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

Abstract

Background Brodalumab is a monoclonal antibody that blocks multiple interleukin (IL)-17 family cytokines by binding to the shared A subunit of the IL-17 receptor. In Phase 3 trials, brodalumab provided high levels of skin clearance through 52 weeks in patients with moderate-to-severe psoriasis and was generally well tolerated.Objectives To assess efficacy response rates and safety outcomes through 120 weeks for patients with moderate-tosevere psoriasis who received brodalumab.Methods Safety and efficacy data were pooled for patients from AMAGINE-2 and À3 who received continuous brodalumab 210 mg every 2 weeks, or brodalumab 210 mg every 2 weeks after receiving either brodalumab 140 mg or placebo through Week 12. Efficacy data are presented using observed data, non-responder imputation (NRI) and a combination of NRI and missing at random assumption to account for missing data. Absolute PASI scores are presented using mixed-effect model repeated measure modelling and multiple imputation. ResultsBased on observed data at Week 120, 86% of the continuous brodalumab 210 mg group achieved PASI 90 and 74% achieved PASI 100. At Week 12, 58% of this group achieved absolute PASI ≤1; this proportion increased to approximately 80% at Week 52 and persisted through Week 120. Among patients receiving continuous brodalumab 210 mg, median duration of brodalumab exposure was 747 days and the overall exposure-adjusted event rate of treatment emergent adverse events per 100 patient-years was 329. Safety through 120 weeks was comparable to the results of the primary AMAGINE-2 and À3 studies. Patients who switched to brodalumab 210 mg after receiving either brodalumab 140 mg or placebo through Week 12 showed similar skin clearance and safety profiles. Conclusions Brodalumab treatment was well tolerated and resulted in high levels of skin clearance that were rapidly achieved and maintained through Week 120, supporting its long-term efficacy and safety profile.

Formulary Management of Biologics in Plaque Psoriasis

“…Not considered� The real-world impact of this assumption is unclear although there is direct comparative clinical trial evidence available that demonstrates new-generation biologics have improved efficacy compared to old-generation biologics. [42][43][44][45][46][47][48] Treatment switch No treatment switch was assumed during the analytical time frame� This was considered a simplification of the analysis. It remains unclear how treatment switch may impact the cost analysis as it would depend on what subsequent biological treatment patients would receive�…”

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 …”

Brodalumab for Plaque Psoriasis: A Canadian Real-World Experience at 2-Years Post-Launch

“…16,17 Brodalumab was found to have superior efficacy, long-term safety and was well-tolerated by patients. [17][18][19] Notably, complete skin clearance rates (defined as PASI 100) at week 12 were significantly higher with brodalumab than with ustekinumab (primary endpoint AMAGINE-2, 44% vs. 22%; AMAGINE-3, 37% vs. 19%; P < .001). 17 With the limitation inherent in the design of clinical trials, evidence from the patient experience in a real-world setting is valuable to completely assess therapies, especially for chronic diseases requiring long-term treatment.…”

“…16,17 Brodalumab was found to have superior efficacy, long-term safety and was well-tolerated by patients. 17 -19 Notably, complete skin clearance rates (defined as PASI 100) at week 12 were significantly higher with brodalumab than with ustekinumab (primary endpoint AMAGINE-2, 44% vs. 22%; AMAGINE-3, 37% vs. 19%; P < .001). 17…”