S1540 Effectiveness of Combination Biologic and/or Small Molecule Therapies in Inflammatory Bowel Disease: A Single Center Analysis

Introduction: Despite an increasing variety of treatment options, many inflammatory bowel disease (IBD) patients do not achieve therapy goals. Plateauing efficacy of single-agent regimens is commonly reported even after therapy optimization. This study evaluates the effectiveness of combination regimens including newer agents in adult IBD patients. Methods: Adult patients with Crohn’s disease (CD) or ulcerative colitis (UC) treated ≥6 weeks with 2 concomitant biologic and/or small molecule therapies (including TNF antagonists [TNF-a], anti-integrin agents, IL-(12/)23 inhibitors [IL-12/23i], JAK inhibitors [JAKi], or S1P receptor modulators) were identified via clinical practice and an institutional IBD patient database. Data were obtained on demographics, treatment, and disease activity. For patients who received >1 combination, the first combination was used for demographics. Descriptive statistics are used to report observational outcomes. Results: 125 regimens among 102 patients (64 CD, 38 UC) were analyzed with 49% women, 9% Black, and 11% Hispanic; mean age was 40 ± 17 years. Average disease duration by combination start was 14 ± 12 years. 92% received prior steroids and 88% prior TNF-a. Seventy-two percent failed ≥2 advanced therapies, and 56% of CD patients had prior surgery. Mean baseline Harvey-Bradshaw Index (HBI) and Partial Mayo (PM) were 7 ± 7 and 4 ± 2, respectively. At baseline, the mean Simple Endoscopic Score for CD was 13 ± 10, and 91% of UC patients had a Mayo score of 2 or 3. Mean combination duration was 12.1 ± 12.7 months. Combination IL-12/23i + JAKi (52%) was the most frequent regimen. Among patients with baseline and follow-up HBI/PM data, 74% achieved clinical response and 69% remission. Among patients with endoscopic data, 71% (27/38) achieved improvement and 33% (13/42) remission. Mean time to clinical and endoscopic remission was 4.8 ± 4.9 and 10.8 ± 11.7 months, respectively. Combinations containing JAKi trended towards the greatest rates of clinical (75%) and endoscopic (40%) remission. Active perianal disease or other extraintestinal manifestations (EIM) improved with 63% and 65% of combinations, respectively. Among patients with elevated CRP (n = 40) or fecal calprotectin (n = 40), 60% and 63% achieved normalization. Conclusion: In a large specialty IBD center, combination therapy was feasible and effective. No distinct combination achieved significantly superior outcomes. Targeting multiple pathways active in IBD may achieve greater effectiveness than single-agent regimens.