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Background Guselkumab has demonstrated favourable safety and efficacy across individual clinical studies in adults with moderate-to-severe plaque psoriasis. Objectives To evaluate the safety of guselkumab in patients with psoriasis using pooled data from seven phase II/III studies (X-PLORE, VOYAGE 1, VOYAGE 2, NAVIGATE, ORION, ECLIPSE, Japan registration). Methods All studies, except NAVIGATE and ECLIPSE (active comparator-controlled only), included a 16-week placebo-controlled period; X-PLORE, VOYAGE 1 and VOYAGE 2 included both placebo and active controls. In most studies, guselkumab-treated patients received 100-mg subcutaneous injections at week 0, week 4, and then every 8 weeks thereafter. Safety data were summarized for the placebo-controlled period (weeks 0–16) and through the end of the reporting period (up to 5 years). Incidence rates of key safety events were integrated post hoc, adjusted for the duration of follow-up and reported per 100 patient-years (PY). Results During the placebo-controlled period, 544 patients received placebo (165 PY) and 1220 received guselkumab (378 PY). Through the end of the reporting period, 2891 guselkumab-treated patients contributed 8662 PY of follow-up. During the placebo-controlled period, in the guselkumab and placebo groups, respectively, rates of adverse events (AEs) were 346/100 PY and 341/100 PY, and infections were 95.9/100 PY and 83.6/100 PY. Rates of serious AEs (6.3/100 PY vs. 6.7/100 PY), AEs leading to discontinuation (5.0/100 PY vs. 9.7/100 PY), serious infections (1.1/100 PY vs. 1.2/100 PY), malignancy (0.5 patients/100 PY vs. 0.0 patients/100 PY) and major adverse cardiovascular events (MACE; 0.3/100 PY vs. 0.0/100 PY) were low and comparable between guselkumab and placebo. Through the end of the reporting period, safety event rates were lower than or comparable to the placebo-controlled period in guselkumab-treated patients: AEs, 169/100 PY; infections, 65.9/100 PY; serious AEs, 5.3/100 PY; AEs leading to discontinuation, 1.6/100 PY; serious infections, 0.9/100 PY; malignancy, 0.7/100 PY; and MACE, 0.3/100 PY. There were no cases of Crohn disease, ulcerative colitis, opportunistic infection or active tuberculosis related to guselkumab. Conclusions In this comprehensive analysis of 2891 guselkumab-treated patients with psoriasis followed for up to 5 years (8662 PY), guselkumab demonstrated favourable safety, consistent with previous reports. Safety event rates in guselkumab-treated patients were similar to those observed with placebo and were consistent throughout long-term treatment. [ABSTRACT FROM AUTHOR]

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]