Major Cardiovascular Event Risk of Advanced Therapies in Inflammatory Bowel Diseases: Systematic Review and Meta-Analysis

BackgroundPatients with chronic immune-mediated disorders (IMIDs), including inflammatory bowel disease (IBD), are at increased risk of cardiovascular disease. While advanced therapies show cardioprotective effects in other IMIDs, their impact on major adverse cardiovascular events (MACE) in IBD remains unclear. We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating MACE risk with advanced therapies in IBD. MethodsSystematic search of PubMed, Embase and Cochrane Central identified 43 high-quality studies (36 RCTs,7 observational studies) published between 2002 and 2024. Primary analyses estimated odds ratios (OR) for MACE comparing advanced therapy to placebo, with secondary analyses stratified studies by drug class and length of follow-up. ResultsPlacebo-controlled RCTs showed a nonsignificant trend toward reduced MACE risk (OR: 0.60; 95% CI: 0.24-1.51), with similar findings after continuity correction for zero-event studies (OR: 0.87; 95% CI: 0.45-1.68). Class-specific trends suggested lower MACE risk with IL-12/IL-23 inhibitors (OR: 0.35; 95% CI: 0.05-2.21), JAK inhibitors (OR: 0.57; 95% CI: 0.16-2.06), and a potential increase with anti-TNF agents (OR: 3.04; 95% CI: 0.31-29.47), though none reached statistical significance. Long-term follow-up studies showed consistent findings. Observational studies suggested lower MACE risk for anti-TNF therapies (OR: 0.29; 95% CI: 0.21-0.40), but not for IL-12/IL-23 (OR: 4.41; 95% CI: 0.49-39.28) or JAK inhibitors (OR: 1.57; 95% CI: 0.86-2.84). ConclusionAdvanced therapies did not demonstrate a clear increase or decrease in cardiovascular risk in IBD. The discrepancies between RCTs and observational studies underscore the urgent need for rigorous-designed observational research with long-term follow-up to evaluate the real-world impact of advanced therapies on MACE risk. SummaryThis study evaluated cardiovascular safety of advanced therapies in inflammatory bowel disease. Findings showed no clear signal of decreased major cardiovascular risk compared with conventional treatment, highlighting the need for continued monitoring through long-term and real-world evidence. Key MessagesO_LIWhat is already known? Patients with IBD are at increased risk of cardiovascular events, and the impact of advanced therapies on this risk remains uncertain. C_LIO_LIWhat is new here? This meta-analysis integrates data from randomized and observational studies and found no significant association between advanced therapies and MACE. C_LIO_LIHow can this study help patient care? Findings show no clear signal of decreased cardiovascular risk with advanced IBD therapies, though continued evaluation is warranted. C_LI