S1693 Efficacy of Biologics and Small Molecules for Maintenance of Response and Remission in Fistulizing Crohn’s Disease: A Network Meta-Analysis of Randomized Controlled Trials

Introduction: Fistulizing Crohn’s disease (FCD) is a debilitating complication associated with high rates of recurrence and long-term morbidity. While the induction of fistula closure is essential, sustained maintenance of remission and response remains a key therapeutic challenge. Despite the availability of biologics and small molecules, the comparative efficacy of these agents in sustaining fistula healing over extended follow-up periods remains poorly defined. This network meta-analysis (NMA) was performed to evaluate and rank the efficacy of advanced therapies for maintaining clinical remission and response in patients with FCD. Methods: We performed a systematic review and frequentist random-effects NMA of randomized controlled trials evaluating biologics and small molecules for maintenance therapy in FCD over a 12-month period. Fistula remission was defined as complete closure of all external draining fistulas, and response as a ≥50% reduction in the number of draining fistulas from baseline without new fistula formation. A frequentist random-effects NMA was performed using the netmeta package in R to estimate the odds ratios and P-scores for treatment ranking. Results: Ten RCTs were included to evaluate the efficacy of 9 advanced therapies for maintaining fistula remission and response with a mean follow-up duration of 13.5 months. Perianal FCD was the predominant phenotype observed in the study population. Adalimumab (OR 3.34; 95% CI 1.24-9.01), Infliximab 5 mg/kg (OR 2.80; 95% CI 1.50-5.21), and ustekinumab (OR 6.50; 95% CI 1.09-38.8) significantly increased the odds of maintaining complete fistula remission compared to placebo. Only 5 studies reported maintenance of fistula response; infliximab 5 mg/kg showed significant improvement with fistula response (OR 1.88; 95% CI 1.15-3.07); however, upadacitinib 15 mg (OR 9.86; 95% CI 0.47-206) and upadacitinib 30 mg (OR 7.67; 95% CI 0.35-166) demonstrated favorable trends, although the differences did not reach statistical significance. Vedolizumab did not demonstrate superiority over placebo in the maintenance of either fistula remission or response. Conclusion: This NMA supports the use of anti-TNF agents and ustekinumab for maintaining fistula remission. These findings support the continued use of select biologics for long-term fistula management, though data on newer IL-23 inhibitors remain limited, highlighting the need for further studies to define their role in maintenance therapy.