Real-World Effectiveness and Safety of Advanced Combination Treatment in Patients with Refractory Inflammatory Bowel Disease

INTRODUCTION: Advanced combination treatment (ACT) pairs two advanced therapies with distinct mechanisms of action for inflammatory bowel disease (IBD) that has not responded to single agents. However, real-world evidence on individual regimens remains limited. METHODS: We retrospectively identified all ACT courses at a tertiary centre in Abu Dhabi (June 2021 to May 2026). A course required the concurrent use of two advanced therapies with documented clinical intent, with no minimum duration. Disease activity, laboratory values, endoscopic findings and therapeutic drug monitoring were recorded prospectively in the centre's IBD registry, and every rate is reported over the whole cohort. The primary outcome was composite remission (clinical and biochemical remission together); endoscopic outcomes were reported separately. RESULTS: A total of 16 patients (11 Crohn's disease, 5 ulcerative colitis) received 21 courses across 12 regimens; 13 (81%) were Emirati. The commonest combinations paired a selective anti-interleukin-23 agent with a Janus kinase inhibitor (10 courses) or with an anti-tumour necrosis factor agent (5). Patients had failed a median of four prior advanced therapies, and the median course duration was 218 days. Composite remission was achieved in 11 of 21 courses (52%, 95% confidence interval [CI] 30-74%; 11 of 16 patients), clinical remission in 15 of 21 (71%) and biochemical remission in 11 of 21 (52%); 14 of 21 (67%) were corticosteroid-free. Clinically timed endoscopic reassessment in 14 courses showed endoscopic remission in five. Twelve courses (57%) were discontinued, seven for treatment failure. One serious adverse event, a urinary tract infection requiring admission, occurred during combination therapy. CONCLUSION: ACT achieved composite remission in just over half of courses in this multi-refractory cohort, with one serious adverse event. These findings support consideration of ACT in carefully selected multi-refractory patients under close monitoring; further real-world data on individual regimens are needed to guide the choice of combination.