BACKGROUND: In this phase 2, randomized, double-blind, placebo-controlled, dose-ranging study, we assessed the efficacy and safety of brodalumab (AMG 827), a human anti-interleukin-17-receptor monoclonal antibody, for the treatment of moderate-to-severe plaque psoriasis. METHODS: We randomly assigned patients with a score of 12 or higher on the psoriasis area-and-severity index (PASI, on which scores range from 0 to 72, with higher scores indicating more severe disease) and with 10% or more of their body-surface area affected by psoriasis to receivebrodalumab (70 mg, 140 mg, or 210 mg at day 1 and weeks 1, 2, 4, 6, 8, and 10 or 280 mg monthly) or placebo. The primary end point was the percentage improvement from baseline in the PASI score at week 12. Secondary end points included improvement of at least 75% and at least 90% in the PASI score and the score on the static physician's global assessment at week 12. RESULTS: A total of 198 patients underwent randomization. At week 12, the mean percentage improvements in the PASI score were 45.0% among patients receiving 70 mg of brodalumab, 85.9% among those receiving 140 mg, 86.3% among those receiving 210 mg, 76.0% among those receiving 280 mg, and 16.0% among those receiving placebo (P<0.001 for all comparisons with placebo). An improvement of at least 75% and at least 90% in the PASI score at week 12 was seen in 77% and 72%, respectively, of the patients in the 140-mg brodalumab group and in 82% and 75%, respectively, of the patients in the 210-mg group, as compared with 0% in the placebo group (P<0.001 for all comparisons). The percentage of patients with a static physician's global assessment of clear or minimal disease was 26%, 85%, 80%, and 69% with the 70-mg, 140-mg, 210-mg, and 280-mg doses, respectively, of brodalumab, as compared with 3% with placebo (P<0.01 for all comparisons with placebo). Two cases of grade 3 neutropenia were reported in the 210-mg brodalumab group. The most commonly reported adverse events in the combined brodalumab groups were nasopharyngitis (8%), upper respiratory tract infection (8%), and injection-site erythema (6%). CONCLUSIONS:Brodalumab significantly improved plaque psoriasis in this 12-week, phase 2 study. (Funded by Amgen; ClinicalTrials.gov number, NCT00975637.).
RCT Entities:
BACKGROUND: In this phase 2, randomized, double-blind, placebo-controlled, dose-ranging study, we assessed the efficacy and safety of brodalumab (AMG 827), a human anti-interleukin-17-receptor monoclonal antibody, for the treatment of moderate-to-severe plaque psoriasis. METHODS: We randomly assigned patients with a score of 12 or higher on the psoriasis area-and-severity index (PASI, on which scores range from 0 to 72, with higher scores indicating more severe disease) and with 10% or more of their body-surface area affected by psoriasis to receive brodalumab (70 mg, 140 mg, or 210 mg at day 1 and weeks 1, 2, 4, 6, 8, and 10 or 280 mg monthly) or placebo. The primary end point was the percentage improvement from baseline in the PASI score at week 12. Secondary end points included improvement of at least 75% and at least 90% in the PASI score and the score on the static physician's global assessment at week 12. RESULTS: A total of 198 patients underwent randomization. At week 12, the mean percentage improvements in the PASI score were 45.0% among patients receiving 70 mg of brodalumab, 85.9% among those receiving 140 mg, 86.3% among those receiving 210 mg, 76.0% among those receiving 280 mg, and 16.0% among those receiving placebo (P<0.001 for all comparisons with placebo). An improvement of at least 75% and at least 90% in the PASI score at week 12 was seen in 77% and 72%, respectively, of the patients in the 140-mg brodalumab group and in 82% and 75%, respectively, of the patients in the 210-mg group, as compared with 0% in the placebo group (P<0.001 for all comparisons). The percentage of patients with a static physician's global assessment of clear or minimal disease was 26%, 85%, 80%, and 69% with the 70-mg, 140-mg, 210-mg, and 280-mg doses, respectively, of brodalumab, as compared with 3% with placebo (P<0.01 for all comparisons with placebo). Two cases of grade 3 neutropenia were reported in the 210-mg brodalumab group. The most commonly reported adverse events in the combined brodalumab groups were nasopharyngitis (8%), upper respiratory tract infection (8%), and injection-site erythema (6%). CONCLUSIONS:Brodalumab significantly improved plaque psoriasis in this 12-week, phase 2 study. (Funded by Amgen; ClinicalTrials.gov number, NCT00975637.).
Authors: Seemal R Desai; Ilona J Frieden; Joel M Gelfand; Whitney High; Arthur Kavanaugh; Ashfaq A Marghoob; David M Ozog; Ted Rosen; Linda Stein Gold; Bruce Strober; Neil Swanson; George Martin Journal: J Clin Aesthet Dermatol Date: 2015-09