34927 Adverse events associated with dupilumab in the WHO pharmacovigilance

Abstract

Background: Dupilumab, an anti-IL-4/13, is approved to treat atopic dermatitis and asthma with a favourable adverse event profile in a selected population from trials. Objective: To assess and describe the spectrum of dupilumab adverse events reported in a pharmacovigilance database. Methods: We used Vigibase, the WHO pharmacovigilance database, and included all physician reports with dupilumab as suspected cause. We used the information component (IC), an indicator for disproportionate reporting, and IC025, the lower limit of its 95% credibility interval. IC025>0 is the statistical significance threshold used in Vigibase, meaning that the adverse event is associated with dupilumab. Results: In 4894 physician reports, the median age was 44 years and 1884 patients were female (38%). The most common adverse events were skin disorders, with 53 (32%) associated adverse events, mostly related to atopic dermatitis, alopecia areata (IC025 4.1) and psoriasis-like eruptions (IC025 2.2). Eye disorders displayed 35 (21%) associated adverse events, mainly related to conjunctivitis and keratitis symptoms, infections and infestations, 14 adverse events (8%), mainly related to herpes infections. Musculoskeletal disorders displayed 8 adverse events (5%), blood and lymphatic disorders 5 adverse events, (3%) and immune disorders 5 adverse events (3%), including serum sickness (IC025 3.9). We found no association with serious infections, vascular events, psychiatric disorders or cancer, with the exception of cutaneous T cell lymphoma (IC025 2.8). Discussion: With few serious adverse events in routine clinical use, we confirm dupilumab favorable safety observed in clinical trials, such as the good overall benefit/risk ratio of dupilumab.