Dupilumab, a fully human IgG4 monoclonal antibody targeting the interleukin-4 receptor alpha (IL4Rα), substantially improves disease severity in patients with atopic dermatitis (AD). While recent daily practice studies have shown that dose reduction of dupilumab is possible in patients with controlled AD, the associated biological effects are currently unknown. Therefore, we studied the dupilumab levels in serum and effects of dupilumab on IL4Rα occupancy, T-cell functions and cytokine production within skin-homing (total CLA+ and CLA+/CCR4+) subpopulations in patients with AD who were treated with 300mg dupilumab subcutaneously every 2 weeks (Q2W), every 4 weeks (Q4W) and every 6 weeks (Q6W). As the time between injections increased, the dupilumab levels in serum and the amount of bound dupilumab (anti-IgG4) decreased. During treatment with 300mg dupilumab Q2W and Q4W, the IL4Rα was completely occupied regardless of the number of days between the injection of dupilumab and blood draw. Simultaneously, the Eczema Area and Severity Index (EASI) score remained stably low and IgE levels declined. During treatment with 300mg dupilumab Q6W, however, the IL4Rα became available again and the percentage of proliferating (Ki67+) and Th2 cytokine producing skin-homing CD4+ T-cells increased compared to dupilumab Q4W. This was also reflected in the clinical parameters with a slightly rising EASI score. In summary, 300mg dupilumab Q2W and Q4W stably inhibited IL4Rα with similar immunological and clinical effects. The biological tipping point for patients with AD who are treated with dupilumab seems to occur at the transition from 300mg dupilumab Q4W to 300mg dupilumab Q6W.

Dupilumab, a fully human IgG4 monoclonal antibody targeting the interleukin-4 receptor alpha (IL4Rα), substantially improves disease severity in patients with atopic dermatitis (AD). While recent daily practice studies have shown that dose reduction of dupilumab is possible in patients with controlled AD, the associated biological effects are currently unknown. Therefore, we studied the dupilumab levels in serum and effects of dupilumab on IL4Rα occupancy, T-cell functions and cytokine production within skin-homing (total CLA+ and CLA+/CCR4+) subpopulations in patients with AD who were treated with 300mg dupilumab subcutaneously every 2 weeks (Q2W), every 4 weeks (Q4W) and every 6 weeks (Q6W). As the time between injections increased, the dupilumab levels in serum and the amount of bound dupilumab (anti-IgG4) decreased. During treatment with 300mg dupilumab Q2W and Q4W, the IL4Rα was completely occupied regardless of the number of days between the injection of dupilumab and blood draw. Simultaneously, the Eczema Area and Severity Index (EASI) score remained stably low and IgE levels declined. During treatment with 300mg dupilumab Q6W, however, the IL4Rα became available again in a subset of patients and the percentage of proliferating (Ki67+) and Th2 cytokine producing skin-homing CD4+ T-cells increased compared to dupilumab Q4W. This was also reflected in the clinical parameters with a slightly rising EASI score. In summary, 300mg dupilumab Q2W and Q4W stably inhibited IL4Rα with similar immunological and clinical effects. The transition from 300mg dupilumab Q4W to 300mg dupilumab Q6W seems to be an important biological tipping point for disease control.

ESDR025 - Immunological changes in atopic dermatitis patients treated with different dosing intervals of dupilumab

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.