Abstract Background Restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) is the reference standard surgical procedure for patients with Ulcerative Colitis (UC). Conflicting data exist regarding the relationship between pre-operative advanced therapy use and development of pouchitis, even though in pouchitis rates after IPAA has been recorded over time 1. We aimed to evaluate long-term pouchitis-free survival in a large cohort of UC patients who underwent IPAA. Methods We conducted a retrospective multicenter study involving 15 centers from the Latium Net and affiliated with IG-IBD. Patients with UC who underwent IPAA and had ileostomy closure between January 1980 and December 2024 were included. Relevant variables were collected, including clinical and demographic data, pre-colectomy treatments, centre and type of surgery, and follow-up data of at least one year. For the analysis, using the date of ileostomy closure as baseline, the entire cohort was divided into three temporal subgroups, defined according to the years advanced therapies for UC became commercially available in Italy: Infliximab in 2006 and Vedolizumab in 2016. Results A total of 237 patients were enrolled: 67 underwent surgery before 2006 (cohort 1), 76 between 2006 and 2016 (cohort 2), and 94 after 2016 (cohort 3). At colectomy 19.4% had at least one extra-intestinal manifestation, and the prevalence increased significantly over time (from 10.4% to 28.7%, p = 0.01). Pre-operative exposure to corticosteroids also increased across periods (from 85,1% to 92,6%, p = 0.025). Conversely, the proportion of patients naïve to advanced therapies decreased (from 94% to 17%, p 0.001). The rate of elective surgical procedures rose from 52.2% to 70.2% (p 0.001) and the approach with a three-stage procedure increased over time (p = 0.002). After a median follow-up of 3.1 years, up to 50% of patients experienced at least one episode of pouchitis. Pouchitis-free survival at one year declined from 92.54% in cohort 1 to 64.65% in cohort 3, p 0001. Overall, 98 patients (41.3%) developed chronic pouchitis; of these 22.3% with antibiotic-dependent and 11% exhibited a Crohn-like phenotype, yielding an incidence rate of 3.49 per 100 person-years. Among patients with chronic pouchitis, 81 patients (82.7%) required an advanced therapy, with a significant increase in the later cohorts (p 0.001). Finally, 10.1% of the entire cohort required a definitive ileostomy and 0.8% underwent surgical pouch revision. Conclusion Over time, we observed a reduced probability of pouchitis-free survival, a progressive shortening of the time to the first pouchitis episode and an increased need for advanced therapy to manage chronic pouchitis in recent years. Reference: 1. Fischman M, Godny L, Friedenberg A, et al. Factors Associated With Biologic Therapy After Ileal Pouch-Anal Anastomosis in Patients With Ulcerative Colitis. Inflamm Bowel Dis. 2024 Nov 14:izae272. doi: 10.1093/ibd/izae272. Epub ahead of print. PMID: 39540419. Conflict of interest: Cuccia, Giuseppe: none Aratari, Annalisa: Consultant or Advisory board member (in the last two years) for Takeda,Abbvie,Pfizer,Galapagos Zerboni, Giulia: none Festa, Stefano: Personal Fees: Consultant and/or Advisory board member for: Takeda, Johnson & Johnson, Pfizer, Galapagos, Abbvie, Ferring, Eli Lilly Del Gaudio, Angelo: none Marafini, Irene: Irene Marafini served as advisory board member for Abbvie, Eli Lilly, Galapagos and received speaker honoraria from Abbvie and Eli Lilly Bracci, Fiametta: none Falasco, Giuliano: none Di Cola, Simone: None Pagnini, Cristiano: none Laterza, Lucrezia: Employment full time / part time None Research Grant (P.I., collaborator or consultant pending and received grants) None Other research support None Speakers Bureau / Honoraria Company name/Lecturer Abivax, Biocure Ownership interest (stock, stock-options, patent or intellectual property None Consultant / advisory board Actial Farmaceutica, Abbvie, Lilly, J & J Baccini, Flavia: None Zampaletta, Costantino: none Mancone, Roberto: none Vincoli, Giuseppina: none Parisio, Laura: None Caldaro, Tamara: None Monterubbianesi, Rita: none Merli, Manuela: None Di Paolo, Maria Carla: None Magiotta, Ambra: none Giovannone, Maurizio: None Scarozza, Patrizio: No Conflict of Interest to declare Bragazzi, Maria Consiglia: none Cesarini, Monica: none D’Arcangelo, Giulia: None Scaldaferri, Franco: Consultancy fee/board for Janseen, Takeda, Pfizer, MSD, Sandoz, Galapagos, Celltrion, Ferring, Abbvie, Lilly, Alfasigma, Abivax Fiorino, Gionata: Personal Fees: Takeda, Johnson&Johnson, Alfasigma, AbbVie, Celltrion, Pfizer, Sandoz, Abivax, Lilly, STADA Pugliese, Daniela: Consultant/Lectures fees from: AbbVie, Takeda, Johnson, Pfizer, Alfasigma, MSD, Lilly, Celltrion.
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