Jeffrey D. McCurdy

Background: Inflammatory Bowel Diseases (IBD) are challenging conditions to manage due to the heterogeneity of the disease, diverse treatment options, and nuances of care over a range of ages. Clinical care pathways (CCPs) developed by experts enable health care providers (HCPs) to deliver standardized, high-quality, evidence-based care. In order to remain useful and valuable, these pathways need to evolve alongside changing treatment recommendations. Standardizing IBD care is a priority of Crohn’s Colitis Canada’s Promoting Access and Care through Centres of Excellence (PACE) network. Aim: To describe the process of nationalizing IBD CCP’s, including development, standardization, maintenance, and dissemination. Methods: This project was based on a previously developed structured framework for review and maintenance. The CCP team consisted of a leadership group, advisory council and a working group with diverse representation from the country and areas of expertise. The work was tracked with a database with coordination completed by staff of the national organization. Results: The nationalization process lasted 14 months, with input from 23 HCPs from 14 academic and community institutions across Canada. Sixteen CCPs for IBD care were developed and approved by the CCP team. Challenges encountered included outdated guidelines, differing clinical opinions, and busy clinical schedules of the team members. Translation into French is complete. Support of Crohn’s and Colitis Canada was invaluable. Conclusion: Despite anticipated challenges, 16 CCPs received approval from the advisory council and are publicly available to HCPs across Canada. Our approach to this undertaking and the lessons learned may be valuable for experts undertaking similar projects for patients with chronic diseases.

Background and aims: Perianal Crohn’s disease (pCD) is a debilitating condition with a prevalence of approximately 20% in patients within 10 years of diagnosis of CD. The condition significantly impacts patient quality of life, and there remain a number of unmet needs relating to its optimal management. A global Priority Setting Partnership (PSP) was established to identify the top 10 research priorities for pCD. Methods: The PSP followed standard James Lind Alliance (JLA) methodology. An initial survey was circulated to gather unanswered research questions from key stakeholders. From these responses, a longlist of summary questions was formed. These questions were ranked by stakeholders in a second prioritization survey. The highest ranking 19 questions were taken into the final workshop, where a panel of people with lived or professional experience of pCD identified the top 10 research priorities. Results: Over 1200 individual research questions were submitted by over 400 respondents, from over 30 countries. From the 51 summary questions that were developed from these responses, the top 10 were identified in the final workshop. These included identifying the optimal combined treatment strategy across the full spectrum of pCD, reducing the impact on quality of life, improving timely diagnosis of pCD, identifying a biological classification of pCD, and understanding and managing the impacts on sexual function, intimacy, and relationships. Conclusions: This global PSP represents a major step towards stakeholder-driven and focused research in pCD. The research priorities provide a roadmap for researchers, funders and policy-makers to align future research with patient and clinician needs to improve outcomes.

INTRODUCTION: Owing to the therapeutic ceiling associated with inflammatory bowel disease (IBD) therapies, some patients may require 2 advanced therapeutic agents, known as advanced combination treatment (ACT) to control disease or treat associated extraintestinal manifestations (EIMs). METHODS: We included adult patients with IBD from 9 Canadian centers treated with either 2 biological therapies, a biological plus an oral small molecule, or 2 small molecules. Indications for ACT were the following: (i) refractory IBD, (ii) uncontrolled immune mediated diseases, and (iii) uncontrolled EIMs. Primary outcomes were cumulative rates of clinical and endoscopic response and remission at 6 and 12 months. Secondary outcomes included serious adverse events and infections. Cox-proportional hazard analyses identified independent predictors of treatment effectiveness. RESULTS: We included 105 IBD patients (76 Crohn's disease, 29 ulcerative colitis) with median age 35 years (Interquartile Range 35.4–40.8). At baseline, 39% had perianal involvement, 58% had failed at least 3 advanced therapies, and 40% had previous surgery. The primary reason for ACT was refractory IBD (63.8%), with the add-on approach used in 97.1% cases. The most frequent combination was antitumor necrosis factor + anti-integrin. At 12 months, cumulative rates of clinical and endoscopic response were 60.0% and 32.4%, respectively, and remission rates were 29.5% and 28.6%. Perianal disease was associated with reduced clinical remission (hazard ratio [HR] = 0.33, 95% confidence interval [CI]: 0.17–0.65, P = 0.001) and endoscopic response (HR = 0.42, 95% CI: 0.12–0.50, P = 0.001). Longer disease duration (HR = 0.96, 95% CI: 0.92–0.99, P = 0.035) and baseline steroid use (HR = 0.39, P = 0.006) was associated with reduced clinical remission. Serious adverse events and infections occurred in 12.4% and 7.6% of patients, respectively. DISCUSSION: ACT was effective in achieving clinical and endoscopic outcomes in patients with refractory IBD or concomitant immune-mediated diseases/EIMs, with favorable safety profile.

Background: Risk factors for venous thromboembolism (VTE) and their relative magnitudes across different phases of care in inflammatory bowel disease (IBD) are poorly understood. Therefore, we performed a systematic review to identify risk factors for VTE in patients with IBD during the hospitalized, post-operative, post-discharge, and ambulatory phases of care. Methods: MEDLINE, EMBASE, and Cochrane CENTRAL were systematically searched from inception through to April 2024 without language restriction. We included studies that reported risk factors for VTE among adults with IBD. Summary estimates with 95% confidence intervals (CIs) were calculated for individual risk factors overall and stratified by phase of care using random effects models. Results: A total of 123 studies with over 23 510 969 patients were analyzed. We identified 48 variables for meta-analysis overall and 27 were significantly associated with VTE. The strongest risk factors were prior VTE (odds ratio [OR], 4.44; 95% CI, 2.63-7.49), surgical complications (OR, 3.06; 95% CI, 2.48-3.77), urgent surgery (OR, 2.33; 95% CI, 1.62-3.35), blood transfusions (OR, 2.68; 95% CI, 1.17-6.12), hypoalbuminemia (OR, 2.25; 95% CI, 1.93-2.62), and total parenteral nutrition (OR, 2.21; 95% CI, 1.85-2.64). Corticosteroids (OR, 1.60; 95% CI, 1.46-1.76) but not anti-tumor necrosis factor therapy (OR, 0.66; 95% CI, 0.46-0.97) were associated with an increased risk of VTE. No major differences were observed for most variables between hospitalized, post-operative, and post-discharge settings. Conclusions: We identified multiple risk factors associated with VTE across different phases of care. This work will help in the development of future predictive models to guide thromboprophylaxis in IBD.

Background and Aims: We aimed to assess the impact of setons on perianal fistula outcomes in patients with perianal fistulising Crohn's disease (PFCD) treated with anti‐TNF therapy.Methods: We included patients treated with their first anti‐TNF therapy for PFCD after undergoing a pelvic MRI between 2005 and 2022 from 6 North American centres. Our exposure was one or more setons at the time of anti‐TNF therapy. Our primary outcome was major adverse fistula outcome (MAFO), a composite of repeat local surgical intervention, hospitalisation, or faecal diversion for PFCD, and our secondary outcome was fistula remission defined clinically. We used 1:1 cardinality matching and propensity score weighting to control for fistula severity based on centrally read MRIs, luminal characteristics, and concomitant therapies.Results: Our analysis included 221 patients: 81 with setons and 140 without setons. After cardinality matching, our cohorts were balanced (standardised difference < 0.1 for all covariates). Patients with setons had similar rates of MAFO (HR 1.23; 95% CI, 0.68–2.21) and fistula remission at 6 months (OR, 0.81; 95% CI, 0.41–1.59) and 12 months (OR, 0.63; 95% CI, 0.31–1.27) compared to patients without setons. Our results remained stable when analysed by propensity score weighting and in a sensitivity analysis of patients who underwent an exam under anaesthesia. In patients with abscesses, there were lower rates of MAFO (HR, 0.49; 95% CI, 0.19–1.25) but not statistically significant in patients with setons.Conclusions: In this multicentre, setons were not associated with improved fistula outcomes. Future prospective controlled studies are warranted.

Background and Aims: Over 10% of patients with Crohn’s disease require permanent ileostomy. We aimed to summarize the existing data on diagnosis, definitions of recurrence, and management of Crohn’s disease patients with permanent ileostomy. Methods: MEDLINE, Embase, and CENTRAL databases were searched from inception to February 6, 2024. Randomized controlled trials, cohort and cross-sectional studies, and case series of more than 5 patients reporting on postoperative recurrence or the need for surgery in patients with Crohn’s disease and permanent ileostomy were included. Search results were independently screened, and full text of all titles meeting eligibility criteria was obtained. Outcomes of interest included diagnostic techniques, recurrence definitions, and management approaches. We estimated pooled rates (with 95% confidence interval [CI]) of recurrence. Results: Thirty cohort studies including 2055 Crohn’s patients with permanent ileostomy were included (53% female, median age at the time of ileostomy creation 32 years, the most common reason for ileostomy was refractory disease). The postoperative recurrence rate was 27% (95% CI, 21.3–33.3, 26 studies, 451/1805 patients). Modalities for diagnosis of Crohn’s disease recurrence were symptoms (15 studies), endoscopy (4 studies), histology from endoscopic biopsies (2 studies), imaging (5 studies), and surgery (22 studies). The reported definitions of recurrence for each modality were heterogeneous. Conclusions: There is a lack of standardized monitoring tools and criteria for diagnosing recurrence in patients with Crohn’s disease and permanent ileostomy. The results of this systematic review will form the basis of a global expert recommendation exercise focused on developing management standards and trial endpoints for this condition.

Background: There are limited tools to measure the burden of disease and effectiveness of medical/surgical interventions in patients with cryptoglandular fistulas. The aim of this study was to explore concepts that are relevant and important to patients with complex cryptoglandular fistulas (CCF) and to develop a patient-centred, disease-specific, patient-reported outcome measure (PROM) to assess symptom burden and impacts of CCF. Methods: A targeted literature review was conducted, followed by one-to-one telephone interviews with five colorectal surgeons (USA, n = 3; UK, n = 1; Spain, n = 1) and 20 US adult patients with CCF to inform the development of a conceptual model and a CCF-specific PROM. The targeted literature review informed the development of the preliminary conceptual model and identified a PROM in the literature that was used as a reference to generate the draft CCF-specific PROM. The colorectal surgeon interviews provided insights on the experience of patients with CCF to refine the conceptual model, formulate probing questions for use in patient interviews, and to develop the draft CCF-specific PROM. Patients’ descriptions of their experiences with symptoms and the impacts on their lives and evaluation of the draft CCF-specific PROM in concept elicitation and cognitive interviews were used to develop the final conceptual model and final CCF-specific PROM. Results: Ten symptoms (odour, pain during bowel movement, abscess, post-operative pain, discharge/drainage/leakage, anal/perianal pain, inflammation/swelling, skin irritation, bleeding and itchiness) and 11 impacts (discomfort, inability to exercise, embarrassment, difficulty sitting, worry about disease, adapted life to maintain hygiene, negatively impacted social life/isolation, inability to perform daily activities, reduced interest in sex, negatively impacted intimate relationships and negatively impacted mood) were reported as most salient by patients. The patient experience, clinician perspective, and literature review provided input to item generation. Evaluation of relevance and patient understanding through cognitive interviews with patients provided evidence for the content validity of the new patient-reported outcome measure: the 20-item Complex Cryptoglandular Fistula Questionnaire^™ (CCFQ-20^™). Conclusion: The CCFQ-20^™ is a new clinician-guided, patient-validated, disease-specific patient-reported outcome measure that measures disease impact and quality of life in patients with CCF.

Background The risk of metachronous advanced neoplasia after diagnosing serrated polyps in patients with IBD is poorly understood. Methods A retrospective multicenter cohort study was conducted between 2010 and 2019 at three tertiary centers in Montreal, Canada. From pathology databases, we identified 1587 consecutive patients with serrated polyps (sessile serrated lesion, traditional serrated adenoma, or serrated epithelial change). We included patients aged 45–74 and excluded patients with polyposis, colorectal cancer, or no follow-up. The primary outcome was the risk of metachronous advanced neoplasia (advanced adenoma, advanced serrated lesion, or colorectal cancer) after index serrated polyp, comparing patients with and without IBD. Results 477 patients with serrated polyps were eligible (mean age 61 years): 37 with IBD, totaling 45 serrated polyps and 440 without IBD, totaling 586 serrated polyps. The median follow-up was 3.4 years. There was no difference in metachronous advanced neoplasia (HR 0.77, 95% CI 0.32–1.84), metachronous advanced adenoma (HR 0.54, 95% CI 0.11–2.67), and metachronous advanced serrated lesion (HR 0.76, 95% CI 0.26–2.18) risk. When comparing serrated polyps in mucosa involved or uninvolved with IBD, both groups had similar intervals from IBD to serrated polyp diagnosis (p > 0.05), maximal therapies (p > 0.05), mucosal inflammation, inflammatory markers, and fecal calprotectin (p > 0.05). Conclusion The risk of metachronous advanced neoplasia after serrated polyp detection was similar in patients with and without IBD. Serrated polyps in IBD occurred independently of inflammation. This helps inform surveillance intervals for patients with IBD diagnosed with serrated polyps. Graphical Abstract

The optimal treatment of perianal fistulizing Crohn’s disease [PFCD] is unknown. We performed a systematic review with meta-analysis to compare combined surgical intervention and anti-tumour necrosis factor [anti-TNF] therapy [combined therapy] vs either therapy alone. MEDLINE, EMBASE, and Cochrane databases were searched systematically up to end December 2023. Surgical intervention was defined as an exam under anaesthesia ± setons. We calculated weighted risk ratios [RRs] with 95% confidence intervals [CIs] for our co-primary outcomes: fistula response and healing, defined clinically as a reduction in fistula drainage or number of draining fistulas and fistula closure respectively. Thirteen studies were analysed: 515 patients treated with combined therapy, 330 patients with surgical intervention, and 406 patients with anti-TNF therapy with follow-up between 10 weeks and 3 years. Fistula response [RR 1.10; 95% CI 0.93–1.30, p = 0.28] and healing [RR 1.06; 95% CI 0.86–1.31, p = 0.58] was not significantly different when comparing combined therapy with anti-TNF therapy alone. In contrast, combined therapy was associated with significantly higher rates of fistula response [RR 1.25; 95% CI 1.10–1.41, p < 0.001] and healing [RR 1.17; 95% CI 1.00–1.36, p = 0.05] compared with surgical intervention alone. Our results remained stable when limiting to studies that assessed outcomes within 1 year and studies where <10% of patients underwent fistula closure procedures. Combined surgery and anti-TNF therapy was not associated with improved PFCD outcomes compared with anti-TNF therapy alone. Due to an inability to control for confounding and small study sizes, future, controlled trials are warranted to confirm these findings.

Background: There are high rates of computed tomography (CT) utilization in the emergency department (ED) for patients with inflammatory bowel disease (IBD), despite guidelines recommending judicious use. We performed a national survey to better understand perceptions and practice patterns of Canadian physicians related to CT imaging in the ED. Methods: Our survey was developed by a multistep iterative process with input from key stakeholders between 2021 and 2022. It evaluated Canadian gastroenterologists’, surgeons’, and emergency physicians’ (1) perceived rates of IBD findings detected by CT, (2) likelihood of performing CT for specific presentations and (3) comfort in diagnosing IBD phenotypes/complications without CT. Results: A total of 208 physicians responded to our survey: median age 44 years (IQR, 37–50), 63% male, 68% academic, 44% emergency physicians, 39% gastroenterologists, and 17% surgeons. Compared with emergency physicians and surgeons, gastroenterologists more often perceived that CT would detect inflammation alone and less often IBD complications. Based on established rates in the literature, 13 (16%) gastroenterologists, 33 (40%) emergency physicians, and 21 (60%) surgeons overestimated the rates of at least one IBD complication. Although most physicians were more comfortable diagnosing inflammation compared to IBD complications without CT, gastroenterologists were significantly less likely to recommend CT imaging for non-obstructive/penetrating presentations compared with emergency physicians and surgeons with results that varied by IBD subtype. Conclusion: This national survey demonstrates differences in physician perceptions and practices regarding CT utilization in the ED and can be used as a framework for educational initiatives regarding appropriate usage of this modality.