Treating moderate to severe atopic dermatitis with dupilumab resulted in significant improvements in signs, symptoms, and quality of life, with a favorable safety profile across racial subgroups, according to a study published in the Journal of Drugs in Dermatology.
The aim of this post hoc analysis was to evaluate the efficacy, safety, and pharmacokinetics of dupilumab in the treatment of moderate to severe atopic dermatitis among different racial subgroups. This analysis included the three randomized, placebo-controlled, phase 3 clinical trials LIBERTY AD SOLO 1, SOLO 2, and CHRONOS. All three trials randomly assigned patients into a cohort receiving a 300-mg dose of subcutaneous dupilumab once a week, a cohort receiving 300 mg of subcutaneous dupilumab once every 2 weeks, or a cohort receiving placebo. Racial subgroups self-identified as white, Asian, and black. Efficacy was assessed at 16 weeks measuring changes in Eczema Area and Severity Index, Peak Pruritus Numerical Rating Scale, Dermatology Life Quality Index, Patient-Oriented Eczema Measure, Investigator’s Global Assessment, and the European Quality of Life-5 Dimensions 3 level questionnaire. All treatment-emergent adverse events, treatment-emergent serious adverse event, treatment discontinuations, and incidents of conjunctivitis were monitored for safety outcomes. Pharmacokinetic profiles were assessed using dupilumab serum levels.
Of the patients pooled into this study, 1429 were white, 501 were Asian, and 128 were black. Overall, baseline demographics, measurements, and characteristics were similar among all three subgroups, with a high disease burden and a median atopic dermatitis duration of >20 years. The white and Asian subgroups in either dupilumab cohort reported significant improvements in Eczema Area and Severity Index, Investigator’s Global Assessment, Patient-Oriented Eczema Measure, Peak Pruritus Numerical Rating Scale, European Quality of Life-5 Dimensions 3 level questionnaire, and Dermatology Life Quality Index over the placebo cohort at week 16 (P <.0001, for all). The subgroups of participants who were black in either dupilumab cohort reported significant improvements in the Eczema Area and Severity Index score, Peak Pruritus Numerical Rating Scale, and Dermatology Life Quality Index over the placebo cohort. The subgroup of black participants in the once a week 300 mg of dupilumab cohort also reported significant improvements in the Patient-Oriented Eczema Measure and the Investigator’s Global Assessment over the placebo cohort.
Overall treatment with dupilumab had an acceptable safety profile, with treatment-emergent adverse events comparable across all cohorts. Conjunctivitis and injection-site reactions did occur more frequently in the dupilumab cohorts but they were mild to moderate in nature. Conjunctivitis was the only clinical adverse event of concern related to the use of dupilumab. Patients receiving placebo experienced more atopic dermatitis exacerbations, skin infections, and medication discontinuation than patients receiving dupilumab.
With regard to pharmacokinetics, all subgroups in the dupilumab cohorts reached steady-state levels of dupilumab by week 16. Mean trough concentrations were similar in the cohorts of white and Asian participants but slightly lower in the subgroup of black participants.
Limitations of this study include the short-term analysis of only 16 weeks, not analyzing the differences in doses among the dupilumab cohorts, and the small sample size in the subgroup of black participants, potentially leading to the low level of significance.
The researchers concluded, “[i]rrespective of racial subgroup, dupilumab results in significant clinical improvement and a favorable benefit-risk profile in patients with moderate-to-severe [atopic dermatitis] inadequately controlled with topical medications.”
Disclosure: This clinical trial was supported by Sanofi and Regeneron Pharmaceuticals, Inc. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Alexis AF, Rendon M, Silverberg JI, et al. Efficacy of dupilumab in different racial subgroups of adults with moderate-to-severe atopic dermatitis in three randomized, placebo-controlled phase 3 trials. J Drugs Dermatol. 2019;18(8):804-813.