The Safety and Efficacy of Roflumilast Cream 0.15% and 0.05% in Patients With Atopic Dermatitis: Randomized, Double-Blind, Phase 2 Proof of Concept Study
February 2023 | Volume 22 | Issue 2 | 139 | Copyright © February 2023
Published online January 27, 2023
Melinda J. Gooderham MS MDa, Leon H. Kircik MDb, Matthew Zirwas MDc, Mark Lee MDd, Steven E. Kempers MDe, Zoe D. Draelos MDf, Laura K. Ferris MD PhDg, Terry M. Jones MDh, Etienne Saint-Cyr Proulx MDi, Robert Bissonnette MDi, Neal Bhatia MDj, Robert A. Koppel MDk, Scott T. Guenthner MDlm, Kimmie Eads MSNm, Howard Welgus MDn, Charlotte Merritt MBAn, Meg Elias BSNn, Lynn Navale MSn, Robert C. Higham MSn, Michael Droege PhDn, David R. Berk MDn
aSKiN Centre for Dermatology, Probity Medical Research and Queen’s University, Peterborough, Ontario, Canada;
bIcahn School of Medicine at Mount Sinai, New York, Indiana Medical Center, Indianapolis, IN, Physicians Skin Care, PLLC, Louisville, KY, and DermResearch, PLLC, Louisville, KY;
cDermatologists of the Central States, Probity Medical Research, and Ohio University, Bexley, OH;
dProgressive Clinical Research, San Antonio, TX ;
eMinnesota Clinical Study Center, Fridley, MN;
fDermatology Consulting Services, PLLC, High Point, NC ;
gUniversity of Pittsburgh Department of Dermatology, Pittsburgh, PA;
hUS Dermatology Partners, Bryan, TX;
iInnovaderm Research, Montreal, Quebec, Canada;
jTherapeutics Clinical Research, San Diego, CA;
kKoppel Dermatology, Metairie, LA;
lThe Dermatology Center of Indiana, PC, Plainfield, IN;
mThe Indiana Clinical Trials Center, PC, Plainfield, IN;
nArcutis Biotherapeutics, Inc., Westlake Village, CA
Abstract
Background: Patients with atopic dermatitis (AD) need safe and effective topical treatments.
Objective: To assess safety and efficacy of roflumilast cream in patients with mild to moderate AD.
Methods: In this phase 2, proof of concept trial, patients (N=136) aged ≥12 years with AD were randomized to once-daily roflumilast cream 0.15%, roflumilast cream 0.05%, or vehicle cream for 4 weeks. Absolute change from baseline in Eczema Area and Severity Index (EASI) score at week 4 (primary endpoint), percentage change and responder rates, Validated Investigator Global Assessment-AD (vIGA-AD), and safety were assessed.
Results: At week 4, mean absolute changes in EASI were -6.4 (P=0.097 vs vehicle), -6.0 (P=0.356), and -4.8 with roflumilast 0.15%, roflumilast 0.05%, and vehicle, respectively. Significant improvements were observed for percentage change from baseline in EASI, patients reaching 75% improvement in EASI, and patients achieving vIGA-AD score of "clear" or "almost clear." Treatment-related adverse events (AEs) occurred in 2 (2.2%) patients receiving roflumilast (mild rash and moderate application site pain). Only 1 (1.1%) patient receiving roflumilast discontinued study/drug due to an AE.
Limitations: Small number of patients.
Conclusions: Results support additional larger clinical trials of roflumilast cream to assess its potential as a once-daily, nonsteroidal topical AD treatment. ClinicalTrials.gov identifier NCT03916081
J Drugs Dermatol. 2023;22(2):139-147. doi:10.36849/JDD.7295
Citation: Gooderham MJ, Kircik LH, Zirwas M, et al. The safety and efficacy of roflumilast cream 0.15% and 0.05% in patients with atopic dermatitis: Randomized, double-blind, phase 2 proof of concept study. J Drugs Dermatol. 2023;22(2):139-147. doi:10.36849/JDD.7295
INTRODUCTION
Atopic dermatitis (AD) is a common chronic inflammatory skin disease affecting children and adults. Most patients with mild to moderate AD are treated with topical anti-inflammatory therapy - corticosteroids or calcineurin inhibitors - in combination with emollients.1 However, side effects and poor adherence limit long-term use of topical corticosteroids, particularly on the face and other sensitive areas.1 Additionally, topical calcineurin inhibitors may cause stinging/burning, and the labeling contains a warning for development of rare cases of malignancies (eg, skin and lymphoma), although recent clinical data do not suggest higher risk compared with the general population.2
Phosphodiesterase 4 (PDE4) is the predominant 3',5'-cyclic adenosine monophosphate (cAMP)-degrading enzyme in inflammatory cells and has increased activity in AD.3,4 Inhibiting PDE4 directly attenuates inflammation by reducing breakdown of cAMP.5 Moreover, PDE4 inhibition, through its effect on cAMP, has an antipruritic effect that is early and distinct from its anti-inflammatory effect.6,7 Oral roflumilast, a PDE4 inhibitor, is approved to reduce risk of exacerbations
