Long‐term safety of brodalumab in Japanese patients with plaque psoriasis: An open‐label extension study

Abstract

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.

Relationship between serum trough levels and efficacy of brodalumab from a post hoc exploratory analysis of a Japanese study in patients with plaque psoriasis

“…This was a post hoc exploratory analysis of a multicenter, open‐label, long‐term extension study (NCT02052609) 18 in patients with plaque psoriasis (psoriasis vulgaris, psoriatic arthritis), which changed into a post‐marketing surveillance (PMS; NCT04183881; July 04 to December 31, 2016) 18 study following approval of brodalumab 210 mg every 2 weeks (Q2W) in Japan.…”

“…Patients with plaque psoriasis who transitioned from a Phase III study of brodalumab in Japan 13 were included in this analysis. Detailed patient criteria have been previously reported 18 …”

“…In the preceding Phase III study (Fig. 1), patients received subcutaneous brodalumab 140 mg every 4 weeks (Q4W) until the end of study (EOS; Day 1 of the current study) 18 . From Week 2 to Week 28, the dosage could be maintained at 140 mg Q4W or switched directly to 210 mg Q2W, the dose could be maintained and dosing interval shortened (140 mg Q4W → 140 mg Q2W), or dose could be escalated and dosing interval shortened in a stepwise manner (140 mg Q4W → 140 mg Q2W → 210 mg Q2W) at the physician’s discretion based on the static Physician’s Global Assessment (sPGA) score (≥3 or maintained at 2 [mild] for ≥4 weeks on a 6‐point scale: 0, clear/no apparent disease; to 5, severe disease) 10 .…”

“…Following Week 28 until the start of the PMS, besides dose escalations and changes in dosing frequency (140 mg Q2W/Q4W/every 8 weeks [Q8W] or 210 mg Q2W), stepwise dose reductions were also permitted at the physician’s discretion. All patients were switched to the approved brodalumab dose at the start of the PMS study 18 …”

“…To ensure accurate estimation of brodalumab trough levels, a missed dose beyond ± 7 days of the specified assessment day was included as a protocol deviation for this analysis, unlike for the safety analysis 18 . For any unscheduled change in dosage, data at the next visit were considered representative for the switching point.…”