Study results published in the British Journal of Dermatology from a subanalysis of 3 clinical trials support the safety and efficacy of dupilumab for the treatment of atopic dermatitis in Japanese adults.
Investigators abstracted Japanese cohort data from 3 clinical trials of dupilumab: AD-1021 (NCT01859988), a 16-week phase 2b dose-finding trial (n=27); LIBERTY AD SOLO 1 (NCT02277743), a 16-week phase 3 placebo-controlled monotherapy trial (n=106); and LIBERTY AD CHRONOS (NCT02260986) , a 52-week phase 3 placebo-controlled study of dupilumab treatment in tandem with topical corticosteroids (n=117). Analyses were conducted on the Japanese enrollees in each trial; outcomes in the Japanese cohort were compared with those in the general study populations. Primary efficacy outcomes included: percentage of patients achieving ≥75% reduction on the Eczema Area and Severity Index (EASI-75), percentage of patients achieving a score of 0 or 1 on the Investigator’s Global Assessment (IGA), patient-rated quality of life, and reduction in Numerical Rating Scale (NRS) itch score. Treatment-emergent adverse events were monitored in Japanese patients receiving dupilumab. The investigators also assessed changes in serum concentrations of type 2 inflammation biomarkers, including thymus and activation-regulated chemokine (TARC) and immunoglobin E (IgE).
Baseline demographic and clinical characteristics were similar in both the Japanese cohort and the overall study population. However, baseline disease severity was higher in the Japanese cohort compared with the total study group; Japanese patients had a higher median EASI score and a higher median percentage of body surface area affected by atopic dermatitis. In all studies, dupilumab was associated with significant improvements in atopic dermatitis parameters, including pruritus and patient quality of life. In AD-1021, dupilumab was associated with a significantly greater percentage of patients achieving improvements of ≥ 3 points or ≥ 4 points in weekly average Peak Pruritus NRS. In both SOLO 1 and CHRONOS, a greater percentage of the dupilumab groups achieved EASI-75 or IGA scores of 0 or 1 compared with controls.
The magnitude of effect observed with dupilumab was comparable between Japanese patients and the general study cohort. The safety profile of dupilumab was similar between treatment groups; Japanese patients were not at increased risk for adverse events. Compared with placebo, dupilumab was associated with an increased incidence of injection site reactions and conjunctivitis. Dupilumab was also associated with rapid reductions in TARC levels and gradual reductions in IgE levels.
Dupilumab with and without topical corticosteroids was an effective and well tolerated treatment for atopic dermatitis in Japanese adults.
As study limitations, investigators noted the small study cohorts and the post hoc design of analyses. Of note, dupilumab was also associated with reductions in TARC and IgE, known biomarkers of inflammation. “Immunologic differences in atopic dermatitis pathology in Asian patients may be secondary to type 2 immune activation,” the investigators hypothesized.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures
Katoh N, Kataoka Y, Saeki H, et al. Efficacy and safety of dupilumab in Japanese adults with moderate-to-severe atopic dermatitis: a subanalysis of three clinical trials [published online September 28, 2019]. Br J Dermatol. doi:10.1111/bjd.18565