CARDIOVASCULAR SAFETY AND ECONOMIC IMPACT OF ADVANCED THERAPIES IN INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW, AND REAL-WORLD EVIDENCE STUDY

Abstract

Patients with chronic immune-mediated disorders (IMID), including Inflammatory Bowel Disease (IBD), face an elevated risk of cardiovascular disease and often require advanced therapies that may influence both cardiovascular safety and healthcare costs. This thesis addresses two interrelated aims to better understand these outcomes. The first aim is to conduct a systematic review and meta-analysis of the risk of major adverse cardiovascular events (MACE) associated with advanced therapies compared to conventional treatments in patients with IBD. The second aim involves a real-world, retrospective cohort study evaluating cardiovascular safety and healthcare utilization among biologic-naïve adult IBD patients treated with infliximab reference products versus biosimilars using MarketScan claims data. In the Aim 1, a comprehensive literature search and meta- analysis were conducted to synthesize existing evidence on cardiovascular risks. Indeed, the synthesized evidence from high-quality randomized controlled trials and observational studies did not demonstrate a clear protective effect of advanced therapies on MACE in IBD patients, in contrast to findings observed in other IMIDs. In the Aim 2, a rigorously designed cohort was built with advanced statistical methods applied to compare outcomes, including the incidence rate of MACE, healthcare utilization, and cost within the first year after initiated infliximab reference product or biosimilars. The real-world evidence did not support the anticipated cost savings associated with infliximab biosimilars and provided preliminary evidence suggesting a potential increased cardiovascular risk associated with infliximab biosimilars. In conclusion, these findings underscore the need for ongoing monitoring of cardiovascular risk for advanced therapies and reconsideration the cost difference between reference products and related biosimilars in optimizing IBD management.