Comparative Effectiveness and Cardiovascular Outcomes of Infliximab reference product and Biosimilars in Patients with Inflammatory Bowel Disease

BackgroundAnti-tumor necrosis factor (anti-TNF), particularly infliximab, have transformed inflammatory bowel disease (IBD) management, but their high cost imposes a significant economic burden. Infliximab biosimilars were introduced to reduce the unmet needs. Despite the approval of infliximab biosimilars, real-world evidence of cardiovascular safety and effectiveness of infliximab biosimilars is lacking among patients with IBD. In this trial emulation, we compared the effectiveness and cardiovascular safety between patients who initiated infliximab reference product (IFX-RP) and biosimilars (IFX-BP). MethodsUsing the Merative Marketscan Research database (2011-2023), we conducted a retrospective cohort study to emulate the target trial where biologic-naive adults were randomly assigned to initiate IFX-RP or IFX-BP. Primary outcomes included healthcare resource utilization (HRU), and incidence of major adverse cardiovascular events (MACE) over one year. Propensity score matching was applied to mimic the randomization. Both intention-to-treat and per-protocol effects were estimated. ResultsAfter matching, 850 patients (425 per group) were included. HRU was comparable between IFX-RP and IFX-BP groups across outpatient visits, hospitalizations, surgeries, and emergency visit. During follow-up, MACE events were more frequent in the IFX-BP group (9 vs. 3), with an incidence rate ratio (IRR) of 3.04 (95% CI: 0.82-11.23). Although the difference was not statistically significant, consistent directional trends were observed across analyses. Sensitivity analyses supported primary results. ConclusionOur study found comparable effectiveness between IFX-RP and IFX-BP in routine clinical care. While cardiovascular events were infrequent, the potential signal suggesting increased MACE risk associated with infliximab biosimilars warrants further investigation. Continued pharmacovigilance is essential to ensure the cardiovascular safety of biosimilars. SummaryInfliximab biosimilars, introduced to reduce the economic burden of anti-TNF therapy in IBD, demonstrated comparable real-world effectiveness to the infliximab reference product in a target trial emulation using Merative MarketScan data, while a potential signal of increased cardiovascular risk underscores the need for ongoing pharmacovigilance and further investigation. Key MessagesO_LIWhat is known? Infliximab biosimilars demonstrate comparable efficacy and safety to the reference product in IBD, but cardiovascular outcomes remain underexplored. C_LIO_LIWhat is new here? This U.S. real-world study emulating a target trial found similar effectiveness between infliximab reference and biosimilar products, with a possible trend toward increased cardiovascular risk in biosimilar users. C_LIO_LIHow can this study help patient care? Findings highlight the need for continued pharmacovigilance and cardiovascular monitoring when prescribing infliximab biosimilars to optimize safety in IBD management. C_LI