INTRODUCTION
Psoriasis is driven by proinflammatory cytokines, including interleukin (IL) 17, IL-23, and tumor necrosis factor alpha (TNF-α), resulting in keratinocyte hyperproliferation.1 Several biologic therapies that treat moderate-to-severe psoriasis target TNF-α (etanercept, infliximab, adalimumab), IL-12/23 (ustekinumab), IL-17A (secukinumab, ixekizumab), and IL-23 (guselkumab, risankizumab).2 Unique among biologic therapies, brodalumab is a human IL-17 receptor A (IL-17RA) antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies.3 Although the efficacy of brodalumab has been established in clinical trials, monitoring of real-world data is necessary to characterize its effectiveness. The objective of this review is to summarize real-world evidence of brodalumab, including nonsponsored open-label and real-world studies, to enhance the understanding of its effectiveness. A graphical summary of this review is shown in Figure 1.
Brodalumab: Mechanism of Action
Brodalumab is a recombinant, fully human monoclonal antibody antagonist of human IL-17RA.3 Brodalumab has a distinct mechanism of action (MOA) that blocks IL-17 signaling, disrupting the inflammatory feedback loop between immune cells and keratinocytes that contributes to psoriasis pathology.4,5 In a biomarker analysis, by 12 weeks, brodalumab had significantly reduced the gene expression levels of multiple inflammatory proteins in psoriatic plaques compared with placebo (Figure 2).6 Additionally, unlike the IL-17A inhibitor ixekizumab, brodalumab normalized psoriasis-associated genes in human skin cells typically activated by IL-17A, IL-17C, and IL-17F.7 This downregulation of multiple inflammatory mediators demonstrates the broad effect of brodalumab on the immunopathology of psoriasis. The unique MOA of brodalumab may contribute to its rapid and sustained efficacy in phase 3 clinical trials (AMAGINE-1/-2/-3) and open-label extension studies,8-12 and in patients with prior biologic therapy failure.4,13
Brodalumab: Mechanism of Action
Brodalumab is a recombinant, fully human monoclonal antibody antagonist of human IL-17RA.3 Brodalumab has a distinct mechanism of action (MOA) that blocks IL-17 signaling, disrupting the inflammatory feedback loop between immune cells and keratinocytes that contributes to psoriasis pathology.4,5 In a biomarker analysis, by 12 weeks, brodalumab had significantly reduced the gene expression levels of multiple inflammatory proteins in psoriatic plaques compared with placebo (Figure 2).6 Additionally, unlike the IL-17A inhibitor ixekizumab, brodalumab normalized psoriasis-associated genes in human skin cells typically activated by IL-17A, IL-17C, and IL-17F.7 This downregulation of multiple inflammatory mediators demonstrates the broad effect of brodalumab on the immunopathology of psoriasis. The unique MOA of brodalumab may contribute to its rapid and sustained efficacy in phase 3 clinical trials (AMAGINE-1/-2/-3) and open-label extension studies,8-12 and in patients with prior biologic therapy failure.4,13
