INTRODUCTION: We aimed to evaluate the real-world effectiveness and safety of tofacitinib for the treatment of ulcerative colitis (UC). METHODS: REMIT-UC is a Canadian multicenter cohort study. Standardized data collection was performed on 334 consecutive adult outpatients with UC treated with tofacitinib. The primary outcomes were achievement of clinical and endoscopic remission. Safety outcomes were reported using incidence rates (events/100 patient-years of exposure). A multivariable Cox proportional hazards model was used to evaluate predictors of loss of response after tofacitinib dose de-escalation to 5 mg twice daily (BID). RESULTS: Clinical remission was achieved by 35.3% (106/300), 36.0% (104/289), and 35.2% (93/264) of patients at weeks 12, 24, and 52, respectively. Endoscopic remission was achieved by 18.5% (15/81), 23.0% (28/122), and 25.7% (35/136) of patients at weeks 12, 24, and 52, respectively. Incidence of serious infections, herpes zoster, and venous thromboembolism were 2.1 [0.9–4.2], 0.5 [0.1–1.9], and 1.1 [0.3–2.7], respectively. Among responders, 44.5% (109/245) lost response during follow-up, which was recaptured in 54.9% (39/71) of patients who re-escalated to 10 mg BID. Patients with a baseline Mayo endoscopic score of 3 (adjusted hazard ratio 3.60 [95% confidence interval: 1.70–7.62]) and prior biologic failure (adjusted hazard ratio 3.89 [95% confidence interval: 1.28–11.86]) were at a higher risk for losing response after dose reduction. DISCUSSION: One-third of patients with UC treated with tofacitinib achieved clinical remission with few serious adverse events. However, half of patients lost response with de-escalation, which was only partially recaptured with increasing the maintenance dose. Those with negative prognostic factors should be counselled about the risks and benefits of continuing high doses of tofacitinib.

INTRODUCTION: Fecal microbiota transplantation (FMT) has shown promise at inducing remission in ulcerative colitis. This study is the first of its kind to evaluate the efficacy and safety of FMT at inducing remission in Crohn's disease (CD). METHODS: This double-blind, placebo-controlled trial was conducted in 3 Canadian academic centers; randomized patients with mild-to-moderate CD received FMT or placebo. The first treatment was administered by colonoscopy followed by weekly oral capsules for 7 weeks. Primary end point was clinical and endoscopic remission at week 8. Secondary outcomes included clinical and endoscopic response, adverse events, and health-related quality of life using generic and disease-specific instruments. RESULTS: From July 2017 to June 2021, 21 and 13 patients were randomized to FMT and placebo groups, respectively. The trial terminated early due to futility. At week 8, 0% (0/15) of patients in the FMT group versus 8.3% (1/11) in the placebo group reached the primary end point of combined clinical and endoscopic remission as per protocol analysis. There were no differences between the groups in clinical or endoscopic responses. One patient in each group had worsening of CD. Although both groups experienced statistically significant improvements in health-related quality of life, only the FMT group had a significant decrease in activity impairment. Although there were no significant changes in microbial diversity or composition, patients who achieved clinical response became more similar to their donors in stool microbial composition. DISCUSSION: FMT was not effective at inducing clinical and endoscopic remission in CD using the FMT regimen in this study. Future studies may use other strategies to enhance treatment response, including longer intervention, antibiotic pretreatment, optimized donor-recipient pairing, and concomitant anti-inflammatory diet, and biologic or small molecule therapies.

Elderly-onset inflammatory bowel disease [IBD] patients exhibit a distinct natural history compared to younger IBD patients, with unique disease phenotypes, differential responses to therapy, and increased surgical morbidity and mortality. Despite the foreseeable high demand for personalized medicine and specialized IBD care in the elderly, current paradigms of IBD management fail to capture the required nuances of care for elderly-onset IBD patients. Our review postulates the roles of systemic and mucosal immunosenescence, inflammageing and a dysbiotic microbial ecosystem in the pathophysiology of elderly-onset IBD. Ultimately, a better understanding of elderly-onset IBD can lead to improved patient outcomes and the tailoring of future preventative and treatment strategies.

Background: In patients with inflammatory bowel disease (IBD), frailty is independently associated with mortality and morbidity. Objectives: This study aimed to extend this work to determine the association between the clinical frailty scale (CFS), handgrip strength (HGS), and malnutrition with IBD-related hospitalizations and surgeries. Design: IBD patients ⩾18 years of age were prospectively enrolled from two ambulatory care clinics in Alberta, Canada. Methods: Frailty was defined as a CFS score ⩾4, dynapenia as HGS < 16 kg for females and <27 kg for males, malnutrition using the subjective global assessment (SGA), and the risk of malnutrition using either the abridged patient-generated SGA (abPG-SGA), or the Saskatchewan Inflammatory Bowel Disease Nutrition Risk Tool (SaskIBD-NRT). Logarithm relative hazard graphs and multivariable logistic regression models adjusting for relevant confounders were constructed. Results: One hundred sixty-one patients (35% ulcerative colitis, 65% Crohn’s disease) with a mean age of 42.2 (±15.9) years were followed over a mean period of 43.9 (±10.1) months. Twenty-seven patients were hospitalized, and 13 patients underwent IBD-related surgeries following baseline. While the CFS (aHR 1.34; p = 0.61) and SGA (aHR 0.81; p = 0.69) did not independently predict IBD-related hospitalizations, decreased HGS (aHR 3.96; p = 0.03), increased abPG-SGA score (aHR 1.07; p = 0.03) and a SaskIBD-NRT ⩾ 5 (aHR 4.49; p = 0.02) did. No variable was independently associated with IBD-related surgeries. Conclusion: HGS, the abPG-SGA, and the SaskIBD-NRT were independently associated with an increased risk of IBD-related hospitalizations. Future studies should aim to validate other frailty assessments in the IBD population in order to better tailor care for all IBD patients.

Background: Tofacitinib is a rapidly acting Janus kinase (JAK) inhibitor with increasing evidence of effectiveness in patients with acute severe ulcerative colitis (ASUC). However, there are scarce prospective data analyzing the efficacy and rapidity of action in hospitalized ASUC. Methods: The TRIUMPH study is a prospective open-label interventional trial of tofacitinib in hospitalized patients with ASUC conducted in 5 hospitals across Canada (Clinicaltrials.gov: NCT04925973). Eligible participants included biologic-naïve and experienced patients with ASUC refractory to 3 days of intravenous (IV) corticosteroids (Modified Truelove-Witts Severity Index [MTWSI] > 10 despite steroids). Participants were treated with tofacitinib 10 mg twice daily and assessed daily while in hospital. The primary outcome was day 7 clinical response (MTWSI reduction of > 3 from baseline and ≤ 10). Results: Among 24 subjects, 33.3% (8/24) had previous anti-TNF failure. Day 7 clinical response was achieved in 58.3% (14/24). The mean number of days to achieve clinical response was 2.4 (SD 1.3). Marked reduction in C-reactive protein was observed in responders within the first two days after tofacitinib initiation compared to nonresponders. Colectomy occurred in 25% (6/24) by 6 months, with no additional colectomy beyond this time point. Five participants reported a total of 13 adverse events. Conclusions: Tofacitinib is an effective rescue therapy in hospitalized patients with steroid-refractory ASUC. Randomized controlled trials are warranted to compare JAK inhibitors with other rescue therapies, including infliximab in steroid-refractory ASUC (Clinicaltrials.gov: NCT04925973).

Background: Approximately 70% of primary sclerosing cholangitis (PSC) patients have inflammatory bowel disease (IBD). The IBD therapies currently used to treat PSC-IBD patients have side effects and can be costly. Oral vancomycin (OV)—a safe, economical, and convenient therapy—has been reported to be a salvage therapy in refractory PSC-IBD patients. This systematic review aims to summarize the current literature regarding the effectiveness and safety of OV to treat IBD in PSC patients. Methods: A systematic literature review of Scopus, Embase, Web of Science, MEDLINE, and CINAHL was performed until March 2024. The Murad scale, Newcastle-Ottawa scale, and Cochrane Collaboration Risk of Bias Tool were used to determine the quality of the case reports and case series, cohort studies, and randomized controlled trial (RCT), respectively. The outcomes sought were response or remission across clinical, biochemical, endoscopic, and histological parameters. Results: Of the 1725 published studies, we identified 9 case reports, 7 case series, 3 cohort studies, and 1 RCT. Most studies reported an improvement in clinical IBD symptoms such as diarrhea and hematochezia. Fewer publications provided supporting objective data in the form of fecal calprotectin, endoscopic Mayo scores, and histology. There were no reports of vancomycin-resistant enterococci infections. Conclusions: Oral vancomycin appears safe and effective to treat IBD in a subset of PSC patients. Future studies would benefit from prospective data collection incorporating standardized symptomatic, endoscopic, and histologic indices. Ultimately, a well-powered RCT is needed to better assess the effectiveness, safety, and durability of OV therapy.