Efficacy of brodalumab in ustekinumab-naive and -experienced patients with moderate-to-severe plaque psoriasis
Presenters: Hsu S1, Green L2, Keegan BR3, Kircik L4, Rastogi S5, Pillai R6, Israel RJ5
Affiliations: 1Temple University School of Medicine, Philadelphia, PA; 2George Washington University School of Medicine, Washington, DC; 3Psoriasis Treatment Center of Central New Jersey/Windsor Dermatology, East Windsor, NJ; 4Icahn School of Medicine at Mount Sinai, New York, NY; 5Valeant Pharmaceuticals North America LLC, Bridgewater, NJ; 6Dow Pharmaceutical Sciences, Petaluma, CA
Background/Objective: Brodalumab is a fully human anti–interleukin-17 receptor A (IL-17RA) monoclonal antibody that has shown efficacy in patients with moderate-to-severe plaque psoriasis. We evaluated the efficacy of brodalumab in a post-hoc analysis of a subset of patients with prior exposure to ustekinumab, a human anti-IL-12 and -IL-23 monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis who were enrolled in a Phase III, multicenter, randomized, double-blind, placebo-controlled study (AMAGINE-1).
Methods: During the induction phase, patients received brodalumab 210mg weekly for the first three weeks and every two weeks (Q2W) thereafter for 12 weeks. After 12 weeks, patients who achieved a static physician’s global assessment (sPGA) score of 0 or 1 continued to the withdrawal phase and were rerandomized 1:1 to receive brodalumab 210mg Q2W or placebo for up to 52 weeks. Beginning at Week 16, all rerandomized patients who experienced return of disease (sPGA ?3) qualified for retreatment with their induction dose of brodalumab 210mg and were imputed as nonresponders at the time of qualification. Skin clearance was monitored by the Psoriasis Area and Severity Index (PASI) and the sPGA.
Results: Of 167 patients who were randomized to brodalumab 210mg in the induction phase and continued into the withdrawal phase, 19.2 percent had taken ustekinumab prior to the start of the trial (n=32). Among patients receiving continuous brodalumab 210mg, rates of 100-percent reduction in PASI score (PASI 100) were 65.2 percent (n=43/66) and 76.5 percent (n=13/17) in ustekinumab-naive and -experienced patients, respectively (rates for placebo were 0 [n=0/69] and 0 [n=0/15], respectively). Similarly, rates of PASI 75 and PASI 90 were 84.8 percent (n=56/66) and 75.8 percent (n=50/66), respectively, in ustekinumab-naive patients and 94.1 percent (n=16/17) and 88.2 percent (n=15/17), respectively, in ustekinumab-experienced patients (rates for placebo were 0 [n=0 of 69] and 0 [n=0 of 69], respectively, in ustekinumab-naive patients and 0 [n=0/15] and 0 [n=0/15], respectively, in ustekinumab-experienced patients).
Conclusion: Brodalumab 210mg was associated with improved skin clearance efficacy in both patients with and without prior ustekinumab exposure.
Funding: This study was sponsored by Amgen Inc.