Summary Background A T‐helper (Th) cell subset Th17 preferentially produces interleukin (IL)‐17 and plays a pivotal role in the pathogenesis of psoriasis. However, the pathological roles of IL‐17 cascades in generalized pustular psoriasis (GPP) and psoriatic erythroderma (PsE) have not been well established. Objectives To evaluate the efficacy and safety of brodalumab, a human immunoglobulin G2 monoclonal antibody against human IL‐17‐receptor A (IL‐17RA), in Japanese patients with GPP and PsE. Methods This was an open‐label, multicentre, long‐term phase III study in Japanese patients with rare and severe types of psoriasis. Patients received brodalumab 140 mg at day 1 and weeks 1 and 2, and then every 2 weeks until week 52. The primary endpoint was the Clinical Global Impression of Improvement (CGI). Safety evaluations included treatment‐emergent adverse events (AEs) and changes in laboratory parameters. Results A total of 12 patients with GPP and 18 with PsE were enrolled. Ten patients with GPP and 16 with PsE completed the study. At week 52 (last observation carried forward), CGI remission or improvement was achieved in 11 patients with GPP and 18 with PsE. The most commonly reported AE was nasopharyngitis (33·3%). Five serious AEs occurred during the study. However, none was considered treatment‐related. Conclusions Brodalumab significantly improved the symptoms of patients with GPP and PsE throughout the 52 weeks, and demonstrated favourable safety profiles without any new safety signals. Inhibition of IL‐17RA‐mediated signalling by brodalumab is expected to be a promising new treatment option for patients with GPP and PsE.

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Brodalumab showed a sustained clinical response and an acceptable safety profile through 52 weeks in Japanese patients with moderate-to-severe plaque psoriasis in this open-label extension study.

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Brodalumab, an interleukin-17 receptor A inhibitor, demonstrated rapid and robust efficacy with a favorable safety profile in patients with moderate to severe plaque psoriasis. Here, we present data from a multicenter, open-label extension study in patients with plaque psoriasis with/without psoriatic arthritis who completed 64 weeks of treatment with brodalumab (140 or 210 mg, every 2 weeks [Q2W]). Patients were enrolled to evaluate the longterm safety and efficacy of a modified dose of brodalumab. Eligible patients were switched to a reduced dose of brodalumab (140 mg every 4 weeks on day 1) in the extension study; the dose and dosing interval were modified sequentially at the physician's discretion (minimum 140 mg every 8 weeks and maximum 210 mg Q2W) until drug approval, after which all patients were switched to 210 mg Q2W for postmarketing surveillance. Of the 129 patients enrolled, 107 (82.9%) completed the 108-week or more extension study. All patients had psoriasis that was well controlled with brodalumab treatment on day 1. Improvement in psoriasis-related symptoms, evaluated with the Psoriasis Area and Severity Index, Psoriasis Scalp Severity Index, Dermatology Life Quality Index, Nail Psoriasis Severity Index, and American College of Rheumatology 20, 50 and 70, was maintained during the 108week extension study. Brodalumab treatment was well tolerated throughout, and no new safety signals were identified. The most commonly reported treatment-related adverse event was nasopharyngitis, followed by influenza and oral candidiasis. No cases of serious candida infection or Crohn's disease were observed in this study. Serious treatment-related adverse events, such as appendicitis, brain abscess, bacterial meningitis, colon cancer, immunoglobulin A nephropathy and tubulointerstitial nephritis, were reported in one patient each. No anti-brodalumab-binding antibodies or brodalumab-neutralizing antibodies were detected in any patient throughout the extension study. Overall, the long-term efficacy and safety of brodalumab were demonstrated over 108 weeks.