Who and how to choose combination therapy for inflammatory bowel disease: a comprehensive expert review

Therapeutic options in inflammatory bowel disease (IBD) have expanded significantly. Patients often experience primary or secondary loss of response to biologics or small molecules therapy. Determining which patients may benefit from combination of two therapies remains a key question.

Combination therapy leverages complementary mechanisms of action, conventionally using tumor necrosis factor antagonists simultaneously with immunosuppressive agents, and more recently using two advanced therapies together. Combination of two advanced therapies has shown promise in two recent randomized trials for improving clinical and endoscopic outcomes while maintaining acceptable safety profiles. Observational studies highlight its potential for refractory disease and complex phenotypes. Guidelines still conservatively recommend monotherapy for IBD patients, even for those at high risk for complications.

Advanced combination therapy (ACT) represents a potential significant advancement in managing IBD, offering treatment options for refractory cases, concomitant immune-mediated diseases and high-risk populations. Nonetheless, further randomized trials and registry data are needed to generate evidence to support broader adoption of this approach. Future research should focus on cost-effectiveness, longer-term treatment strategies and safety to refine its application in clinical practice.