Safety of Brodalumab in Plaque Psoriasis: Integrated Pooled Data from Five Clinical Trials

Abstract

Brodalumab is approved for treatment of moderate-to-severe plaque psoriasis. Here, we assess the safety profile of brodalumab using pooled safety data from five Phase II/III trials of brodalumab 140 mg or 210 mg. In total, 4,464 patients received brodalumab, representing 8,891.6 patient-years of exposure. During the placebo-controlled 12-week induction period, rates of serious adverse events per 100 patient-years were 10.8 and 9.6 (brodalumab 140 mg and 210 mg, respectively) versus 4.3 and 6.5 (ustekinumab and placebo, respectively); infections were the most frequent serious adverse event. Rates of serious adverse events during the comparator-controlled 52-week period were 14.4, 10.2 and 8.3 per 100 patient-years for brodalumab 210 mg, brodalumab 140 mg, and ustekinumab, respectively. Brodalumab was not associated with increased risks of malignancy, major adverse cardiac events, suicidal ideation and behaviour, or fatal events. Overall, brodalumab demonstrated an acceptable safety profile in short- and long-term treatment.

Long‐term efficacy and safety of brodalumab in moderate‐to‐severe plaque psoriasis: a post hoc pooled analysis of AMAGINE‐2 and ‐3

“…patient-years) and MACE (0.2 per 100 patient-years), were low and similar to rates in a pooled analysis of five brodalumab trials 13 ; rates of serious infections and MACE were similar to those observed with secukinumab. 14 Rates of Candida infections were relatively low (4.5 per 100 patient-years in the 210 mg Constant group), but slightly higher than those observed with secukinumab (1.3 per 100 patient-years).…”

“…As expected, using imputation methods to account for missing data showed a lower percentage of responders compared to observed data; at Week 120, 49% of the 210 mg Constant group maintained PASI 90 and 40% maintained PASI 100 using the NRI/MAR imputation method. Rates of AEs of special interest in the 210 mg Constant group, including serious infections (1.5 per 100 patient‐years), Crohn’s disease (0.2 per 100 patient‐years) and MACE (0.2 per 100 patient‐years), were low and similar to rates in a pooled analysis of five brodalumab trials 13 ; rates of serious infections and MACE were similar to those observed with secukinumab 14 . Rates of Candida infections were relatively low (4.5 per 100 patient‐years in the 210 mg Constant group), but slightly higher than those observed with secukinumab (1.3 per 100 patient‐years) 14 .…”

Revisiting the interleukin 17 family of cytokines in psoriasis: pathogenesis and potential targets for innovative therapies

“…As expected, this strategy is highly effective ( 70 ). The brodalumab clinical development program was abruptly interrupted for safety reasons (several cases of major adverse cardiovascular events in the brodalumab arm but not the placebo arm in one clinical study, resulting in a statistically significant safety signal) and subsequently resumed (brodalumab’s safety profile with regard to such major adverse cardiovascular events has recently been documented by an integrated safety analysis based on 5 clinical trials ( 71 ). Discontinuation of brodalumab treatment resulted in numerous relapses and even rebounds ( 72 ).…”

English version of Japanese guidance for use of biologics for psoriasis (the 2022 version)

“…In the References section, the following are listed as sources for efficacy and safety data in pivotal studies of each biologic in and outside of Japan and for the results of the Japanese postmarketing surveillance of each biologic: infliximab, 9-18 adalimumab, [19][20][21][22][23][24][25] ustekinumab, [26][27][28][29][30][31][32][33][34] secukinumab, [35][36][37][38][39][40][41][42][43][44][45] ixekizumab, [46][47][48][49][50][51] brodalumab, [52][53][54][55][56][57][58][59][60] guselkumab, [61][62][63][64][65][66][67]…”

“…Table 1 shows the list of biologics available for psoriasis in Japan. In the References section, the following are listed as sources for efficacy and safety data in pivotal studies of each biologic in and outside of Japan and for the results of the Japanese post‐marketing surveillance of each biologic: infliximab, 9–18 adalimumab, 19–25 ustekinumab, 26–34 secukinumab, 35–45 ixekizumab, 46–51 brodalumab, 52–60 guselkumab, 61–68 risankuzumab, 69–72 certolizumab pegol, 73–77 tildorakizumab, 78–83 bimekizumab, 84–88 infliximab BS, 89,90 adalimumab BS 91 …”