Recapture Rate of Brodalumab in Patients With a Lapse in Treatment

April 2020 | Volume 19 | Issue 4 | Original Article | 384 | Copyright © April 2020

Published online March 6, 2020

Mark Lebwohl MD,a Jennifer Cather MD,b April Armstrong MD MPH,c Abby Van Voorhees MD,d Abby Jacobson PA-Ce

aDepartment of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY bModern Research Associates, Dallas, TX cDepartment of Dermatology, University of Southern California, Los Angeles, CA dDepartment of Dermatology, Eastern Virginia Medical School, Norfolk, VA eOrtho Dermatologics (a division of Bausch Health US, LLC), Bridgewater, NJ

Abstract
The National Psoriasis Foundation has emphasized the importance of achieving skin clearance targets throughout the course of treatment. However, patients with psoriasis often stop and restart treatment for reasons such as psychological distress, dissatisfaction with treatment, inconvenience, cost, or comorbidities. Brodalumab is a fully human anti–interleukin-17 receptor A monoclonal antibody efficacious for the treatment of moderate-to-severe plaque psoriasis. This review discusses the efficacy and safety of brodalumab and other biologic therapies in patients with psoriasis who stop and restart treatment. These clinically relevant and important findings can help inform real-world treatment decisions.

J Drugs Dermatol. 2020;19(4): doi:10.36849/JDD.2020.5026

INTRODUCTION

In recent years, The National Psoriasis Foundation has emphasized the importance of achieving skin clearance targets during the course of treatment.1 However, many patients with psoriasis stop and restart treatment because of factors including psychological distress, dissatisfaction with treatment, inconvenience, cost, insurance barriers, comorbidities, and use of therapy only during flares when control is necessary.2-4 Multiple studies evaluating adherence to psoriasis medications found that 29%-88% of patients were classified as adherent, indicating that up to 71% of patients may stop their medication at some point during treatment.3 Moreover, many factors including comorbidities and likelihood of adherence influence the selection of psoriasis therapies.4-6 Inability to achieve sustained skin clearance extends to patients who withdraw from treatment and are subsequently retreated with the same or a different agent. Brodalumab is a fully human anti–interleukin-17 (IL-17) receptor A monoclonal antibody efficacious for the treatment of moderate-to-severe plaque psoriasis and is approved for moderate-to-severe psoriasis in adults who have experienced treatment failure or loss of response while receiving other systemic therapies.7 Studies have shown that messenger RNA levels and protein levels of IL-17A, IL-17C, and IL-17F are highly upregulated in psoriatic skin, with IL-17C and IL-17F having higher expression than that of IL-17A.8,9

Brodalumab has a unique mechanism of action among biologics for psoriasis by antagonizing IL-17 receptor A, resulting in the inhibition of multiple cytokines, such as IL-17A, IL-17C, and IL-17F,10-13 whereas secukinumab14 and ixekizumab15,16 neutralize only IL-17A. Understanding the efficacy and safety of brodalumab in patients who stop and restart treatment is important to inform clinical treatment decisions based on real-world circumstances.

Efficacy of Brodalumab in Patients Who Underwent Withdrawal and Retreatment With Brodalumab
The efficacy and safety of brodalumab have been established in three large phase 3 trials: AMAGINE-1, AMAGINE-2, and AMAGINE-3.17,18 The study design of AMAGINE-1 had a planned withdrawal phase in which patients who achieved a static physician’s global assessment score of 0 or 1 were eligible to be switched from brodalumab 210 mg every 2 weeks (Q2W) to placebo at week 12.18,19 At week 16, these patients were eligible for retreatment upon return of disease (defined as static physician's global assessment score ≥3; Figure 1). Reinitiation with brodalumab after treatment withdrawal led to recapture of week-12 skin clearance response within 16 weeks of reinitiation.20 Among patients who switched from brodalumab 210 mg Q2W to placebo at week 12, 94.0% (n=79) experienced return of disease at or after week 16 through week 52. Among patients in AMAGINE-1 who experienced return of disease and