Long-term efficacy and safety of brodalumab in psoriasis through 120 weeks and after withdrawal and retreatment: subgroup analysis of a randomized phase III trial (AMAGINE-1)

Abstract

Summary Background Brodalumab is efficacious for the treatment of moderate‐to‐severe plaque psoriasis through 52 weeks. Objectives To evaluate the efficacy and safety of brodalumab through 120 weeks, including following withdrawal and retreatment. Methods At baseline, patients were randomized to brodalumab (n = 222) or placebo (n = 220). At week 12, patients achieving a static Physician's Global Assessment (sPGA) score of 0 or 1 (sPGA 0/1) with brodalumab were rerandomized to brodalumab (n = 83) or placebo (n = 84; later re‐treated with brodalumab if sPGA ≥ 3 occurred), and patients receiving placebo switched to brodalumab (n = 208). Safety was assessed by exposure‐adjusted rates of treatment‐emergent adverse events. Results Among those who achieved sPGA 0/1 at week 12 and were rerandomized to brodalumab, 96% and 80% using observed data, respectively, and 74% and 61% using nonresponder imputation, respectively, achieved 75% improvement in Psoriasis Area and Severity Index (PASI 75) and PASI 100 at week 120. Following withdrawal from brodalumab, return of disease occurred after a mean ± SD duration of 74·7 ± 50·5 days. Among those who switched from brodalumab to placebo at week 12, PASI 75 rates using observed data and nonresponder imputation were 55% and 51% at week 20, respectively and 94% and 75% at week 120, respectively; PASI 100 rates at week 120 were 75% and 60%, respectively. Efficacy was maintained through week 120 in those receiving brodalumab after placebo. No new safety signals were observed. Conclusions These findings indicate that brodalumab is efficacious and safe for continuous long‐term treatment of psoriasis, and support the potential for response after discontinuation and retreatment.

Two-Year US Pharmacovigilance Report on Brodalumab

“…Additionally, the rate of arthralgia in the 1-year report was similar to that presented here (0.07 and 0.04 per PY, respectively) [7]. Finally, in a long-term analysis of the AMAGINE-1 trial, rates of arthralgia improved from 11.6% in year 1 to 4.1% in year 3 [5].…”

“…Arthralgia was the most common AE listed in the package insert for patients receiving brodalumab for 12 weeks in clinical trials (n = 71; 4.7%) [1]. It was also among the most frequently reported AEs in long-term analyses of AMAGINE-1 (n = 100; 7.5 events per 100 PY) [5] and AMAGINE-2 (n = 295; 9.1 events per 100 PY) [6] and in the 1-year pharmacovigilance analysis (n = 16; 0.07 events per PY) [7]. In this 2-year analysis, there were 73 reports of arthralgia (0.04 events per PY; Table 1).…”

“…In long-term analyses of the AMAGINE-1 and AMAGINE-2 studies, arthralgia, headache, diarrhea, oropharyngeal pain, and Candida infections were among the most frequent adverse events (AEs) with brodalumab treatment over 120 weeks [5,6]. We previously reported 1-year US pharmacovigilance AE data of brodalumab [7].…”

New brodalumab psoriasis outcome data suggests that intermittent treatment is as effective as continuous dosing. Is it time to re‐evaluate our treatment regimens?

“…In the Papp et al . study reported in this edition of the BJD , 1 a low prevalence of ADA in their patients, suggesting low immunogenicity, may explain the good rates of recapture of response after a period of treatment withdrawal. Low prevalence of ADA associated with biological therapies targeting the IL‐17 pathway (including secukinumab, ixekizumab and brodalumab), has been reported previously 8 .…”

“…In this issue of the BJD , Papp et al . report a randomized placebo‐controlled trial of the long‐term efficacy of brodalumab through 120 weeks including a successful demonstration of an intermittent treatment regimen 1 …”