Impact of anti-tumor necrosis factor agents on the risk of colorectal cancer in patients with ulcerative colitis: nationwide French cohort study Short title: Colorectal cancer and anti-TNF in UC

International audienceBackground and Aims: Patients with ulcerative colitis (UC) are at increased risk of colorectal cancer. Anti-tumor necrosis factor agents (anti-TNF) aim to reduce chronic colonic inflammation and may lower the risk of colorectal cancer (CRC), but the impact of anti-TNF exposure has not yet been assessed in population-based cohort studies. The aim of this nationwide study was to assess the risk of CRC in patients with UC exposed to anti-TNF. Methods: Based on the French health insurance database, patients aged 18 years or older with a diagnosis of UC, previously exposed to or initiating immunosuppressive treatment were followed from 1 January 2009 until 31 December 2018. The risk of CRC associated with anti-TNF exposure was assessed using marginal structural Cox proportional hazard models adjusting for baseline and time-varying comorbidities including primary sclerosing cholangitis, UC disease activity, colonoscopic surveillance, and other medications. Results: Among 32,403 patients with UC, 15,542 (48.0%) were exposed to anti-TNF. During a median follow-up of 6.1 years (198,249 person-years), 246 incident CRC occurred (incidence rate per 1000 person-years, 1.24; 95% CI, 1.10-1.41). While the risk of CRC associated with anti-TNF exposure was not decreased in the overall group of patients with UC (HR, 0.85; 95% CI, 0.58-1.26), anti-TNF exposure was associated with a decreased risk of CRC in patients with long-standing colitis (disease duration ≥ 10 years) (HR, 0.41; 95% CI, 0.20-0.86). Conclusions: In a nationwide cohort of patients with UC, anti-TNF exposure was associated with a decreased risk of CRC in patients with long-standing colitis

Specific Norovirus Interaction with Lewis x and Lewis a on Human Intestinal Inflammatory Mucosa during Refractory Inflammatory Bowel Disease

International audienceInflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are progressive diseases affecting millions of people each year. Flare-ups during IBD result in severe mucosal alterations of the small intestine (in CD) and in the colon and rectum (in CD and UC)

Tofacitinib for patients with anti-TNF refractory ulcerative proctitis: a multicenter cohort study from the GETAID

International audienceBackground While ulcerative proctitis (UP) can dramatically impair quality-of-life, treatments efficacy has been poorly investigated in UP as it was historically excluded from phase 2/3 randomized controlled trials in ulcerative colitis. Aim To assess the effectiveness and safety of tofacitinib for the treatment of UP. Methods We conducted a retrospective multicenter study in seventeen GETAID centers including consecutive patients with UP treated with tofacitinib. The primary endpoint was steroid-free remission between week 8 and week 14, defined as a partial Mayo score of 2 (and no individual subscore above 1). Secondary outcomes included clinical response and steroid-free remission after induction and at one year. Results All the 35 enrolled patients previously received anti-TNF therapy and 88.6% were exposed to at least two lines of biologics. At baseline, the median partial Mayo score was 7 (IQR[5.5-7]). After induction (W8-W14), 42.9% and 60.0% of patients achieved steroid-free remission and clinical response, respectively. At one year, the steroid-free clinical remission and clinical response rates were 39.4% and 45.5%, respectively, while 51.2% (17/33) were still receiving tofacitinib treatment. Survival without tofacitinib withdrawal was estimated at 50.4% (95%CI[35.5-71.6]) at one year. Only a lower partial Mayo at baseline was independently associated with remission at induction (Odds ratio (OR) = 0.56 for an increase of 1, 95% confidence interval (95%CI) [0.33-0.95], p = 0.03). Five (14.3%) adverse events were reported with one leading to treatment withdrawal (septic shock secondary to cholecystitis). Conclusion Tofacitinib may offer a therapeutic option for patients with refractory UP

P322 Compared Efficacy of Second-Line Treatments for Ulcerative Colitis After Failure of Vedolizumab in First-Line Treatment: A Retrospective Multicenter Study

Meeting abstract du "19th Congress of ECCO", Stockholm, Suède, 21-24 février, 2024International audienceBackground Vedolizumab is often used as the first-line advanced therapy for patients with moderate to severe ulcerative colitis (UC). There is currently no data reporting the efficacy and safety of second-line treatments after initial vedolizumab failure. The objective of our study was to compare the efficacy of anti-TNF, ustekinumab, and tofacitinib as 2nd line treatment of UC after vedolizumab exposure. Methods We conducted a retrospective multicenter study in 27 French and Belgian centers. All consecutive UC patients treated with vedolizumab between January 2019 and June 2023 as the first line and who received a 2nd line of anti-TNF, ustekinumab or tofacitinib were retrospectively included. The primary outcome was clinical remission at induction (week 14) defined by a clinical partial Mayo score ≤ 2 with no subscore > 1 without investigated treatment withdrawal. Clinical response was defined as a decrease in partial Mayo score of at least 30%. Results Among the 163 patients included, 94 (57.7%) were treated with anti-TNF (infliximab=71 (75.5%), adalimumab=21 (22.3%), and golimumab=2 (2.1%)), 56 (34.4%) with ustekinumab and 13 (7.9%) with tofacitinib. The median duration of the disease prior to second-line initiation was 9.5 months (IQR 16.0-146.0). The median duration of treatment with vedolizumab was 6 months (IQR 3.0-12.0). At week 14, 25/66 (37.9%) patients on infliximab, 7/23 (30.5%) on SQ anti-TNF (adalimumab and golimumab), 25/57 (43.9%) on ustekinumab and 7/13 (53.8%) treated with tofacitinib were in remission (p=0.49, Chi2 test). Response rates were 52.8%, 34.8%, 50.9%, and 53.8%, respectively, for the infliximab, antiTNF SC, ustekinumab, and tofacitinib groups. The survival without treatment discontinuation att 12 months was estimated at 51.6 (95% CI [39.6%-67.2%]) for infliximab, 45.7% (95% CI [28.5%-73.1%]) for SQ anti-TNF, 40.6% (95% CI [27.2%-60.6%]) for ustekinumab and 31.2% (95% CI [12.3%-79.2%]) for tofacitinib (p=0.95, log-rank test). Second-line treatment was discontinued in 41 patients (25.3%) for primary failure, 25 (15.4%) for secondary failure. Colectomy was required in 4 patients (2.5%) during follow-up. Infliximab was discontinued in 12 patients (12.8%) due to adverse reactions, including 6 allergic reactions. Among the 23 patients on SQ anti-TNF (adalimumab and golimumab), 2 required discontinuation (8.7%) due to adverse reactions. One side effect leading to discontinuation occurred with tofacitinib (7.7%) and none with ustekinumab. Conclusion After the failure of vedolizumab as a first-line biologic treatment for UC, the induction efficacy, persistence, and safety of the different second-line treatments seem similar. Current efforts to increase the sample size and strengthen the analysis is ongoing

Efficacy and safety of combination targeted therapies in immune-mediated inflammatory disease: the COMBIO study

International audienceBACKGROUND: Use of a combination of targeted therapies (COMBIO) in patients with refractory/overlapping immune-mediated inflammatory diseases (IMIDs) has increased, but reported data remain scarce. We aimed to assess effectiveness and safety of COMBIO in patients with IMIDs. METHODS: We conducted a French ambispective multicenter cohort study from September 2020 to May 2021, including adults' patients with 1 or 2 IMIDs and treated at least 3-month with COMBIO. RESULTS: Overall, 143 patients were included. The most common IMIDs were Crohn's disease (63.6%), axial spondyloarthritis (37.7%), and ulcerative colitis (14%). Half of patients had only one IMID, of which 60% were Crohn's disease. Mean duration of COMBIO was 274.5±59.3 weeks, and COMBIO persistence at 104 weeks was estimated at 64.1%. The most frequent COMBIOs combined anti-TNF agents with vedolizumab (30%) or ustekinumab (28.7%). Overall, 50% of patients achieved significant and 27% mild-to-moderate improvement in patient-reported outcomes. Extended duration of COMBIO (aOR=1.09; 95% CI: 1.03-1.14; p=0.002) and diagnoses of two IMIDs (aOR=3.46; 95%CI: 1.29-9.26; p=0.013) were associated with significant improvement in patient-reported outcomes. Incidence of serious infection during COMBIO was 4.51 per 100 person-years (95% CI 2.20-8.27) and 5 COMBIOs were discontinued due to adverse events. CONCLUSIONS: COMBIO can be effective and safe in patients with refractory/overlapping IMIDs