Comprehensive systematic review and pooled analysis of real-world studies evaluating immunomodulator and biologic therapies for chronic pouchitis treatment

Background and aim: Pouchitis is a common complication after restorative ileal pouch-anal anastomosis following proctocolectomy for ulcerative colitis. Antibiotic-dependent or antibiotic-refractory chronic pouchitis (CP), which is a common cause of pouch failure affecting 15-20% of patients, is challenging to treat. The efficacy of second-line immunomodulator and biologic therapy remains poorly defined. We present a pooled analysis of real-world efficacy data from peer-reviewed full-text manuscripts, focusing on immunomodulator and biologic therapies in CP.

Methods: Embase and PubMed databases were searched for full-text articles describing the treatment of CP. We performed a systematic review and pooled analysis of published studies to assess the efficacy of immunomodulators, including thiopurines and methotrexate, and biologics including antitumor necrosis factor, anti-integrin, and interleukin-12/23 antagonists. Clinical and endoscopic response and remission rates were combined for pooled analyses. Rates of treatment discontinuation and safety were also assessed.

Results: Pooled analysis comprised 20 full-text articles (485 patients). Overall clinical response rate was 46% (95% CI: 35-59%) and clinical remission rate was 35% (95% CI: 21-52%). Overall endoscopic response and remission rates were 41% (95% CI: 18-68%) and 15% (95% CI: 5-39%), respectively. Individual agents' safety profile was reassuring, with vedolizumab being the most favorable.

Conclusion: The real-world efficacy data of immunomodulators in the treatment of CP is insufficient. Vedolizumab and ustekinumab appeared effective and safe for CP, whereas anti-TNFs showed higher rates of adverse events. The high heterogeneity within the studies is attributed to the real-world study design, obfuscating drug efficacy comparisons across the studies. Further studies are required to define the comparative effectiveness of available treatments of CP.