Immunogenicity and Skin Clearance Recapture in Clinical Studies of Brodalumab
BACKGROUND Antidrug antibodies (ADA) may change pharmacokinetic or pharmacodynamic profiles of biologic therapies, potentially decreasing efficacy.
OBJECTIVE To evaluate potential effects of brodalumab immunogenicity on safety, efficacy, and retreatment.
METHODS Data from one phase 2 and three phase 3 studies of brodalumab in psoriasis were analyzed.
RESULTS Overall, 2.7% of patients tested positive for binding ADA after receiving brodalumab; ADA were transient in 1.4% of patients, and there were no neutralizing ADA. Among ADA-positive patients, 60.0% (3/5) achieved static physician's global assessment score of 0 or 1 at week 12 in the brodalumab 210 mg every 2 weeks (Q2W) group, compared with 79.1% (1131/1429) of ADA-negative patients. Among all patients who experienced return of disease and were retreated with brodalumab 210 mg Q2W (none were ADA positive), 100% achieved psoriasis area and severity index 75% improvement, ≥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 brodalumab-treated patients vs 2% of ustekinumab-treated patients.
LIMITATIONS Retreatment could only be assessed in one phase 3 brodalumab study.
CONCLUSION Brodalumab compares favorably with other biologics in terms of immunogenicity and high rates of efficacy recapture upon retreatment.