Efficacy of Dupilumab in Different Racial Subgroups of Adults With Moderate-to-Severe Atopic Dermatitis in Three Randomized, Placebo-Controlled Phase 3 Trials
August 2019 | Volume 18 | Issue 8 | Original Article | 804 | Copyright © August 2019
Andrew F. Alexis MD MPH,a Marta Rendon MD,B Jonathan I. Silverberg MD,c David M. Pariser MD,D Benjamin Lockshin MD,e Christopher E.M. Griffiths MD,f Jamie Weisman MD,g Andreas Wollenberg MD,h Zhen Chen PhD,i John D. Davis PhD,i Meng Li PhD,j Laurent Eckert PhD,k Abhijit Gadkari PhD,i Brad Shumel MD,i Ana B. Rossi MD,l Neil M.H. Graham MD,i Marius Ardeleanu MDi
ªDepartment of Dermatology, Mount Sinai West, New York, NY
BRendon Center for Dermatology and Aesthetic Medicine, Boca Raton, FL
cDepartment of Dermatology, Preventive Medicine and Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL
DDepartment of Dermatology, Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA
EU.S. Dermatology Partners, Rockville, MD
fDermatology Centre NIHR Manchester Biomedical Research Centre, University of Manchester, Manchester, UK
gAdvanced Medical Research, PC, Atlanta, GA
hDepartment of Dermatology and Allergy, Ludwig Maximilian University, Munich, Germany
IRegeneron Pharmaceuticals, Inc., Tarrytown, NY
jSanofi, Bridgewater, NJ
kSanofi, Chilly-Mazarin, France
lSanofi Genzyme, Cambridge, MA
Abstract
Dupilumab, a monoclonal antibody that blocks the shared receptor subunit for interleukin (IL)-4 and IL-13, is currently approved for the treatment of adults with inadequately controlled moderate-to-severe atopic dermatitis (AD). The efficacy and safety of dupilumab for AD among racial subgroups is unknown. This post hoc analysis from three phase 3 trials assessed the efficacy and safety of dupilumab vs placebo by racial subgroup (White, Asian, Black/African American). Data from LIBERTY AD SOLO 1 (NCT02277743), SOLO 2 (NCT02277769), and CHRONOS (NCT02260986) were pooled. Outcomes included mean and percent change from baseline to week 16 in the key therapeutic domains Eczema Area and Severity Index (EASI), Peak Pruritus Numerical Rating Scale (NRS), Dermatology Life Quality Index (DLQI), and Patient-Oriented Eczema Measure, as well as Investigator’s Global Assessment and pain or discomfort assessed by the European Quality of Life-5 Dimensions 3 level questionnaire. A total of 2,058 patients (White n=1,429, Asian n=501, Black/African American n=128) were included in the current analysis. Baseline demographics and disease characteristics were balanced between treatment groups and racial subgroups. In the three trials, dupilumab significantly (P<0.0001) improved all assessed outcomes compared with placebo in the White and Asian subgroups. In the smaller Black/African American subgroup, dupilumab significantly (P<0.0001) improved EASI endpoints and mean changes in Peak Pruritus NRS and DLQI vs placebo, with positive numeric trends favoring dupilumab in all other endpoints. Dupilumab was generally well tolerated, with an acceptable safety profile in all racial subgroups. Serious adverse events occurred more frequently with placebo; treatment discontinuations due to adverse events were rare in all treatment groups. Significant clinical improvement and a favorable benefit-risk profile can be achieved with dupilumab treatment in patients of White, Asian, and Black/African American racial subgroups with moderate-to-severe AD inadequately controlled with topical medications.
ClinicalTrials.gov identifiers: NCT02277743, NCT02277769, NCT02260986
J Drugs Dermatol. 2019;18(8):804-813.
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INTRODUCTION
Atopic dermatitis (AD) is a clinically defined, chronic skin condition characterized by intense itch, disruption of the skin barrier, and upregulation of type 2 immune responses.1-3 The disease has an adverse impact on quality of life (QoL) and is associated with sleep loss, anxiety, and depression.4,5 Considerable heterogeneity in AD characteristics and disease course has been noted between racial groups and region.6,7 Genetic variations that influence AD incidence,
