S1539 Safety 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. Many require hospitalization and high-risk interventions, such as steroids or surgery. This study evaluates the safety 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 safety outcomes. For patients who received >1 combination, the first combination was used for demographics. Chi-square test was used to analyze categorical variables. 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. 72% failed ≥2 advanced therapies, and 56% of CD patients had prior surgery. Mean combination duration was 12.1 ±12.7 months. Of the 62 that were discontinued, 13 (21%) were due to adverse events. Eleven percent of combinations involved IBD surgery during or ≤12 weeks post-cessation. Overall rates of infection and IBD-related hospitalization were 31% and 13%, respectively. There was one case each (1%) of herpes zoster, C. Difficile infection, and a thrombotic event. At the time of combination start, 41 regimens (33%) included baseline steroid treatment. Compared to no steroids at baseline, regimens with baseline steroid use were associated with significantly greater rates of infection (44% vs 24%, P = 0.02), infection requiring antibiotics (41% vs 17%, P = 0.003), and infection requiring hospitalization (7% vs 0%, P = 0.01), with numerically higher rates of any IBD-related hospitalization (15% vs 4.8%, P = 0.056). Conclusion: In a large specialty IBD center, combination therapy was generally feasible with an acceptable safety profile among patients with severe, treatment-refractory disease. Baseline treatment with steroids at combination initiation was associated with a >2× higher rate of serious infection and >3× higher rate of IBD-related hospitalization, though the latter did not reach statistical significance.