Are Small Molecules Effective in Treating Inflammatory Pouch Disorders Following Ileal Pouch-Anal Anastomosis for Ulcerative Colitis? Here is Where We Stand

Ulcerative colitis (UC) management encompasses conventional and advanced treatments, including biological therapy and small molecules. Surgery, particularly in the form of ileal pouch-anal anastomosis (IPAA), is indicated in cases of refractory/severe disease. IPAA can lead to acute complications (e.g., acute pouchitis) as well as late complications, including chronic inflammatory disorders of the pouch. Chronic pouchitis, including the antibiotic-dependent (CADP) and antibiotic-refractory (CARP) forms, represents a significant and current therapeutic challenge due to the substantial need for evidence regarding viable treatment options. Biological therapies have shown promising results, with infliximab, adalimumab, ustekinumab, and vedolizumab demonstrating some efficacy in chronic pouchitis; however, robust randomized clinical trials are only available for vedolizumab. This narrative review focuses on the evidence concerning small molecules in chronic pouchitis, specifically Janus kinase (JAK) inhibitors and sphingosine-1-phosphate receptor (S1P-R) modulators. According to the preliminary studies and reports, Tofacitinib shows a potential effectiveness in CARP. Upadacitinib presents variable outcomes from the case series, necessitating further evaluation. Filgotinib and ozanimod demonstrate anecdotal efficacy. This review underscores the need for high-quality studies and real-world registries to develop robust guidelines for advanced therapies in post-IPAA inflammatory disorders, supported by vigilant clinical monitoring and ongoing education from international IBD specialist societies.