Circulation. 2026 Aug 29. doi: 10.1161/CIRCULATIONAHA.126.080365. Online ahead of print.
ABSTRACT
BACKGROUND: Giant cell arteritis is associated with increased cardiovascular risk, potentially related to systemic inflammation, vascular injury, and glucocorticoid exposure. Whether steroid-sparing therapies differentially influence cardiovascular outcomes in giant cell arteritis remains uncertain.
METHODS: We conducted a nationwide observational cohort study emulating a target trial using the French National Health Data System from January 1, 2012, to December 31, 2024. We included patients hospitalized for incident giant cell arteritis who initiated tocilizumab or methotrexate within 6 months after discharge. The primary outcome was the first major adverse cardiovascular event, defined as any coronary event, ischemic stroke, or all-cause death. Treatment effects were estimated with a clone-censor-weight approach with inverse probability of censoring weighting. We estimated 2-year cumulative incidences, absolute risk differences, and hazard ratios with 95% CIs.
RESULTS: In 1997 patients with incident giant cell arteritis (mean age, 73.1±8.3 years; 70.4% women), 1095 initiated tocilizumab and 902 initiated methotrexate within 6 months after discharge. At 2 years, the cumulative incidence of major adverse cardiovascular events was 6.4% (95% CI, 4.9%-7.9%) with tocilizumab and 10.7% (95% CI, 8.4%-12.9%) with methotrexate (risk difference, -4.3% [95% CI, -6.6% to -1.7%]). Tocilizumab initiation was associated with a lower risk of major adverse cardiovascular events (hazard ratio, 0.60 [95% CI, 0.48-0.75]), driven by fewer coronary events (hazard ratio, 0.55 [95% CI, 0.37-0.84]) and all-cause deaths (hazard ratio, 0.53 [95% CI, 0.36-0.74]). Results were consistent in sensitivity analyses using alternative grace periods, corticosteroid dose thresholds, restriction to the 2017 to 2024 period, and a per-protocol-analogous approach. Negative control outcomes did not differ meaningfully between treatment strategies.
CONCLUSIONS: In this nationwide target trial emulation of incident giant cell arteritis, initiation of tocilizumab was associated with a lower risk of major adverse cardiovascular events compared with methotrexate, primarily through a reduction in coronary events and all-cause deaths.
REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT07459335.
PMID:42667206 | DOI:10.1161/CIRCULATIONAHA.126.080365