A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis

作者：Papp, K. A.^*; Reich, K.; Paul, C.; Blauvelt, A.; Baran, W.; Bolduc, C.; Toth, D.; Langley, R. G.; Cather, J.; Gottlieb, A. B.; Thaci, D.; Krueger, J. G.; Russell, C. B.; Milmont, C. E.; Li, J.; Klekotka, P. A.; Kricorian, G.; Nirula, A.

来源：British Journal of Dermatology, 2016, 175(2): 273-286.

DOI：10.1111/bjd.14493

• SYMPTOM INVENTORY
• IMMUNE-SYSTEM
• CELLS
• PATHOGENESIS

Background The interleukin-17 cytokine family plays a central role in psoriasis pathogenesis. @@@ Objectives To evaluate the efficacy and safety of brodalumab, a human anti-interleukin-17 receptor antibody, in treating patients with moderate-to-severe plaque psoriasis. @@@ Methods In this phase III, double-blind, placebo-controlled study (NCT01708590; AMAGINE-1), adult patients in the U.S.A., Canada and Europe were randomized to brodalumab (140 or 210 mg) or placebo every 2 weeks (Q2W), with an additional dose at week 1, for a 12-week induction phase. At week 12, patients receiving brodalumab who achieved static Physician's Global Assessment 0 or 1 (sPGA success) were rerandomized to the placebo or induction dose. After week 16, patients with sPGA >= 3 were re-treated with the induction dose. After >= 12 weeks of retreatment, patients with sPGA 2 for >= 4 weeks or sPGA >= 3 were rescued with brodalumab 210 mg Q2W. At week 12, patients randomized to brodalumab with sPGA >= 2 or placebo received brodalumab 210 mg Q2W. Coprimary end points were the percentage of patients with >= 75% improvement in Psoriasis Area and Severity Index score (PASI 75) and sPGA success at week 12. @@@ Results There were 661 patients randomized: 220 placebo, 219 brodalumab 140 mg and 222 brodalumab 210 mg. At week 12, 60% (140 mg) and 83% (210 mg) vs. 3% (placebo) achieved PASI 75, and 54% (140 mg) and 76% (210 mg) vs. 1% (placebo) achieved sPGA success. The safety profile was considered acceptable. @@@ Conclusions Brodalumab therapy resulted in significant clinical benefit and an acceptable safety profile in patients with moderate-to-severe plaque psoriasis.

• 出版日期2016-8