BACKGROUND: Early clinical studies suggested that the anti-interleukin-17 
receptor A monoclonal antibody brodalumab has efficacy in the treatment of 
psoriasis.
METHODS: In two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with 
moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 
mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight 
≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients 
receiving brodalumab were randomly assigned again to receive a brodalumab 
maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, 
or every 8 weeks; patients receiving ustekinumab continued to receive 
ustekinumab every 12 weeks, and patients receiving placebo received 210 mg of 
brodalumab every 2 weeks. The primary aims were to evaluate the superiority of 
brodalumab over placebo at week 12 with respect to at least a 75% reduction in 
the psoriasis area-and-severity index score (PASI 75) and a static physician's 
global assessment (sPGA) score of 0 or 1 (clear or almost clear skin), as well 
as the superiority of brodalumab over ustekinumab at week 12 with respect to a 
100% reduction in PASI score (PASI 100).
RESULTS: At week 12, the PASI 75 response rates were higher with brodalumab at 
the 210-mg and 140-mg doses than with placebo (86% and 67%, respectively, vs. 8% 
[AMAGINE-2] and 85% and 69%, respectively, vs. 6% [AMAGINE-3]; P<0.001); the 
rates of sPGA scores of 0 or 1 were also higher with brodalumab (P<0.001). The 
week 12 PASI 100 response rates were significantly higher with 210 mg of 
brodalumab than with ustekinumab (44% vs. 22% [AMAGINE-2] and 37% vs. 19% 
[AMAGINE-3], P<0.001). The PASI 100 response rates with 140 mg of brodalumab 
were 26% in AMAGINE-2 (P=0.08 for the comparison with ustekinumab) and 27% in 
AMAGINE-3 (P=0.007). Rates of neutropenia were higher with brodalumab and with 
ustekinumab than with placebo. Mild or moderate candida infections were more 
frequent with brodalumab than with ustekinumab or placebo. Through week 52, the 
rates of serious infectious episodes were 1.0 (AMAGINE-2) and 1.3 (AMAGINE-3) 
per 100 patient-years of exposure to brodalumab.
CONCLUSIONS: Brodalumab treatment resulted in significant clinical improvements 
in patients with moderate-to-severe psoriasis. (Funded by Amgen; AMAGINE-2 and 
AMAGINE-3 ClinicalTrials.gov numbers, NCT01708603 and NCT01708629.).