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

Abstract

SummaryBackground 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.

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

“…Treatment with secukinumab for psoriasis patients in a phase III trial shows that more than half of the patients accomplish almost complete remission after 12 weeks of treatment, as determined by the Psoriasis Area and Severity Index (PASI 90), and show better efficacy than a tumour necrosis factor inhibitor (etanercept) 11. Ixekizumab, another monoclonal antibody against IL‐17, and Brodalumab, a monoclonal antibody against IL‐17RA, are also effective for the treatment of psoriasis in phase III trials12, 13 and approved for the treatment of psoriasis. Secukinumab has also been approved for the treatment of ankylosing spondylitis 97…”

“…Interleukin‐17 is also implicated in various inflammatory/autoimmune disease models such as experimental autoimmune encephalomyelitis (EAE), arthritis in IL‐1 receptor antagonist‐deficient (Il1rn –/– ) mice and imiquimod‐induced psoriatic dermatitis in mice 6, 7, 8, 9, 10. Anti‐IL‐17 and anti‐IL‐17RA antibodies are effective to treat patients with psoriasis and psoriatic arthritis 11, 12, 13. Interleukin‐17 is also important for the maintenance of intestinal barrier integrity and its functional deficiency causes the development of inflammatory bowel diseases 14, 15, 16.…”

Psoriasis, Depression, and Inflammatory Overlap: A Review

“…Ustekinumab reduced the relative risk of depression by 55% as measured by the Hospital Anxiety and Depression Scale (HADS) [49]. In a phase III randomized controlled trial evaluating the efficacy of brodalumab in patients with psoriasis, HADS scores for both treatment groups (140 mg of brodalumab, n = 216; 210 mg of brodalumab, n = 221) were improved as compared with the placebo group (p \ 0.01) [50].…”

Keratinocyte-Derived IL-17E Contributes to Inflammation in Psoriasis

“…Blockade of IL-17RA ameliorates psoriasis clinical signs and symptoms at least as effectively as neutralization of IL-17A (Langley et al, 2014;Papp et al, 2016), suggesting that other IL-17 family members may play a clinical relevant role.…”