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
In all treatment groups within each racial subset, 44-73% of patients reported ≥1 TEAE (Table 2). TE-SAEs and discontinuation of study drug generally occurred more often in patients receiving placebo (Table 2). One death was reported in a 31-year-old White male receiving dupilumab 300 mg qw in SOLO 2, but was not considered to be treatment related.21 Conjunctivitis was the only common TEAE of clinical concern attributable to dupilumab (Table 2).
In all three trials and among all racial and treatment groups, dupilumab PK steady state was achieved by week 16 (Figure 3). The mean trough concentrations were comparable between White and Asian patients, with slightly lower levels noted in Black/African American patients.
Dupilumab with or without concomitant TCS significantly improved AD signs, symptoms, and QoL across all racial subgroups studied in this analysis, with efficacy generally consistent with the data reported for the overall populations in SOLO 1 and 221 and CHRONOS.22
Although the original trial publications also presented categorical efficacy endpoints,21,22 this analysis focuses on continuous outcomes, which are the most sensitive and best suited for subset analyses, particularly with relatively small patient subsets. The reported endpoints in the present analysis provide a comprehensive racial subgroup analysis by assessing all major domains that define AD severity and response to treatment, including objective signs, subjective symptoms, and QoL.
Efficacy outcomes in White and Asian patients were similar to those in the overall populations of the trial.21,22 While numeric trends always favored dupilumab vs placebo in the Black/African American subset, statistical significance in efficacy outcomes was not achieved consistently in either dupilumab group due primarily to the low numbers of Black/African American patients. Various other factors, including biologic, may have played a role in the observed inconsistencies between Black/African American patients and White and Asian patients.
Slightly lower mean trough concentrations were noted in Black/ African American patients compared with White and Asian patients, which could be due, at least in part, to the higher average body weight of Black/African American patients in this analysis. Body weight was assessed as a potential confounding factor of this analysis, but weight-adjusted and weight-unadjusted