Tocilizumab is associated with a lower incidence of major adverse cardiovascular events in Giant Cell Arteritis

Introduction Giant cell arteritis (GCA) is associated with a markedly increased risk of major adverse cardiovascular events (MACE), driven by systemic inflammation1. Interleukin-6 (IL-6) signalling plays a central role in atherogenesis2,3, yet whether IL-6 inhibition reduces cardiovascular risk in humans remains an open question currently being investigated in the general population. Purpose To compare the risk of MACE among patients with incident GCA initiating tocilizumab versus methotrexate. Methods We conducted a nationwide observational study emulating a target trial using the French National Health Data System (SNDS). Adults hospitalised for incident GCA between 2012 and 2024 who initiated tocilizumab or methotrexate within 6 months after discharge were included. The primary outcome was first MACE (coronary event, ischaemic stroke, or death). Treatment effects were estimated using a clone–censor–weight approach with inverse probability of censoring weighting. Two-year cumulative incidences, absolute risk differences, and hazard ratios (HRs) with 95% confidence intervals (CIs) were reported. Results Among 1,667 patients (mean age 73.6±8.2 years; 69.0% women), 912 initiated tocilizumab and 755 methotrexate. At 2 years, the cumulative incidence of MACE was 7.5% (95% CI 5.6–9.4) with tocilizumab and 10.5% (95% CI 8.3–12.8) with methotrexate, corresponding to an absolute risk difference of −3.0% (95% CI −5.7 to −0.3). Tocilizumab was associated with a lower risk of MACE (HR 0.79, 95% CI 0.62–0.98). This association was driven by fewer coronary events (HR 0.59, 95% CI 0.36–0.92), with a 2-year cumulative incidence of 1.9% (95% CI 0.8–3.2) versus 3.4% (95% CI 2.1–4.9). There was no significant difference in ischaemic stroke (HR 1.07, 95% CI 0.76–1.51) or all-cause mortality (HR 0.94, 95% CI 0.68–1.27). Conclusions In this nationwide target trial emulation, IL-6 receptor blockade with tocilizumab was associated with a lower risk of MACE compared with methotrexate in GCA, primarily through a reduction in coronary events. These findings support a potential role of IL-6–mediated inflammation in atherosclerosis progression and suggest that patients with GCA represent a clinical model of inflammation-driven atherosclerosis. This work provides real-world evidence complementary to ongoing cardiovascular outcome trials of IL-6 inhibition and supports further investigation of anti-inflammatory strategies in atherosclerotic disease.Figure 1Figure 2