093 Early major adverse cardiovascular events following the initiation of the anti-interleukin 12/23 antibody ustekinumab. A population-based case-time-control study

Ustekinumab, a monoclonal antibody that targets interleukin (IL)-12/23, is used to treat psoriasis, psoriatic arthritis and Crohn disease. In 2011, a meta-analysis of randomized trials alerted on a potential risk of major adverse cardiovascular events (MACE) within the first months after the initiation of anti-IL-12/23 antibodies. Our objective was to assess if ustekinumab initiation may trigger MACE. Using the French National Health Insurance database, covering 66 million subjects, we included all patients exposed to ustekinumab between 2010 and 2016, classified according to their cardiovascular risk level (high vs. low risk). We conducted a case-time-control study. We defined the ‘risk’ period as the 6 months before MACE, defined as myocardial infarctions and strokes, and the ‘reference’ period as the 6 months before the risk period. The initiation of ustekinumab was screened in both periods, enabling to assess the odds-ratio (OR) between the initiation of ustekinumab and MACE. Among the 9290 patients exposed to ustekinumab, 179 displayed MACE: 65 myocardial infarctions, 68 unstable anginas and 46 strokes. Among patients at high-level cardiovascular risk, a significant association between ustekinumab initiation and MACE occurrence was identified (OR, 4.17; 95% CI, 1.19-14.59). Conversely, no association was found in patients at low-level cardiovascular risk (OR, 0.30; 95% CI, 0.03-3.13). From real-world data, we suggest that ustekinumab initiation could trigger MACE in patients at high cardiovascular risk, in line with current immunologic models of atherosclerotic disease. These results should call for caution regarding the prescription of ustekinumab in patients at high cardiovascular risk.