Abstract
Objective. We evaluated the associations between time-varying methotrexate (MTX) use and risk of cardiovascular events (CVE) in patients with rheumatoid arthritis (RA).
Methods. We studied an inception cohort of 23,994 patients with RA diagnosed after their 65th birthday. Multivariable Cox regression models were fit to evaluate the associations between time-varying MTX use, controlling for other risk factors, and time to CVE. Alternative models assessed the cumulative duration of MTX use over the (1) first year, (2) previous year (recent use), and (3) entire duration of followup. We also assessed whether the strength of the association varied over time.
Results. Over 115,453 patient-years (PY), 3294 (13.7%) patients experienced a CVE (28.5 events per 1000 PY; 95% CI 27.6–29.5). In the multivariable analyses, the model assessing time-varying continuous use in the most recent year yielded the best fit. Increasing recent MTX use was associated with lower CVE risks (HR 0.79 for continuous use vs no use in past 12 months, 95% CI 0.70–0.88; p < 0.0001). Greater MTX use in the first year after cohort entry was also protective (HR 0.84, 95% CI 0.72–0.96; p = 0.0048), but this effect decreased with increasing followup. In contrast, longer MTX use during the entire followup was not clearly associated with CVE risk (HR 0.98, 95% CI 0.95–1.01; p = 0.1441).
Conclusion. We observed about a 20% decrease in CVE associated with recent continuous MTX use. Greater MTX use in the first year of cohort entry also appeared to be important in the association between MTX and CVE risk.
Footnotes
This analysis was supported by the Canadian Network for Advanced Interdisciplinary Methods for comparative effectiveness research, which is funded by the Canadian Institutes of Health Research Drug Safety and Effectiveness Network (funding reference no. TD3-137716). JW was supported by fellowship awards from The Arthritis Society and the Canadian Institutes of Health Research (Banting) during the course of this work; SB holds a career award from the Fonds de la recherche en santé du Québec; MA is a James McGill Professor of Biostatistics at McGill University. This study was supported by the ICES, a nonprofit research corporation funded by the Ontario Ministry of Health and Long-Term Care. Parts of this material are based on data and/or information compiled and provided by the Canadian Institutes of Health Information (CIHI). However, the analyses, conclusions, opinions, and statements expressed in the material are those of the authors and not necessarily those of CIHI.
- Accepted for publication August 22, 2018.