S1473 Comparative Outcomes of Tofacitinib, Vedolizumab and Ustekinumab in Chronic Pouchitis: A Systematic Review and Meta-Analysis

Introduction: Acute pouchitis can develop in up to 70% of patients with ileal pouch anal anastomosis (IPAA) and progress to chronic pouchitis (CP) in about 15% cases. Biologics and immunomodulators have shown promising results in managing CP. The study aimed to assess the efficacy and safety of tofacitinib compared to vedolizumab and ustekinumab for CP in IBD patients. Methods: We searched multiple databases from inception through November 2024 for articles reporting outcomes of tofacitinib, vedolizumab or ustekinumab in patients with CP. Standard meta-analysis methods were employed using the random-effects model, and heterogeneity was studied by I2 statistics. Results: We analyzed 23 (18 retrospective and 5 prospective) studies. Total subjects included were 525 (51.62% males). The clinical response rate was 47.7% [Cl 33.3-62.6%; I2 = 40%] with tofacitinib, 54.9% [Cl 31.5-76.4%; I2 = 90%] with vedolizumab and 73.3% [Cl 50.9-87.9%; I2 = 78%] with ustekinumab. The endoscopic response rate was 51.7% [Cl 37.4-65.7%; I2 = 34%] with tofacitinib, 58.5% [Cl 44.5-71.2%; I2 60%] with vedolizumab and 58.5% [Cl 19.3-57.7; I2 = 71.2%] with ustekinumab. The endoscopic remission rate with tofacitinib, vedolizumab and ustekinumab were 41.2% [Cl 26.6-57.6%; I2 = 0%], 40% [Cl 23.9-58.7%; I2 = 79%] and 36.4% [Cl 19.3-57.7%; I2 = 0%] respectively. The pooled adverse events were higher with tofacitinib, 30.9% [Cl 17.5-48.5; I2 = 24%] compared to 17% [Cl 4.9-44.8%; I2 = 90%] with vedolizumab and 4.6% [Cl 1-17.8%; Cl 58%] with ustekinumab. The discontinuation rate of the drug was highest with tofacitinib 43% [Cl 25-63.1; I2 = 40%] followed by vedolizumab, 30.3% [Cl 20.4-42.5%; I2 = 60%] and then ustekinumab 12.5% [CI 6.1-42.5%; I2 = 0%]. The reason for discontinuation was lack of improvement of symptoms or worsening of pouchitis. Conclusion: Based on this meta-analysis, although not statistically significant, ustekinumab showed maximum clinical response followed by vedolizumab and tofacitinib (73.3% vs 54.9% vs 47.7%). Similarly, endoscopic response rates were more with ustekinumab and vedolizumab compared to tofacitinib (58.5% vs 58.5% vs 41.2%). Tofacitinib was associated with more adverse effects and discontinuation rates as compared to ustekinumab and vedolizumab. Our results suggest that ustekinumab might be a better choice for CP when compared to vedolizumab or tofacitinib. Future direct comparison studies are warranted to establish these findings.