Clinical Outcomes During Concurrent Dupilumab and Advanced Immune-Modifying Therapy: A Real-World Cohort Study.

BACKGROUND: The use of dual advanced therapy is increasing among patients with overlapping immune-mediated diseases. This is particularly relevant in patients with inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE), where dupilumab may be added to an existing IBD-directed biologic regimen. However, real-world safety data regarding concomitant dupilumab and advanced immune-modifying therapies commonly used in IBD remain limited. METHODS: We performed a retrospective cohort study using the All of Us Research Program Controlled Tier dataset. Adults receiving advanced immune-modifying therapies commonly used in IBD, including biologics, Janus kinase inhibitors, and sphingosine-1-phosphate receptor modulators, were categorized by documented dupilumab exposure. Participants designated as dual-exposed were required to have documented overlap between dupilumab and advanced therapy, with the index date defined as the first date of concurrent exposure. Outcomes evaluated included hospitalization, emergency department (ED) utilization, and selected infectious outcomes, including pneumonia, sepsis, cellulitis, and herpes zoster, identified using standardized diagnosis codes. RESULTS: Among 4605 participants receiving advanced immune-modifying therapies, 21 (0.5%) had documented dupilumab exposure, of whom 12 (57.1%) had overlapping treatment periods and comprised the concurrent-therapy cohort. These participants were compared with 4458 individuals receiving advanced immune-modifying therapy alone. There were 2 versus 900 selected infectious outcomes, 3 versus 2111 hospitalizations, and 3 versus 2198 emergency department visits in the concurrent-therapy and comparator groups, respectively. Concurrent dupilumab exposure was not associated with statistically significant differences in rates of selected infectious outcomes (IRR, 2.87; 95% CI 0.35-10.40; P = 0.16), hospitalization (IRR, 1.50; 95% CI 0.31-4.40; P = 0.46), or emergency department utilization (IRR, 1.65; 95% CI 0.34-4.82; P = 0.44). CONCLUSIONS: Concomitant dupilumab exposure among patients receiving advanced immune-modifying therapies commonly used in IBD was uncommon but was not associated with statistically significant differences in rates of selected infectious outcomes, hospitalization, or emergency department utilization in this national real-world cohort. Although limited by the small number of dual-exposed participants, these findings provide preliminary real-world data and support further investigation in larger disease-specific populations, particularly among patients with overlapping IBD and EoE, in whom the present study was not sufficiently powered to draw definitive conclusions regarding comparative safety.