S1720 Comparative Effectiveness of JAK Inhibitors vs Traditional Therapies in Moderate-to-Severe Ulcerative Colitis

Introduction: The therapeutic landscape for moderate-to-severe ulcerative colitis (UC) has evolved with the emergence of Janus kinase (JAK) inhibitors, such as tofacitinib and upadacitinib. Despite their targeted mechanisms, the comparative efficacy and safety of JAK inhibitors relative to established biologics like infliximab and adalimumab remain inadequately defined. To compare the clinical effectiveness and safety of JAK inhibitors vs traditional biologic therapies for induction and maintenance of remission in moderate-to-severe UC. Methods: We performed a systematic review and network meta-analysis using R (packages: netmeta, meta) on Phase 3 randomized controlled trials (RCTs) published up to May 2024. Studies evaluating tofacitinib, upadacitinib, infliximab, adalimumab, vedolizumab, and ustekinumab were included. Primary outcomes were induction and maintenance of clinical remission. Secondary outcomes included endoscopic improvement and adverse event (AE) rates. Surface under the cumulative ranking (SUCRA) scores were used to rank efficacy. Results: Thirty-six RCTs involving 14,270 patients were analyzed. Upadacitinib ranked highest for induction of clinical remission (SUCRA 99.6%), followed by infliximab and vedolizumab. For maintenance of remission, upadacitinib again ranked first (93.1%), outperforming tofacitinib and infliximab. Upadacitinib and tofacitinib achieved superior histological and endoscopic remission compared to traditional agents. However, upadacitinib also showed the highest incidence of adverse events, predominantly nasopharyngitis and elevated liver enzymes, though serious infections were infrequent. Vedolizumab exhibited the most favorable safety profile. Conclusion: JAK inhibitors, particularly upadacitinib, demonstrate superior efficacy over traditional biologics in inducing and maintaining remission in moderate-to-severe UC. Nonetheless, their safety profile necessitates careful patient selection. These findings underscore the importance of individualized therapy balancing effectiveness with tolerability. This comparative analysis can aid clinicians in treatment stratification and supports the integration of JAK inhibitors into contemporary UC management algorithms.