S1558 Long-Term Outcomes of Biologics in Ulcerative Colitis: A Network Meta-Analysis

Introduction: Biologic therapies have revolutionized the management of ulcerative colitis (UC), yet real-world and trial-based evidence on their long-term comparative effectiveness and safety remains limited. Understanding sustained clinical remission, mucosal healing, and long-term tolerability is essential to optimizing treatment algorithms. To compare the long-term efficacy and safety of approved biologics and small molecules for moderate-to-severe UC using a network meta-analysis of maintenance-phase randomized controlled trials (RCTs). Methods: A systematic review and network meta-analysis were performed per PRISMA-NMA standards. MEDLINE, EMBASE, and CENTRAL databases were searched through April 2024. Phase 3 RCTs evaluating maintenance therapy (≥12 months) with infliximab, adalimumab, vedolizumab, ustekinumab, tofacitinib, or upadacitinib were included. Primary outcome: maintenance of clinical remission. Secondary outcomes: endoscopic and histologic remission, and serious adverse events (SAEs). Analysis was conducted in R using netmeta and gemtc packages. Results: Twenty-one trials (N = 8,935) were included. Upadacitinib ranked highest for maintenance of clinical remission (SUCRA 93.1%), followed by ustekinumab and vedolizumab. Endoscopic and histologic remission were most sustained with upadacitinib and ustekinumab. Vedolizumab demonstrated the lowest SAE rates (SUCRA 89.7%), followed by ustekinumab and infliximab. Tofacitinib showed favorable efficacy but had higher discontinuation due to adverse events. Subgroup analysis suggested that biologic-naïve patients had better long-term outcomes with infliximab and ustekinumab, while those with prior biologic exposure responded better to upadacitinib. Conclusion: Upadacitinib and ustekinumab appear most effective in sustaining long-term clinical and mucosal remission in moderate-to-severe UC. Vedolizumab remains the safest long-term option, reinforcing its role in risk-averse patients. These findings support a personalized, long-term strategy for biologic selection in UC and provide a comprehensive reference for clinical decision-making and guideline development.