INTRODUCTION
Long-term maintenance of clear skin is a primary treatment goal for most patients with psoriasis. Ineffective response or loss of response to systemic therapy necessitates a change in treatment. In a study of biologic treatment among patients with psoriasis, 23% of patients had a less than/equal to 90-day gap in therapy during a 12-month period; of those patients, 77% switched to an alternative biologic therapy.1 Notably, during the first year of biologic therapy, 13% of patients discontinue therapy because of ineffectiveness.2 Therefore, effective second-line therapies are needed.
Brodalumab is an interleukin-17 (IL-17) receptor A antagonist approved by the US Food and Drug Administration (FDA) for the systemic treatment of moderate-to-severe plaque psoriasis in adults who have failed to respond or lost response to other systemic therapies.3 Although multiple biologics targeting IL-17A are available for the systemic treatment of psoriasis, patients may lack or lose response to these treatments, potentially because of the overexpression of multiple IL-17 family members and functional redundancy among IL-17 cytokines.4 By targeting IL-17 receptor A, brodalumab inhibits signaling from multiple IL-17 family members, including IL-17A, IL-17C, and IL-17F.5 This mechanism of action is associated with high efficacy rates in psoriasis, including among patients who do not respond to anti–IL-17A biologics, and may also show promising efficacy in other inflammatory skin conditions.6-12 Treatment with brodalumab also improves health-related quality of life (HRQOL) and patient-reported measures of mental health comorbidities.13,14 Real-world evidence supports the favorable safety profile of brodalumab.8-11,15
This narrative review discusses the mechanism of action of brodalumab in inflammatory skin conditions, focusing on how it relates to clinical and real-world efficacy, response after previous biologic failure, and improvements in mental health and HRQOL. Thus, this review summarizes recent research studies that evaluate brodalumab, other biologic therapies for psoriasis, and patients with prior biologic exposure, as well as published data from brodalumab clinical studies.
Brodalumab Blocks Pivotal Mediators of Inflammatory Skin Disease
Psoriasis is a chronic, immune-mediated inflammatory skin disease driven by T-cell activation, overexpression of proinflammatory cytokines, and dysregulation of the IL-23/helper T cell 17 (TH17) inflammatory response.16-19 IL-23 plays a pivotal upstream role in the pathogenesis of psoriasis by activating TH17 cells to stimulate production of IL-17.16 The IL-17 family of cytokines plays an important role in host defense, inflammation, and
Brodalumab is an interleukin-17 (IL-17) receptor A antagonist approved by the US Food and Drug Administration (FDA) for the systemic treatment of moderate-to-severe plaque psoriasis in adults who have failed to respond or lost response to other systemic therapies.3 Although multiple biologics targeting IL-17A are available for the systemic treatment of psoriasis, patients may lack or lose response to these treatments, potentially because of the overexpression of multiple IL-17 family members and functional redundancy among IL-17 cytokines.4 By targeting IL-17 receptor A, brodalumab inhibits signaling from multiple IL-17 family members, including IL-17A, IL-17C, and IL-17F.5 This mechanism of action is associated with high efficacy rates in psoriasis, including among patients who do not respond to anti–IL-17A biologics, and may also show promising efficacy in other inflammatory skin conditions.6-12 Treatment with brodalumab also improves health-related quality of life (HRQOL) and patient-reported measures of mental health comorbidities.13,14 Real-world evidence supports the favorable safety profile of brodalumab.8-11,15
This narrative review discusses the mechanism of action of brodalumab in inflammatory skin conditions, focusing on how it relates to clinical and real-world efficacy, response after previous biologic failure, and improvements in mental health and HRQOL. Thus, this review summarizes recent research studies that evaluate brodalumab, other biologic therapies for psoriasis, and patients with prior biologic exposure, as well as published data from brodalumab clinical studies.
Brodalumab Blocks Pivotal Mediators of Inflammatory Skin Disease
Psoriasis is a chronic, immune-mediated inflammatory skin disease driven by T-cell activation, overexpression of proinflammatory cytokines, and dysregulation of the IL-23/helper T cell 17 (TH17) inflammatory response.16-19 IL-23 plays a pivotal upstream role in the pathogenesis of psoriasis by activating TH17 cells to stimulate production of IL-17.16 The IL-17 family of cytokines plays an important role in host defense, inflammation, and
