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Background: Data from early-stage studies suggested that interleukin (IL)-4 and IL-13 are requisite drivers of atopic dermatitis, evidenced by marked improvement after treatment with dupilumab, a fully-human monoclonal antibody that blocks both pathways. We aimed to assess the efficacy and safety of several dose regimens of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments.Methods: In this randomised, placebo-controlled, double-blind study, we enrolled patients aged 18 years or older who had an Eczema Area and Severity Index (EASI) score of 12 or higher at screening (≥16 at baseline) and inadequate response to topical treatments from 91 study centres, including hospitals, clinics, and academic institutions, in Canada, Czech Republic, Germany, Hungary, Japan, Poland, and the USA. Patients were randomly assigned (1:1:1:1:1:1), stratified by severity (moderate or severe, as assessed by Investigator's Global Assessment) and region (Japan vs rest of world) to receive subcutaneous dupilumab: 300 mg once a week, 300 mg every 2 weeks, 200 mg every 2 weeks, 300 mg every 4 weeks, 100 mg every 4 weeks, or placebo once a week for 16 weeks. We used a central randomisation scheme, provided by an interactive voice response system. Drug kits were coded, providing masking to treatment assignment, and allocation was concealed. Patients on treatment every 2 weeks and every 4 weeks received volume-matched placebo every week when dupilumab was not given to ensure double blinding. The primary outcome was efficacy of dupilumab dose regimens based on EASI score least-squares mean percentage change (SE) from baseline to week 16. Analyses included all randomly assigned patients who received one or more doses of study drug. This trial is registered with ClinicalTrials.gov, number NCT01859988.Findings: Between May 15, 2013, and Jan 27, 2014, 452 patients were assessed for eligibility, and 380 patients were randomly assigned. 379 patients received one or more doses of study drug (300 mg once a week [n=63], 300 mg every 2 weeks [n=64], 200 mg every 2 weeks [n=61], 300 mg every 4 weeks [n=65], 100 mg every 4 weeks [n=65]; placebo [n=61]). EASI score improvements favoured all dupilumab regimens versus placebo (p<0·0001): 300 mg once a week (-74% [SE 5·16]), 300 mg every 2 weeks (-68% [5·12]), 200 mg every 2 weeks (-65% [5·19]), 300 mg every 4 weeks (-64% [4·94]), 100 mg every 4 weeks (-45% [4·99]); placebo (-18% [5·20]). 258 (81%) of 318 patients given dupilumab and 49 (80%) of 61 patients given placebo reported treatment-emergent adverse events; nasopharyngitis was the most frequent (28% and 26%, respectively).Interpretation: Dupilumab improved clinical responses in adults with moderate-to-severe atopic dermatitis in a dose-dependent manner, without significant safety concerns. Our findings show that IL-4 and IL-13 are key drivers of atopic dermatitis.Funding: Sanofi and Regeneron Pharmaceuticals. INSET: Panel: Research in context.. [ABSTRACT FROM AUTHOR]

Background: ESPRIT is an ongoing, 10-year, observational registry, evaluating long-term safety and effectiveness of adalimumab treatment in routine clinical practice for patients with moderate to severe, chronic plaque psoriasis., Objectives: Initial 5-year results are reported., Methods: Two populations were analyzed: the "all-treated" population received 1 or more adalimumab doses in registry, continuing adalimumab treatment from a current prescription or previous study participation, and included the "new-prescription" population initiating adalimumab 4 weeks or earlier preregistry entry., Results: Data were collected from September 26, 2008, through November 30, 2013, for all-treated (n = 6059), which included new-prescription (n = 2580, 42.6%); median registry exposure was 765 and 677 days, respectively. In all-treated, rate (events per 100 patient-years of total adalimumab exposure [E/100PY]) of serious treatment-emergent adverse events (inside or outside of the registry) was 4.3 E/100PY, serious infection 1.0 E/100PY, malignancies 0.9 E/100PY (nonmelanoma skin cancers 0.6 E/100PY; melanomas <0.1 E/100PY). Standardized mortality ratio was 0.30 (95% confidence interval 0.19-0.44). Physician Global Assessment clear or minimal (effectiveness parameter) was achieved by 57.0% at 12 months and 64.7% at 60 months of treatment., Limitations: Observational data are subject to outcome-reporting bias., Conclusion: No new safety signals were observed with adalimumab treatment during this initial 5-year registry review. Observed number of deaths was below expected. As-observed effectiveness remained stable through 60 months., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Prompt identification and treatment of psoriatic arthritis (PsA) in patients with psoriasis is critical to reducing the risk of joint damage, disability, and comorbidities., Objective: We sought to estimate PsA prevalence in patients with plaque psoriasis in 34 dermatology centers in 7 European and North American countries., Methods: Consecutive patients were evaluated by dermatologists for plaque psoriasis and subsequently by rheumatologists for PsA. PsA prevalence was estimated primarily based on rheumatologists' assessment of medical history, physical examination, and laboratory tests., Results: Of 949 patients evaluated, 285 (30%) had PsA (95% confidence interval 27-33) based on rheumatologists' assessment. PsA diagnosis changed in 1.2% of patients when diagnostic laboratory tests were added to medical history and physical examination. Of 285 patients given the diagnosis of PsA, 117 (41%) had not been previously given the diagnosis., Limitations: Bias may have been introduced by lack of standardized diagnostic criteria and unbalanced recruitment based on country populations., Conclusions: In this study, almost a third of patients with psoriasis seen in dermatology centers had PsA as determined by rheumatologists. More than a third of patients with PsA had not been previously given the diagnosis. Clinical evaluation alone is often sufficient basis for PsA diagnosis, but laboratory test results may be helpful in some patients., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

About 20% of all psoriasis patients require photo- and/or systemic therapy because of the severity of their disease. Side effects, contraindications, insufficient clinical responses, and lack of long-term efficacy underline the need for novel and improved anti-psoriatic therapies. In recent years, the technology has been established to generate therapeutic molecules from living cells capable of inhibiting disease-relevant mediators or cell-cell interactions. Several of these so-called biologics interfering with key steps in the immunopathogenesis of psoriasis have the potential to meet this need with regard to treating moderate to severe psoriasis. Here, the Psoriasis Study Group of the Arbeitsgemeinschaft Dermatologische Forschung (ADF) analyses the established anti-psoriatic treatment modalities. With the shortcomings of these options in mind, biologics with an immediate relevance for clinical application in the treatment of psoriasis are discussed. The focus is on their potential medical advantages along with safety aspects. Moreover, legal and economical aspects with an impact on the use of biologics are addressed.