P508 Pre-operative exposure to tofacitinib is as safe as biologics in patients with ulcerative colitis undergoing colectomy: a multicentre observational study
Authors: Dragoni G , Innocenti T , Amiot A , Castiglione F , Melotti L , Festa S , Savarino E V , Truyens M , Argyriou K , Noviello D , Molnar T , Bouillon V , Bezzio C , Eder P , Fernandes S , Kagramanova A , Armuzzi A , Oliveira R , Viola A , Ribaldone D G , Drygiannakis I , Viganò C , Calella F , Gravina A G , Pugliese D , Chaparro M , Ellul P , Vieujean S , Milla M , Caprioli F ,   “TOFA-poSTOP” Study Group
Published: January 2024

Abstract

Background
Patients with ulcerative colitis (UC) receiving immunomodulators are at substantial risk of colectomy. Since robust evidence regarding the post-operative outcomes of patients treated with anti-JAKs in the pre-operative phase is lacking, we aimed to assess the risk of complications of tofacitinib exposure prior to colectomy in comparison with anti-TNFs, vedolizumab, and ustekinumab.

Methods
A multicentre, retrospective, observational study was conducted across 27 European Centres. Patients with active UC who underwent a total colectomy for medically refractory disease were included. Patients were considered exposed to tofacitinib when they had received the last dose within 4 weeks of surgery and exposed to biologics when they had received the last dose within 12 weeks of surgery. Primary outcome was the occurrence of any complications within 30 days (early) and 90 days (late) after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications (SSC), venous thromboembolic events (VTE), hospital re-admissions and re-do surgery within the same timepoints.

Results
In total, 301 patients were recruited, whose baseline characteristics are reported in Table 1A. No significant differences were found in any outcome across the groups, except for a significantly higher rate of early VTE with anti-TNFs (P=0.047) and of late VTE with VDZ (P=0.03) (Table 1B). In the multivariate analysis, drug class was not associated with a significantly higher risk of any complications both at 30 and 90 days. However, urgent surgery provided a higher risk of any early complications (OR 3.04, 95%CI 1.33-6.96) and late complications (OR 4.57, 95%CI 1.31-15.91), early hospital re-admission (OR 9.90, 95%CI 2.23-43.95) and early re-do surgery (OR 6.86, 95%CI 1.40-33.47). A steroid dose higher than 20 mg of oral prednisone increased the risk of any early complications (OR 2.42, 95%CI 1.14-5.13), early SSC (OR 2.38, 95%CI 1.02-5.55), and early re-do surgery (OR 7.70, 95%CI 1.59-37.14). A higher Charlson comorbidity index increased the risk of any early complications (OR 1.40, 95%CI 1.06-1.84), early infections (OR 1.67, 95%CI 1.17-2.37), early sepsis (OR 2.67, 95%CI 1.46-4.90), and early SSC (OR 1.38, 95%CI 1.04-1.84).

Conclusion
Pre-operative tofacitinib treatment demonstrated a post-operative safety profile comparable to that of biologicals in patients with UC undergoing colectomy. No warning signals were found, with particular regard to VTE and infections. Due to its fast wash-out, tofacitinib could represent an appealing strategy in severe cases in which likelihood of urgent surgery is increased.