Association of Serum Dupilumab Levels at 16 Weeks with Treatment Response and Adverse Effects in Patients with Atopic Dermatitis: A Prospective Clinical Cohort Study from the BioDay Registry

Abstract

Importance: The registered dose of dupilumab for adult patients with atopic dermatitis (AD) is 300 mg every other week. At present, it is unknown whether serum dupilumab levels are associated with treatment response or adverse effects. Objectives: To evaluate serum dupilumab levels at 16 weeks of treatment and to explore the association of serum dupilumab levels with treatment response and adverse effects in patients with AD. Design, Setting, and Participants: This clinical, prospective, observational cohort study used data from the prospective BioDay Registry including adult patients with AD who started dupilumab treatment and for whom a serum sample was available at 16 weeks of treatment. All patients were treated according to the BioDay protocol in the University Medical Center Utrecht in the Netherlands. Patients received a loading dose of dupilumab 600 mg subcutaneously, followed by 300 mg every other week. Patients who had a dose adjustment or discontinued treatment before 16 weeks of treatment were excluded. Data analyses were performed from January to June 2022. Main Outcomes and Measures: Disease severity of AD was assessed at baseline and at weeks 16 and 52 using the Eczema Area and Severity Index (EASI). Treatment response was defined as the percent reduction in EASI score vs the baseline score (eg, EASI 90 indicated a 90% reduction) and as an absolute EASI cutoff score of 7 or lower (controlled AD). Adverse effects were recorded during the first year. At 16 weeks, dupilumab serum levels and treatment responses were measured and analyzed. Multivariate logistic regression modeling was used to determine the prediction of response (EASI 90; EASI ≤7) and adverse effects at 52 weeks, with serum dupilumab levels at 16 weeks in the presence of the covariates age and sex. Results: Among the total of 295 patients with AD (mean [SD] age, 41.5 [15.9] years; 170 [57.6%] men), the median (IQR [range]) drug level was 86.6 μg/mL (64.6-110.0 μg/mL [10.1-382.0 μg/mL]) at 16 weeks of treatment. No significant differences were found in serum dupilumab levels between responder statuses (EASI, <50, 50, 75, or 90) at week 16. Multivariate logistic regression analysis showed nonsignificant odds ratios (ORs) for serum dupilumab levels at 16 weeks regarding prediction of long-term response (EASI ≥90: OR, 0.96 [95% CI, 0.90-1.04; P =.34] and EASI ≤7: OR, 1.03 [95% CI, 0.93-1.14; P =.55]) and adverse effects (OR, 1.01 [95% CI, 0.95-1.07; P =.83]). Conclusion and Relevance: This prospective clinical cohort study found a broad range of serum dupilumab levels at 16 weeks of treatment and no association with treatment response and adverse effects during first year of treatment. Response may be dependent on target availability of the interleukin-4 receptor subunit α, with an interpatient variability producing heterogeneity in response..