A Scalable Approach to Assess the Safety of Recently Marketed Systemic Treatments for Atopic Dermatitis in Clinical Practice: First Analysis Cycle of a Sequential Monitoring System

Abstract

Targeted systemic immune-modulating drugs to treat atopic dermatitis were highly efficacious in randomized trials. Trials with limited number of subjects leave questions about their safety. We describe a data and analytics structure for the production of timely, high-quality evidence on the comparative safety of recently approved immune-modulating drugs in patients with atopic dermatitis in clinical practice. We established a series of sequential propensity score–balanced cohorts that grow in size with each annual data refresh. Nine health outcomes of interest plus conjunctivitis as a positive tracer outcome were identified. The initial treatment comparison was dupilumab, an IL-4/13 inhibitor, or tralokinumab, an IL-13 inhibitor, versus abrocitinib/upadacitinib, both Jak inhibitors. The first analysis cycle (December 2021–February 2023) compared 269 patients initiating Jak inhibitors and 2650 initiating IL-4/IL-13 inhibitors. Patient characteristics were well-balanced after propensity score matching. Outpatient infections within 180 days occurred in 18% of Jak1 inhibitor initiators versus 12% of dupilumab/tralokinumab initiators (risk ratio = 1.50, 95% confidence interval = 0.96–2.33), whereas acne risks were 7 versus 3%, respectively (risk ratio = 2.29, 95% confidence interval = 0.96–5.46). This sequential monitoring system will produce essential knowledge on the safety of immune-modulating drugs to treat atopic dermatitis on the basis of its growing study size of patients observed in clinical practice.