Geographic differences in dupilumab treatment outcomes for atopic dermatitis: A systematic review and meta-regression analysis

Dupilumab, a monoclonal antibody targeting interleukins (IL)-4/IL-13 signaling, demonstrated efficacy in clinical trials for atopic dermatitis. However, real-world variability remains underexplored. A systematic review with meta-regression was conducted to primarily assess geographic influences on dupilumab efficacy measured by percentage eczema area severity index (EASI) reduction and secondly, the presence of adverse events (AEs). Searches were conducted in PubMed, Web of Science, Embase, and Cochrane CENTRAL (PROSPERO:CRD42024579722). Risk of bias was assessed using the Cochrane risk-of-bias tool for nonrandomized studies of interventions (ROBINS-1). Prior to model fitting, articles were subdivided by geographic region. Subsequently, meta-regression analysis was adjusted for geographic region, baseline EASI score, and proportion of female participants. To identify geographic differences, post hoc analysis was performed. Twenty-eight articles were included, covering 509 East Asians, 1604 Northern/Central Europeans, and 4429 Southern Europeans. Baseline EASI scores were highest in East Asians. However, meta-regression revealed that Southern Europeans experienced a 15.33% greater EASI reduction compared with East Asians (95% CI: 6.8%–23.9%, p = 0.0012) and a 10.2% higher reduction compared with Northern/Central Europeans (95% CI: 0.6%–19.8%, p = 0.0434). Additionally, AEs were most frequent in Northern/Central Europeans (95% CI: 0.610–7.633) compared to East Asians (95% CI: 0.145–1.267) and Southern Europeans (95% CI: 0.113–0.484), with geographic variation in AE types. Geographic factors appear to influence dupilumab's clinical outcomes, though the underlying mechanism remains unknown. Trial Registration: PROSPERO: CRD42024579722.