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Abstract
Objectives: To determine whether a combination of anti-rheumatic drugs is associated with the risk of coronary artery diseases (CAD) in incident rheumatoid arthritis (RA) patients.
Methods: This population-based cohort study used administrative data to identify 6260 newly-diagnosed patients with RA (age ≥20 years) as the study group. The study end-point was occurrence of CAD according to the ICD-9-CM codes. Exposure to different combinations of drugs and the risk of CAD was assessed. These included different combinatiosn of celecoxib (Cx), hydroxychloroquine (HCQ), methotrexate (MTX), and sulfasalazine (SSZ). Patients who never used Cx, HCQ, MTX, or SSZ were used as a reference group. A Cox proportional hazards model was used to estimate the hazard ratio (HR) of disease after controlling for demographic and other co-morbidities. When the proportionality assumption was violated, the spline curve of the Scaled Schoenfeld residuals was fitted to demonstrate the estimated effect on CAD over time for drug usage.
Results: Among RA patients, the adjusted HR (95% confidence interval) of CAD for “Cx only”, “Cx and HCQ ever”, and “Cx, HCQ, MTX, and SSZ ever”, were 0.29 (0.19–0.44), 0.46 (0.24–0.88), and 0.42 (0.24– 0.75), respectively, during the first period of 0–3, 4, or 7 years. However, they became 1.04 (0.78–1.38), 1.16 (0.62–2.19), and 0.59 (0.32–1.08), respectively, during the second time period of 3, 4, or 7–10 years. The adjusted HR (95% CI) of CAD for “Cx, MTX, and SSZ ever” remains constant at 0.12 (0.02–0.89).
Conclusions: Celecoxib-DMARDs drug combinations were associated with reduced CAD risk on incident RA patients, and some of them exhibited the time-varying drug effect.
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Declaration of funding
This work was supported by the Chung Shan Medical University grant number CSMU-INT-104-04.
Declaration of financial/other relationships
All of the authors declare that they have no competing interests to disclose. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Acknowledgments
We thank the members of the Bureau of National Health Insurance, Department of Health, and the National Health Research Institutes for providing and managing, respectively, the National Health Insurance Research Database.
Ethics statement
This study was exempt from full review by the Institutional Review Board of the Chung Shan Medical University in Taiwan (CSMUH CS15134) because the LHID consists of de-identified secondary data released to the public for research purposes. This study did not have written informed consent. All patient records/information was anonymized and de-identified prior to analysis.