Efficacy and safety of brodalumab in palmoplantar pustulosis: A 68-week randomized Phase 3 trial.

内容摘要

The efficacy and safety of brodalumab in Japanese patients with palmoplantar pustulosis (PPP) were demonstrated during the 16-week double-blind phase of a randomized controlled trial. However, long-term data are unavailable. To assess the efficacy and safety of brodalumab 210 mg administered subcutaneously (SC) repeatedly until Week 68 in PPP patients with moderate or severe pustules/vesicles in an open-label extension study. In a multicentre, Phase 3, randomized, double-blind, placebo-controlled trial, Japanese adults having a diagnosis of PPP for ≥24 weeks, PPP Area Severity Index (PPPASI) of ≥12, PPPASI subscore of pustules/vesicles of ≥2 and inadequate response to therapy were included. Patients completing the double-blind phase with brodalumab 210 mg or placebo (1:1) SC once every 2 weeks (Q2W) for 16 weeks were invited to enter the open-label extension to receive brodalumab for the subsequent 52 weeks. By Week 68, 35 patients in the brodalumab group and 43 patients in the placebo-to-brodalumab group completed the study, with discontinuations (28 and 20 patients, respectively) primarily due to patient withdrawal. At Week 68, the mean ± SD improvement of the PPPASI total score from baseline was 23.83 ± 12.28 and 22.37 ± 13.09 in the brodalumab and placebo-to-brodalumab groups, respectively. Continued improvement or trend for improvement was seen in the secondary endpoints such as PPPASI 50/75/90 responses and Dermatology Life Quality Index. The incidence of adverse events was 849.3/100 person-years. Otitis externa had the highest incidence (44.0/100 person-years; Grade 1 or 2 only). Infection-related events were frequent but controllable. Brodalumab SC 210 mg Q2W administered for 68 weeks showed a long-term benefit to both dermatological and quality of life indices in these patients. It is expected to be used in appropriate patients, considering both safety risks and efficacy benefits. Palmoplantar pustulosis (PPP) is a difficult‐to‐treat, chronic skin disease. In PPP, pustules and vesicles keep reappearing on palms and/or soles. In 2011, ~0.01% to 0.05% of people in Western countries and 0.12% in Japan had PPP. It is more common in women, the elderly and smokers. We conducted a long‐term trial in Japan to treat PPP with brodalumab. Brodalumab is a human monoclonal antibody that works against IL‐17RA. We analysed the benefit and safety of brodalumab in PPP. In the first 16 weeks, 126 patients participated. Patients received brodalumab (210 mg dose every 2 weeks) or a placebo. Both groups had similar baseline characteristics. In total, 112 patients completed the 16‐week period. Results for the 16‐week period are published previously. Patients from both groups willing to continue were treated with brodalumab. Some patients dropped out due to various reasons. In total, 78 of 126 patients completed the 68‐week study. Of these, 35 were from the brodalumab‐only and 43 from the placebo‐to‐brodalumab group. At Week 68, mean improvement from baseline of 23.83 and 22.37, respectively, was seen in the PPPASI disease score. The proportion of patients showing 50%, 75% or 90% reduction in disease severity increased from Week 16 to Week 68. Dermatology Life Quality Index also showed continuous improvement. Some adverse events occurred. However, there were no deaths. Infection‐related events were frequent but generally controllable. We observed continuous improvement in the brodalumab‐only group. Also, we observed ‘catch‐up’ improvement in the placebo‐to‐brodalumab group. Overall skin scores and quality of life scores improved. Our results support long‐term benefit with brodalumab in PPP treatment.