals, Inc.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itch, dry skin and recurrent eczematous lesions. 1 Food allergy (FA) is triggered by exposure to a food antigen, and can manifest as urticaria, angioedema, gastrointestinal symptoms, respiratory problems and anaphylaxis. 2 In patients with co-occurring AD, eczema may worsen in hours to days after food exposure, while reduced exposure, or complete exclusion of food allergens in infancy, may improve or completely prevent AD. [3][4][5] It was traditionally assumed that primary sensitization to food allergens mainly occur as a result of allergen exposure in the gut, but it is now recognized that food sensitization (FS) can develop following primary allergen exposure on the skin. [6][7][8] Individuals with FS and FA often have skin-barrier impairment, even without co-occurring AD, 9-11 but AD seems to increase risk of developing FS and FA in a severity dependent manner due to significant skin-barrier impairment. [12][13][14][15][16][17][18][19] The skin may be impaired due to multiple factors such as reduction in chain length of essential lipids including ceramides, but also due to reductions of crucial skin barrier

Background Prolonged systemic antibiotic treatment is often a part of management of hidradenitis suppurativa (HS). Although biologic therapies are now available, the patient's treatment journey leading to biologic therapy is unclear. Objectives To examine treatment patterns and duration of systemic treatment use in patients with HS preceding biologic therapy. Methods We identified all patients with HS receiving treatment with biologics in the Danish National Patient Registry from 2010 to 2018 and extracted their entire prescription history of specific systemic treatments from the Danish National Prescription Registry since its inception in 1995. The patients' treatment journeys are graphically displayed through Sankey diagrams and box plots generated to show temporal distributions. Descriptive patient characteristics were presented as frequencies with percentages for categorical variables and as means with SDs or medians with interquartile ranges (IQRs) for continuous variables. Results A total of 225 patients with HS were included. Patients had most frequently been treated with penicillin (n = 214; 95Á1%), dicloxacillin (n = 194; 86Á2%), tetracycline (n = 145; 64Á4%) and rifampicin/clindamycin (n = 111; 49Á3%), as well as the retinoids isotretinoin and acitretin, and dapsone. Prior to biologic therapy, patients received a mean of 4Á0 (SD 1Á3) different systemic therapies, across a mean of 16Á9 (SD 11Á3) different treatment series. The mean time from first systemic therapy until biologic therapy was initiated was 15Á3 (SD 5Á1) years [8Á2 (SD 5Á9) years when excluding penicillin and dicloxacillin]. Conclusions Patients with HS who receive biologic therapy have long preceding treatment histories with multiple drug classes and treatment series, many of which are supported by relatively weak evidence in HS. Delay in the initiation of biologic therapy may represent a missed opportunity to prevent disease progression.What is already known about this topic?• The treatment journey leading to biologic therapy in patients with HS has not previously been investigated.

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