Older adults with inflammatory bowel disease (IBD) treated with immunomodulators or biologic therapies did not have a statistically higher risk of major adverse cardiovascular events (MACE) than those treated with 5-aminosalicylic acid (5-ASA), according to a comparative effectiveness study of Medicare beneficiaries.
Compared with 5-ASA, immunomodulator use was not associated with a statistically significant difference in MACE risk (HR, 0.84; 95% CI, 0.61-1.17), nor was biologic use (HR, 0.86; 95% CI, 0.59-1.24).
Although the analysis did not demonstrate statistically significant cardiovascular benefit with advanced therapies, the findings may provide reassurance for clinicians managing an aging IBD population with substantial baseline cardiovascular risk.
The study, published in JAMA Network Open, evaluated more than 16,000 Medicare beneficiaries aged 65 years and older with Crohn disease or ulcerative colitis who initiated treatment with immunomodulators, biologics, or 5-ASA between 2012 and 2020. According to the study, the investigators found no statistically significant differences in the risk of MACE, which is defined as myocardial infarction, stroke, or all-cause mortality, between patients receiving immunomodulators or biologics and those treated with 5-ASA.
“There was no statistically significant difference in MACE risk between those who used immunomodulators or biologics vs 5-ASA,” the authors wrote.
IBD has long been associated with an elevated risk of cardiovascular disease, a relationship believed to be driven in part by chronic systemic inflammation. At the same time, uncertainty has persisted regarding whether therapies that suppress inflammation influence cardiovascular outcomes, particularly among older adults who already carry increased cardiovascular risk because of age and comorbidities.
To address that question, the investigators analyzed a 15% national sample of Medicare fee-for-service claims. After propensity score matching to balance demographic characteristics, comorbidities, and medication use, they compared patients initiating immunomodulators with matched patients receiving 5-ASA and conducted a separate comparison of biologics versus 5-ASA. Patients were followed until a cardiovascular event, treatment discontinuation or switching, death, the end of Medicare enrollment, or up to three years.
According to the study, neither immunomodulators nor biologics were associated with a statistically significant increase in MACE compared with 5-ASA. Although the hazard ratio estimates for both treatment groups were numerically below 1, the 95% confidence intervals included 1.0, and the differences were not statistically significant.
The authors reported that the findings remained generally consistent across multiple sensitivity analyses, including intention-to-treat analyses, alternative cardiovascular outcome definitions, latent-period analyses, subgroup analyses by ulcerative colitis and Crohn disease, and methods accounting for informative censoring.
The study also examined the biological rationale for a possible cardiovascular effect of advanced therapies. According to the authors, persistent inflammatory signaling in IBD contributes to endothelial dysfunction, arterial stiffness, and atherosclerosis, raising the possibility that therapies targeting systemic inflammation could favorably influence cardiovascular health. However, the investigators emphasized that the current findings do not establish a cardiovascular benefit.
“In this comparative effectiveness study of Medicare beneficiaries with IBD, we observed no statistically significant difference in major adverse cardiovascular events (MACE) among patients treated with immunomodulators or biologics compared with 5-ASA,” corresponding author Tianze Jiao, PhD, said in an interview with GI & Hepatology News.
Dr. Jiao added that the findings “suggest that advanced therapies were not associated with an increased cardiovascular risk compared with 5-ASA, which may reassure clinicians when selecting therapies based on clinical needs and disease severity.”
The findings may reassure clinicians that immunomodulators and biologics were not associated with excess MACE risk in this older Medicare population, but the observational design means treatment decisions should still be individualized according to disease severity, comorbidities, and patient preferences.
“Clinicians should continue to individualize anti-inflammatory treatment decisions based on disease severity (e.g., biomarkers), and patient characteristics as well as preference,” Dr. Jiao said.
He added that the findings suggest advanced therapies “may even confer potential cardiovascular benefits through systemic inflammation reduction, although additional studies are needed to confirm this hypothesis.”
The investigators cautioned that several limitations should be considered when interpreting the findings. According to the study, Medicare claims data do not include biomarkers, inflammatory indices, body mass index, or other direct measures of disease activity, making residual confounding possible despite extensive adjustment. The authors also noted that the composite MACE outcome may obscure differences among its individual components and that the relatively short median follow-up may have limited the ability to detect longer-term cardiovascular effects. In addition, the authors acknowledged that unmeasured factors, including over-the-counter medication use and socioeconomic characteristics, could not be fully accounted for.
The authors said the findings offer reassurance for clinicians treating older adults with IBD.
“Although no statistically significant differences in cardiovascular risk were observed, these findings provide reassurance regarding the cardiovascular safety of therapies targeting systemic inflammation in this high-risk population,” they wrote, adding that future studies incorporating clinical and biomarker data are needed “to elucidate the mechanisms linking anti-inflammatory treatment with cardiovascular health.”
Dr. Zimmermann reported receiving grants from Bishop Parker Foundation Support, Pfizer, and the Consortium for Medical Marijuana Clinical Outcomes Research Bench outside the submitted work. No other disclosures were reported.