Comparative Outcomes and Safety of Vedolizumab vs Tumor Necrosis Factor Antagonists for Older Adults With Inflammatory Bowel Diseases

IMPORTANCE: Observational comparative effectiveness studies can inform the positioning of biologic therapies for older patients with inflammatory bowel disease (IBD) who are underrepresented in clinical trials. OBJECTIVE: To compare the effectiveness and safety of vedolizumab vs tumor necrosis factor (TNF) for older patients with IBD. DESIGN, SETTING, AND PARTICIPANTS: This active comparator, new-user design, comparative effectiveness study was conducted between January 1, 2005, and December 31, 2018, among 754 older patients (aged ≥50 years) with IBD from the Danish National Patient Register. The mean follow-up after treatment initiation took place at 32 to 40 weeks. Statistical analysis was performed from February 1 to April 27, 2022. INTERVENTIONS: Treatment with vedolizumab or TNF antagonists. MAIN OUTCOMES AND MEASURES: The primary effectiveness outcome was treatment failure, defined as the composite risk of IBD-related hospitalization, IBD-related surgery, or a new corticosteroid prescription more than 6 weeks after initiation of treatment with biologic therapy. Secondary effectiveness outcomes were time to each individual component of the composite effectiveness outcome. The primary safety outcome was the risk of serious infections, defined as infections requiring hospitalization. A 1:1 propensity score–matched analysis was conducted, accounting for patient-, disease-, and treatment-associated factors. RESULTS: The study compared 377 older patients with IBD with incident use of vedolizumab (202 women [53.6%]; mean [SD] age, 61.2 [8.3] years; 177 [46.9%] with Crohn disease) vs 377 patients with incident use of TNF antagonists (206 women [54.6%]; mean [SD] age, 61.3 [8.1] years; 182 [48.3%] with Crohn disease). Overall, vedolizumab was associated with an increased risk of treatment failure compared with TNF antagonists (1-year risk, 45.4% vs 34.7%; adjusted hazard ratio [HR], 1.31; 95% CI, 1.02-1.69), including higher risk of IBD-related hospitalization (1-year risk, 27.8% vs 16.3%; adjusted HR, 1.48; 95% CI, 1.03-2.15) and IBD-related major abdominal surgery (1-year risk, 21.3% vs 8.0%; adjusted HR, 2.39; 95% CI, 1.45-3.94). In subgroup analysis by IBD phenotype, among patients with Crohn disease, vedolizumab was associated with a 77% higher risk of treatment failure (adjusted HR, 1.77; 95% CI, 1.21-2.58), while no difference in risk of treatment failure was seen among patients with ulcerative colitis (adjusted HR, 1.04; 95% CI, 0.75-1.43; P = .03 for interaction). There was no significant difference in the risk of serious infections, overall (1-year risk, 8.2% vs 8.7%; adjusted HR, 1.04; 95% CI, 0.58-1.85) and by IBD phenotype. CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study of older patients with IBD, vedolizumab was associated with a higher risk of treatment failure compared with TNF antagonists, particularly among patients with Crohn disease, without offering a significant safety advantage

Development of Inflammatory Bowel Disease in HIV Patients:A Danish Cohort Study (1983-2018) With American Validation (1999-2018)

BACKGROUND AND AIMS: Human immunodeficiency virus (HIV) infection is associated with several immune-mediated disorders. However, the risk of inflammatory bowel disease (IBD) in people living with HIV (PLWH) remains unclear. We aimed to assess the risk of IBD among PLWH using a nationwide, population-based Danish cohort and to validate findings in a large American insurance-based database. METHODS: Using Danish registries (1983–2018), we identified 8995 PLWH and age- and sex-matched them to 449,750 HIV-negative individuals. Cox regression analysis was undertaken to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for IBD diagnosis. Results were stratified by sex, age, and year of HIV diagnosis. Using an American insurance-based cohort, Explorys (1999–2018), we assessed the prevalence odds ratio (OR) and 95% CI of IBD diagnosis in PLWH compared with HIV-negative individuals. RESULTS: IBD diagnosis among PLWH in Denmark was increased (HR: 2.25, 95% CI: 1.78–2.83) compared with matched HIV-negative individuals. This was seen for both Crohn’s disease (HR: 2.25, 95% CI: 1.47–3.44) and ulcerative colitis (HR: 2.24, 95% CI: 1.70–2.96) and in male (HR: 2.75, 95% CI: 2.15–3.52) but not female (HR: 0.93, 95% CI: 0.48–1.79) PLWH. Explorys analysis also showed an increased odds of IBD diagnoses among PLWH (OR: 1.41; 95% CI: 1.35–1.49). CONCLUSION: This study finds an increased risk of IBD diagnosis among PLWH in both a Danish and US cohort, highlighting a need to consider IBD in PLWH with new-onset gastrointestinal symptoms. Further research into the role of antiretroviral therapy in this relationship is required

Clinical procedures used to diagnose inflammatory bowel disease:real-world evidence from a Danish nationwide population-based study

OBJECTIVE: Although clinical guidelines exist, the diagnostic work-up for diagnosing inflammatory bowel disease (IBD) is complex and varies in clinical practice. This study used real-life data to characterise the current diagnostic procedures used to establish IBD diagnoses in a Danish nationwide setting. DESIGN: Person-level data on patients diagnosed with IBD between 1 January 2014 and 30 June 2018 were linked between Danish health registers. Information on age, sex, registration of other gastrointestinal diseases, and diagnostic procedures (endoscopies, biopsies, and imaging) performed in relation to the first IBD hospital admission was analysed for the total study population and was stratified by IBD type, sex, and age. RESULTS: The majority of the 12 871 patients with IBD included underwent endoscopy (84%), had a biopsy taken (84%), and/or underwent imaging procedures (44%). In total, 7.5% of the population (6% for Crohn’s disease and 8% for ulcerative colitis) were diagnosed with IBD despite not undergoing any of these diagnostic procedures. Patients with Crohn’s disease underwent more procedures than patients with ulcerative colitis (94% vs 92%, p<0.001). Children underwent slightly fewer diagnostic procedures than adults (92% vs 93%, p=0.004). Slightly more men underwent at least one procedure than women (92% vs 94%, p<0.001). CONCLUSION: For 7.5% of patients with IBD, this study did not detect any registrations of the recommended diagnostic procedures for establishing an IBD diagnosis. Further research is needed to examine whether these findings are mainly explained by limitations of the register data or also indicate shortcomings of the general approach to IBD

The Risk of Type 2 Diabetes in Patients With Inflammatory Bowel Disease After Bowel Resections:A Nationwide Cohort Study

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) are at increased risk of type 2 diabetes (T2D), but the underlying mechanisms remain elusive. We aimed to determine the impact of small and large bowel resections on the risk of developing T2D in patients with IBD. METHODS: We conducted a nationwide, prospective study of all IBD patients undergoing small bowel resection (Crohn’s disease [CD]) and large bowel resection (CD and ulcerative colitis [UC]) in Denmark (1996–2018). Each patient was matched with up to 5 patients with IBD and no history of bowel resection. We used Cox proportional hazards regression models to estimate adjusted hazard ratios (aHRs) of T2D. RESULTS: We included 2469 patients with CD and small bowel resection, 1361 patients with CD and large bowel resection, and 3787 patients with UC and large bowel resection. Small bowel resection in CD patients was associated with lower risk of T2D (aHR 0.65, 95% CI, 0.44–0.92), compared with matched patients with CD and no bowel resection. Large bowel resection in patients with CD or UC was associated with aHRs of 0.95 (95% CI, 0.67–1.31) and 1.25 (95% CI, 1.03–1.51), respectively, compared with matched patients with CD or UC and no bowel resection. CONCLUSION: Patients with CD and small bowel resection have a lower risk of T2D, whereas patients with UC and large bowel resection have a higher risk of T2D, compared with patients with IBD and no bowel resection history. The underlying mechanisms remain to be explored