1. Brodalumab was more effective than either placebo or ustekinumab at reducing the severity of psoriasis after 12 weeks of treatment.
2. Consistent dosing of brodalumab helps to extend the treatment response to 1 year.
3. Treatment with brodalumab was associated with alterations in the immune system and greater frequency of certain infections, though in general the risk of infection was not different from that of ustekinumab.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Psoriasis is an inflammatory skin disease characterized by red, scaly and itchy plaques. Studies have shown that interleukin-17, a molecule involved in immune system signaling, plays a role in promoting psoriasis. Brodalumab is an antibody which targets a component of the interleukin-17 receptor and inhibits interleukin-17 signaling. Preliminary studies have shown that brodalumab can reverse psoriasis through its anti-interleukin-17 effect.
The AMAGINE-2 and 3 trials were two identically designed trials conducted at nearly 300 different centers around the world. The trials compared brodalumab against ustekinumab, another antibody-based treatment for psoriasis, and placebo. Both trials produced broadly similar results and showed that brodalumab at a dose of 210mg every 2 weeks was superior to both ustekinumab and placebo in reducing the severity of psoriasis symptoms at 12 weeks. The trials also showed that brodalumab therapy had to be sustained in order to maintain the treatment response.
The safety profile of brodalumab did not differ significantly from that of ustekinumab. The rates of serious infection were approximately 1 per 100 pts/yr of treatment with either brodalumab or ustekinumab.
In-Depth [randomized controlled trial]: The AMAGINE-2 and 3 trials were identically-designed randomized, double-blind, placebo-controlled phase 3 trials. Each trial enrolled nearly 1900 participants aged 18-75 with moderate-to-severe plaque psoriasis for at least 6 months and with involvement of at least 10% of the body-surface area. Severity of psoriasis was evaluated with the psoriasis area and severity index (PASI) and the static physician’s global assessment (sPGA) score. Patients were randomized to receive placebo, ustekinumab, lower-dose brodalumab (140 mg every 2 weeks) or higher-dose brodalumab (210mg every 2 weeks) for 12 weeks.
Brodalumab at either the higher or lower dose was significantly superior compared to the placebo for attainment of a 75% or greater reduction in PASI score (AMAGINE-2: 86% and 67% vs. 8%, p<0.001; AMAGINE-3: 85% and 69% vs. 6%, p<0.001). Brodalumab at either dose was superior to placebo for attainment of an sPGA score of 0 or 1 (clear or almost clear skin). Brodalumab at either dose was also superior to ustekinumab for attainment of a 100% reduction in baseline PASI score (AMAGINE-2 44% and 26% vs. 22%, p<0.001; AMAGINE-3: 37% and 27% vs. 19%, p<0.001).
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