Abstract Background The introduction of biologic agents for the treatment of inflammatory bowel diseases has led to the evolution of treatment targets beyond clinical remission. Recently, disease clearance, defined as the concurrent achievement of clinical, endoscopic, and histologic remission, has emerged as a desirable therapeutic goal in ulcerative colitis. A recent analysis of the EARNEST study demonstrated that mucosal healing in vedolizumab-treated patients with chronic pouchitis correlated with improved clinical outcomes. However, it remains unclear whether achieving disease clearance in patients with chronic inflammatory pouch conditions translates into better clinical outcomes. This study aimed to determine whether disease clearance in patients with chronic inflammatory pouch conditions treated with biologics is associated with improved clinical outcomes. Methods This was an observational, retrospective, multi-centre, multi-national study. We included patients with chronic inflammatory pouch conditions receiving biologic therapy who underwent pouchoscopy demonstrating a normal-appearing pouch (Chicago classification phenotype 1), during which routine biopsies were obtained. Only patients with at least one year of follow-up after the index pouchoscopy were included. Patients were stratified according to histologic findings: normal histology (disease clearance) versus histologic evidence of inflammation. The primary outcomes were biologic treatment persistence, defined as continuation of biologic treatment throughout follow-up, and pouch failure, defined as the need for a defunctioning ileostomy and/or pouch excision. Results Thirty-nine patients met the inclusion criteria. Nineteen had normal pouch histology (disease clearance), while 20 had histologic evidence of inflammation despite normal endoscopic appearance. Biologic agents at the time of the index pouchoscopy included vedolizumab (n = 15), infliximab (n = 11), ustekinumab (n = 7), adalimumab (n = 5), and risankizumab (n = 1). Biologic treatment persistence was similar and high in both groups: 16/19 (84%) among patients with disease clearance and 19/20 (95%) among those with histologic inflammation (p = 0.34). In the disease clearance group, treatment discontinuation occurred in 3 patients, all due to elective treatment de-escalation or safety concerns. One patient with histologic inflammation discontinued therapy due to recurrent pouch inflammation. No cases of pouch failure occurred in either group. Conclusion This study is the first to investigate disease clearance as a potential treatment target in patients with chronic inflammatory pouch disorders. Larger studies with longer follow-up are needed to validate these observations and refine treatment targets in this unique patient population. Conflict of interest: Dr. Ghersin, Itai: No conflict of interest Yeung, Denise: No conflict of interest Koifman, Eduard: No conflict of interest Argyriou, Orestis: No conflict of interest McLaughlin, Simon: No conflict of interest Johnson, Heather: No conflict of interest Sahnan, Kapil: Speaker fees from Takeda, JnJ, Intuitive Ad Board with Medtronic Warusavitarne, Janindra: Other: MSD, Frankenmann, Janssen, Cilag,,Takeda Hart, Ailsa: Grant: Takeda Personal Fees: Abbvie, Amgen, Arena, AZ, Falk, Celltrion, Eli Lilly, Ferring, Genentech/ Roche, GSK, Pfizer, Takeda, Napp, Pharmacosmos, Janssen (J & J), Bristol-Myers Squibb, Gilead, Galapagos, Alfasigma
Ghersin et al. (Thu,) studied this question.