Gilaad G Kaplan’s research while affiliated with University of Calgary and other places

During the twentieth century, inflammatory bowel disease (IBD) was considered a disease of early industrialized regions in North America, Europe and Oceania¹. At the turn of the twenty-first century, IBD incidence increased in newly industrialized and emerging regions in Africa, Asia and Latin America, while the prevalence in early industrialized regions continued to grow steadily2, 3–4. Changes in the incidence and prevalence denote the evolution of IBD across four epidemiologic stages: stage 1 (emergence), characterized by low incidence and prevalence; stage 2 (acceleration in incidence), marked by rapidly rising incidence and low prevalence; and stage 3 (compounding prevalence), where the incidence decelerates, plateaus or declines while the prevalence steadily increases. A fourth stage (prevalence equilibrium) has been proposed in which the prevalence slope plateaus due to demographic shifts in an ageing IBD population, but it has not yet been evidenced. To date, these stages have remained theoretical, lacking specific numerical indicators to define transition points. Here, using real-world data from 522 population-based studies encompassing 82 global regions and spanning more than a century (1920–2024), we show spatiotemporal transitions across stages 1–3 and model stage 4 progression. Understanding the evolution of IBD across epidemiologic stages enables healthcare systems to better anticipate the future worldwide burden of IBD.

The pathogenesis of inflammatory bowel disease (IBD) involves a complex interplay between genetic, environmental, and microbial factors. Many of these environmental determinants are modifiable, offering opportunities to prevent disease or delay its onset. Advances in the study of preclinical IBD cohorts offer the potential to identify biomarkers that predict individuals at high risk of developing IBD, enabling targeted environmental interventions aimed at reducing IBD incidence. This review summarizes findings from 79 meta-analyses on modifiable environmental factors associated with the development of IBD. Identified risk factors include smoking, Western diets, ultra-processed foods, and early-life antibiotic use, while protective factors include breastfeeding, Mediterranean diets rich in fiber, plant-based foods, and fish, along with an active physical lifestyle. Despite the promise shown by observational data, interventional or randomized controlled studies evaluating the efficacy of modifying environmental risk factors remain limited and mostly focus on dietary intervention. This review aims to inform the design of higher-quality interventional and randomized controlled studies for disease prevention while providing actionable guidance to healthcare providers on reducing the risk of developing IBD through environmental modifications.

Background Historically, randomized controlled trials (RCTs) have been criticized for being poorly generalizable to patients with ulcerative colitis (UC) evaluated in routine care. We aimed to evaluate the proportion of patients with UC starting an advanced therapy who would be eligible to participate in phase 3 registrational UC RCTs. Methods We conducted a retrospective cohort analysis of UC patients starting vedolizumab, ustekinumab, or tofacitinib at 2 IBD clinics at the University of Calgary. Patient charts, endoscopy reports, and laboratory results were reviewed, and compared against the inclusion and exclusion criteria from 5 RCTs (GEMINI-I, UNIFI, OCTAVE, ELEVATE, and LUCENT). The proportion of patients who would have been deemed eligible versus ineligible for trial participation at the time of starting a new advanced therapy was determined. Results A total of 125 patients with UC were included: 78 (62.4%) would have been eligible for at least one of the considered RCTs. Trial-eligible patients were younger, less likely to be exposed to prior immunosuppressants, and had higher C-reactive protein and fecal calprotectin. The most common reason for trial ineligibility was having inadequate disease activity at baseline (Mayo endoscopy subscore <2 or absence of rectal bleeding). A significantly greater proportion of patients would have been eligible for LUCENT (45.6%) compared to GEMINI-I (24.8%), OCTAVE (35.2%), or ELEVATE (35.2%) (P < .01 for all comparisons). Conclusions Half of patients with UC starting advanced therapy in routine care may be eligible for participation in phase 3 RCTs. Disease activity is the primary reason for trial exclusion.

Background We aimed to examine the relationship between disease symptoms and disease phenotype in a large Canadian cohort of persons with Crohn’s disease (CD). Methods Adults (n=1515) with CD from 14 Canadian centers participated in the Mind And Gut Interactions Cohort (MAGIC) between 2018 and 2023. Disease activity was measured using the 24-item IBD Symptom Inventory-Short-Form (IBDSI-SF). We compared the symptoms commonly associated with active versus inactive disease, and explored symptoms patterns in relation to disease phenotype, based on the Montreal Classification. To assess psychological status the Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9 were used. Results The mean disease duration was 15.6±11.8 years. The 5 most common symptoms were similar for those with active disease, although at higher prevalence (89% to 98%) versus those with inactive disease (47% to 79%), and included fatigue, diarrhea, gas, bloating, and urgency. The intensity of symptoms was higher in those with active than inactive IBDSI-SF scores. The rank order and relative distribution of the symptoms and intensity of the symptoms reported were similar between those with different disease phenotypes B1, B2, and B3 and L1, L2, and L3. Persons with active IBDSI-SF had a higher prevalence of anxiety (24.6%) and depression (38.2%) versus persons with inactive IBDSI-SF (6.3% and 8%, respectively) Conclusions Individuals with CD with active and inactive disease by IBDSI, experience similar symptoms, but the prevalence of symptoms and their intensity is greater in persons with active IBDSI. Persons with inactive IBDSI report many symptoms. There was no difference in symptom reporting by disease behavior or location.

Objective: SARS-CoV-2 remains the third most common cause of death in North America. We studied the effects of methotrexate and tumor necrosis factor inhibitor (TNFi) on neutralization responses after COVID-19 vaccination in immune-mediated inflammatory disease (IMID). Methods: Prospective data and sera of adults with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), and systemic lupus (SLE) were collected at six academic centers in Alberta, Manitoba, Ontario, and Quebec between 2022 and 2023. Sera from two time points were evaluated for each subject. Neutralization studies were divided between five laboratories, and each lab’s results were analyzed separately using multivariate generalized logit models (ordinal outcomes: absent, low, medium, and high neutralization). Odds ratios (ORs) for the effects of methotrexate and TNFi were adjusted for demographics, IMID, other biologics and immunosuppressives, prednisone, COVID-19 vaccinations (number/type), and infections in the 6 months prior to sampling. The adjusted ORs for methotrexate and TNFi were then pooled in random-effects meta-analyses (separately for the ancestral strains and the Omicron BA1 and BA5 strains). Results: Of 479 individuals (958 samples), 292 (61%) were IBD, 141 (29.4%) were RA, and the remainder were PsA, SpA, and SLE. The mean age was 57 (62.2% female). For both the individual labs and the meta-analyses, the adjusted ORs suggested independent negative effects of TNFi and methotrexate on neutralization. The meta-analysis adjusted ORs for TNFi were 0.56 (95% confidence interval (CI) 0.39, 0.81) for the ancestral strain and 0.56 (95% CI 0.39, 0.81) for BA5. The meta-analysis adjusted OR for methotrexate was 0.39 (95% CI 0.19, 0.76) for BA1. Conclusions: SARS-CoV-2 neutralization in vaccinated IMID was diminished independently by TNFi and methotrexate. As SARS-CoV-2 circulation continues, ongoing vigilance regarding optimized vaccination is required.

IntroductionWe previously investigated the frequency of screening for celiac disease (CD) based on tissue transglutaminase antibody testing (tTG-IgA) and developed the first incident cohort of celiac autoimmunity in Canada. Methods Administrative data sources used in this study were population-based and covered the entire province of Alberta (~4.3M residents during study period). Various approaches to querying data were employed within a diverse team of health information managers, data analysts, clinical scientists, and gastroenterologists. This process involved a broad search for CD screening tests, thorough data inspection/cleaning, and numerous discussions to determine potential explanations for the findings. ResultsApproximately ~950,000 records for tTG-IgA were first identified. Records were then excluded due to missing/invalid patient identifiers or test results (0.8%), non-Alberta residency (0.4%), and duplicate records (1.1%). A final dataset included ~920,000 tTG-IgA tests on ~680,000 unique patients, which was also validated through a separate query performed by an analyst external to the study team. A conservative approach to excluding as many potential prevalent cases of CD was applied given a robust algorithm for CD has not yet been established in Canada. The final rate of celiac autoimmunity (34 per 100,000) offered further face validity based on prior estimates of diagnosed CD in Alberta and other countries reporting on celiac autoimmunity. Conclusion When developing a novel case definition or investigating unfamiliar outcomes using routinely collected data, collaboration across several disciplines is highly recommended. Certain stages of the project may require additional scrutiny and discussion to ensure findings are valid and reliable.

We were tasked by Canada’s COVID-19 Immunity Task Force to describe severe adverse events (SAEs) associated with emergency department (ED) visits and/or hospitalizations in individuals with immune-mediated inflammatory diseases (IMIDs). At eight Canadian centres, data were collected from adults with rheumatoid arthritis (RA), axial spondyloarthritis (AxS), systemic lupus (SLE), psoriatic arthritis (PsA), and inflammatory bowel disease (IBD). We administered questionnaires, analyzing SAEs experienced within 31 days following SARS-CoV-2 vaccination. About two-thirds (63%) of 1556 participants were female; the mean age was 52.5 years. The BNT162b2 (Pfizer) vaccine was the most common, with mRNA-1273 (Moderna) being second. A total of 49% of participants had IBD, 27.4% had RA, 14.3% had PsA, 5.3% had SpA, and 4% had SLE. Twelve (0.77% of 1556 participants) SAEs leading to an ED visit or hospitalization were self-reported, occurring in 11 participants. SAEs included six (0.39% of 1556 participants) ED visits (including one due to Bell’s Palsy 31 days after first vaccination) and six (0.39% of 1556 participants) hospitalizations (including one due to Guillain-Barré syndrome 15 days after the first vaccination). Two SAEs included pericarditis, one involved SLE (considered a serious disease flare), and one involved RA. Thus, in the 31 days after SARS-CoV-2 vaccination in our IMID sample, very few serious adverse events occurred. As SARS-CoV2 continues to be a common cause of death, our findings may help optimize vaccination acceptance.

Objective: SARS-CoV-2 remains the third most common cause of death in North America. We studied methotrexate and tumor necrosis factor inhibitor (TNFi) effects on neutralization responses post-COVID vaccination, in immune-mediated inflammatory disease(IMID). Methods: Prospective data and sera on adults with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA) and systemic lupus (SLE) were collected at 6 academic centres in Alberta, Manitoba, Ontario, and Quebec between 2022-2023. Sera from two time points were evaluated for each subject. Neutralization studies were divided between 5 laboratories, and each lab’s results analyzed separately using multivariate generalized logit models (ordinal outcomes: absent, low, medium, and high neutralization). Odds ratios (ORs) for methotrexate and TNFi effects were adjusted for demographics, IMID, other biologics and immunosuppressives, prednisone, COVID vaccinations (number/type), and infections in the 6 months prior to sample. Adjusted ORs for methotrexate and TNFi were then pooled in random-effects meta-analyses (separately for ancestral, and Omicron BA1 and BA5 strains). Results: Of 479 individuals (958 samples), 292 (61%) were IBD, 141 (29.4%) RA, and the remainder PsA, SpA and SLE. Mean age was 57 (62.2 % female). For both individual labs and the meta-analyses, adjusted ORs suggested independent negative effects of TNFi and methotrexate on neutralization. The meta-analysis adjusted ORs for TNFi were 0.56 (95% confidence interval, CI 0.39, 0.81) for the ancestral strain and 0.56 (95% CI 0.39, 0.81) for BA5. The meta-analysis adjusted OR for methotrexate was 0.39 (95% CI 0.19, 0.76) for BA1. Conclusions: SARS-CoV-2 neutralization in vaccinated IMID was diminished independently by TNFi and methotrexate. As SARS-CoV-2 circulation continues, ongoing vigilance regarding optimized vaccination is required.