S1475 Exploring the Role of Tofacitinib in Managing Chronic Pouchitis: A Systematic Review and Meta-Analysis

Introduction: Tofacitinib, a Janus kinase inhibitor has been used for induction and maintenance of remission in patients with moderate to severe ulcerative colitis. However, recent studies have shown promising results in management of chronic pouchitis (CP) with tofacitinib. We performed a pooled analysis of the efficacy and safety of tofacitinib for CP in patients with inflammatory bowel disease. Methods: We searched multiple databases from inception through November 2024 for articles reporting outcomes of tofacitinib 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 8 studies including 3 prospective and 5 retrospective studies involving 99 subjects (55.56% males and mean age of 37.46 years). The mean duration of reassessment after initiating tofacitinib was 2.5 months. The pooled clinical response rate with tofacitinib was 47.7% [Cl 33.3-62.6%; I2 = 40%]. The endoscopic response rate and endoscopic remission rate were 51.7% [Cl 37.4-65.7%; I2 = 34%] and 41.2% [Cl 26.6-57.6%; I2 = 0%] respectively. Clinical PDAI (Pouchitis Disease Activity Index) score improved markedly post-tofacitinib (Pre: 3.35 [Cl 2.9-3.7; I2 = 68%] vs Post: 2.0 [Cl 1.59-2.4; Cl = 0%] with SD 0.80 ± 0.19 and P < 0.001). There was a significant reduction in endoscopic PDAI score with treatment (Pre: 4.5 [Cl 3.7-5.2; I2 = 84%] vs Post: 2.5 [Cl 1.7-3.3; Cl = 64%] with SD 0.99 ± 0.25 and P < 0.001). Total PDAI scores also showed significant improvement with tofacitinib (Pre: 7.4 [Cl 5.3-9.6; I2 = 96%] vs Post: 4.3 [Cl 2.8-5.9; Cl = 84%] with SD 1.30 ± 0.37 and P < 0.001). The pooled adverse events were 30.9% [Cl 17.5-48.5; I2 = 24%]. The pooled rate of lack of symptomatic improvement was 47% [Cl 28.8-66.0%; I2 = 32%] and worsening of pouchitis was 56.6% [Cl 7-95.8%; I2 = 82%]. The discontinuation rate of tofacitinib was 43% [Cl 25-63.1; I2 = 40%]. Conclusion: Based on this meta-analysis, tofacitinib caused statistically significant changes in clinical, endoscopic and total PDAI scores with favorable response and remission rates. Although there are significant rates of adverse events, worsening of symptoms and discontinuation, this is similar to other biologic therapies and in some instances less frequent. Future studies are required to evaluate the long-term safety profile of tofacitinib before considering it as an effective alternative for the treatment of CP.