IBD treatments and risk of major adverse cardiovascular events in older adults

Patients with inflammatory bowel disease (IBD) are at increased risk of major adverse cardiovascular events (MACE) related to chronic inflammation, endothelial dysfunction and use of certain therapeutic regimens. Given the inflammatory link, it is biologically plausible that effective control of systemic inflammation with immunomodulators or biologics could reduce the risk of cardiovascular disease as a result of the favourable effects of these medication classes on inflammatory pathways. However, existing data are mixed and it remains unclear whether different IBD treatments alter the risk of MACE.To explore this issue, U.S. researchers examined the association between the use of immunomodulators or biologics versus 5-aminosalicylic acid (5-ASA) with the risk of MACE among older patients with IBD. 5-ASA was used as the comparator in the study; it controls mild to moderate colonic inflammation and acts locally on the bowel mucosa to suppress inflammation. Immunomodulators and biologics are used to effectively control systemic inflammation in moderate to severe IBD. The comparative effectiveness study was conducted using a 15% Medicare claims sample of patients with IBD age 65 years or older. Entry to the study was defined by the first prescription of immunomodulators, biologics or 5-ASA over a nine-year period (January 2012–December 2020). Follow-up extended to the outcome, switch or discontinuation of the study drug, the study’s administrative end, or up to three years, whichever occurred first. Propensity score matching at a 1:3 ratio was used to balance demographics, comorbidities and medication use between groups. Exposures were categorized as use of immunomodulators (e.g., tacrolimus, methotrexate) or biologics (antitumour necrosis factor therapy [e.g., infliximab, adalimumab], anti-interleukin (IL) 12 and 23 therapy [e.g., guselkumab, risankizumab, ustekinumab] and anti-integrin therapy [e.g., natalizumab, vedolizumab]) compared with 5-ASA.The primary outcome was time to the first emergency department or inpatient visit caused by a MACE, defined as myocardial infarction, stroke or all-cause mortality. Hazard ratios (HRs) and 95% confidence intervals (CIs) for MACE risk with immunomodulators or biologics versus 5-ASA were estimated using Cox proportional hazards models.Key results:A total of 16,387 patients (mean age, 74.73 years; 60.18% female) were included in the analysis. In the immunomodulators versus 5-ASA cohort, the mean age was 74.05 years and 58.85% were female. In the biologics versus 5-ASA cohort, the mean age was 73.68 and 58.09% were female. Baseline comorbidities were mostly balanced between groups. Compared with 5-ASA, no statistically significant difference in the risk of MACE was seen for immunomodulators (HR, 0.84 [95%CI, 0.61–1.17]) or biologics (HR, 0.86 [95%CI, 0.59–1.24]). Although the hazard ratios were below 1, suggesting a lower risk of MACE with immunomodulators or biologics compared to 5-ASA, the differences were not statistically significant.No statistically significant differences were observed by IBD subtypes (i.e., ulcerative colitis and Crohn’s disease).In this comparative effectiveness study of older patients with IBD, no statistically significant difference in MACE risk was found between those who used immunomodulators or biologics versus 5-ASA. The authors point out that these findings provide reassurance regarding the cardiovascular safety of therapies targeting systemic inflammation in this high-risk population.Reference:Jian Q, Chaudhry NA, Du F, et al. Immunomodulators, biologics, and 5-ASA for inflammatory bowel disease and major adverse cardiovascular events in older adults. JAMA Netw Open 2026;9;(4):e269091. Published Online: April 29, 2026. (accessed May 5, 2026).

IBD treatments and risk of major adverse cardiovascular events in older adults

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