Combining advanced therapies in patients with inflammatory bowel disease and extraintestinal manifestations or associated immune-mediated diseases: Who, what, when and at what cost?

Abstract

Management of extraintestinal manifestations (EIMs) and concomitant immune-mediated inflammatory diseases (IMIDs) in patients with inflammatory bowel disease (IBD) represents a significant clinical challenge, often requiring the combination of advanced therapies to achieve adequate disease control. This review aims to provide a comprehensive and practical framework for the implementation of dual advanced therapy (DAT) in this complex patient population.We performed a narrative review of randomised trials, real-world cohorts and case series on combinations of biologics and small molecules in IBD with EIMs/IMIDs, appraising mechanistic complementarity, safety and economic implications.Although evidence remains limited, DAT appears appropriate for selected profiles: refractory IBD with active EIMs, concomitant IMIDs with divergent tissue responses and 'bridge' strategies during class switching. Combinations leveraging non-overlapping pathways (eg, anti-tumour necrosis factor with vedolizumab or ustekinumab; Janus Kinase (JAK) inhibitors with gut-selective or cytokine-targeted agents) are most promising. We outline monitoring targets by domain and a safety checklist (infections, malignancy, thromboembolism, vaccination).This review translates heterogeneous data into a pragmatic Who/What/When/Cost framework to guide DAT in IBD with EIMs/IMIDs and delineates research priorities for cross-organ outcomes and long-term safety.