Immunogenicity and skin clearance recapture in clinical studies of brodalumab.

Abstract

Antidrug antibodies (ADAs) may change pharmacokinetic or pharmacodynamic profiles of biologic therapies, potentially decreasing efficacy. To evaluate the potential effects of brodalumab immunogenicity on safety, efficacy, and retreatment. Data from 1 phase 2 and 3 phase 3 studies of brodalumab in psoriasis were analyzed. Overall, 2.7% of patients had positive test results for binding ADAs after receiving brodalumab; ADAs were transient in 1.4% of patients, and there were no neutralizing ADAs. Among ADA-positive patients, 60.0% (3/5) achieved a static physician's global assessment score of 0 or 1 at week 12 in the group receiving the brodalumab 210 mg every 2 weeks, compared with 79.1% (1131/1429) of ADA-negative patients. All patients (100%) who experienced return of disease and were retreated with brodalumab 210 mg every 2 weeks (none were ADA positive) achieved at least a 75% improvement in Psoriasis Area And Severity Index, ≥90% of whom regained response by week 8 of retreatment. Hypersensitivity reactions were less frequent with brodalumab than with placebo. Injection site reactions occurred in 1.8% of patients treated with brodalumab versus 2% of patients treated with ustekinumab. Retreatment could be assessed in only 1 phase 3 brodalumab study. Brodalumab compares favorably with other biologics in terms of immunogenicity and high rates of efficacy recapture upon retreatment.