Error: 429: HTTP/2 429 More Than Skin Clearance: Connecting Brodalumab's Mechanism of Action to Patient Outcomes in Psoriasis - JDDonline - Journal of Drugs in Dermatology

More Than Skin Clearance: Connecting Brodalumab’s Mechanism of Action to Patient Outcomes in Psoriasis

December 2025 | Volume 24 | Issue 12 | 1231 | Copyright © December 2025


Published online November 25, 2025

John Koo MDa, George Han MD PhDb, Mark Lebwohl MDc, Abby Jacobson PA-Cd

aUniversity of California San Francisco Psoriasis and Skin Treatment Center, San Francisco, CA
bNYC Health + Hospitals/Elmhurst, Elmhurst, NY
cIcahn School of Medicine at Mount Sinai, New York, NY
dBausch Health Companies Inc, Bridgewater, NJ

Abstract
Psoriasis has profound negative impacts on quality of life (QOL), including stigmatization, discrimination, occupational challenges, and mental health concerns, which are correlated with disease severity. Effective, long-term symptom control can dramatically improve the psychological and social outcomes for patients with psoriasis, though certain mechanisms of action of biologic therapies may contribute to reduced or diminished efficacy, need for treatment switching, and reduced QOL. Brodalumab is the only approved biologic indicated for moderate-to-severe plaque psoriasis that binds to interleukin-17 (IL-17) receptor A rather than targets specific IL-17 cytokines, which may contribute to its high clinical efficacy among patients who have lost responses to other biologic therapies and may also lead to sustained improvements in QOL. In biologic-experienced and biologic-naive patients, brodalumab has demonstrated optimal efficacy and improvements in QOL in both clinical trials and real-world studies, including improvements over other biologic therapies. This has the potential to dramatically improve the mental and social burdens faced by patients with moderate-to-severe psoriasis.

 

INTRODUCTION

Moderate-to-severe psoriasis is associated with substantial burden, including increased depression and anxiety and reduced quality of life (QOL).1 Skin clearance with biologic therapies is associated with improved QOL; however, psoriatic disease may fail to respond to certain agents, leading to a lack of efficacy and disease recurrence and contributing to a frustrating cycle of treatment switching.2,3 Differences in the mechanism of action (MOA) of available therapies may result in various response rates and durability of responses, which lead to differential impact on QOL.3,4

Brodalumab is a fully human monoclonal antibody antagonist of the human interleukin-17 receptor A (IL-17RA) that is 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.5 Unlike other biologics that target specific IL-17 cytokines, brodalumab is the only approved biologic for psoriasis that binds IL-17RA, blocking signaling from multiple IL-17 family members, including IL-17A, IL-17C, IL-17E, IL-17F, and IL-17A/F.4 This comprehensive receptor-level blockade may contribute to brodalumab's clinical efficacy in patients after failed treatment with other targeted therapies, including IL-17 cytokine inhibitors, and may lead to improvements in QOL.6

This narrative review examines the humanistic burden of psoriasis, evaluating how complete and sustained skin clearance affects psychosocial outcomes and QOL, with a focus on brodalumab's unique MOA and its ability to improve dermatological and mental health outcomes, even in patients who have experienced prior biologic treatment failure. A graphical summary of this review is shown in Figure 1.

Patient Burden Associated With Psoriasis and Treatment Nonresponse
Disease Burden
Psoriasis has a profound negative impact on patients, from stigmatization to occupational challenges and mental health concerns.7 A survey of 514 patients with psoriasis showed that perceived stigmatization was experienced by 73% of patients.8 Stigmatization was associated with higher impact on daily life; lower education; higher disease visibility, severity, and duration; and higher levels of social inhibition.8

Additionally, psoriasis is associated with poor mental health outcomes, including depression, anxiety, suicidality, obsessive-compulsive behavior, somatization, and interpersonal sensitivity.1,9,10 Rates of depression can reach 34% among patients with psoriasis10 and are higher in men than women experiencing severe psoriasis and in younger vs older patients

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