Elsevier

The American Journal of Medicine

Volume 126, Issue 8, August 2013, Pages 730.e9-730.e17
The American Journal of Medicine

AJM online
Clinical research study
Cardiovascular Risk in Rheumatoid Arthritis: Comparing TNF-α Blockade with Nonbiologic DMARDs

https://doi.org/10.1016/j.amjmed.2013.02.016Get rights and content

Abstract

Background

Elevated tumor necrosis factor (TNF)-α likely contributes to the excess cardiovascular risk observed in rheumatoid arthritis. We compared the cardiovascular risk in rheumatoid arthritis patients starting a TNF-α blocking agent versus a nonbiologic disease-modifying antirheumatic drug (nbDMARD).

Methods

Subjects with rheumatoid arthritis participating in several different US insurance programs between 1998 and 2007 who received methotrexate were eligible. Those who added a TNF-α blocking agent were compared with subjects who added a nbDMARD in Cox regression models stratified by propensity score decile and adjusted for oral glucocorticoid dosage. We examined the composite cardiovascular end point of myocardial infarction, stroke, or coronary re-vascularization after 6 months.

Results

We compared 8656 new users of a nbDMARD with 11,587 new users of a TNF-α blocking agent with similar baseline covariates. Incidence rates per 100 person-years for the composite cardiovascular end point were 3.05 (95% confidence interval [CI], 2.54-3.65) for nbDMARDs and 2.52 (95% CI, 2.12-2.98) for TNF-α blocking agents. The hazard ratio (HR) for the TNF-α blocking agent compared with nbDMARD carrying the first exposure forward was 0.80 (95%, CI 0.62-1.04), while the HR for the as-treated analysis was 0.71 (95% CI, 0.52-0.97). The potential cardiovascular benefit of TNF-α blocking agents was strongest among individuals ≥65 years of age (HR 0.52; 95% CI, 0.34 -0.77; P for interaction = 0.075).

Conclusion

Among subjects with rheumatoid arthritis, TNF-α blocking agents may be associated with a reduced risk of cardiovascular events compared with an nbDMARD. Randomized controlled clinical trials should be considered to test this hypothesis.

Section snippets

Design and Study Cohort

This study was part of a larger study collaborative (SABER: The Safety Assessment of Biologic Therapy).18 The collaborative study shared limited datasets across institutions to facilitate large-scale comparative effectiveness studies, while maintaining de-identified analytic cohorts.19 The datasets that were combined include the US Medicaid Analytic Extract linked to national US Medicare data for patients with both (so-called “dual eligibles” with Medicare and Medicaid eligibility), the

Results

The study cohort was assembled from 4 databases that provided 139,611 potentially eligible rheumatoid arthritis patients (Figure 1). Among this group, 22,907 patients had used methotrexate and then added or switched to one of the agents of interest: 9964 added or switched to a nbDMARD and 12,943 to a TNF-α blocking agent. After excluding subjects with the highest and lowest 5% of propensity scores, we compared 8656 new users of a nbDMARD with 11,587 new users of a TNF-α blocking agent.

Baseline

Discussion

As greater evidence accumulates for the role of inflammation in atherosclerosis, consideration has been given to the use of immunosuppressive treatment regimens in cardiovascular disease. While statins and aspirin may reduce cardiovascular risk in part through their anti-inflammatory properties,30, 31 targeting cytokines known to be part of cardiovascular disease is an attractive therapeutic option. Because the use of potent immunosuppressive agents is common in a systemic inflammatory

Acknowledgement

This work was supported by the Agency for Healthcare Research and Quality (AHRQ) and the Food and Drug Administration (FDA) US Department of Health and Human Services (DHHS) as part of a grant (No. 1U18 HSO17919-0) administered through the AHRQ CERTs Program. The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by AHRQ, FDA, or DHHS. This work was part of a larger collaborative, the Safety Assessment of Biologic Therapy

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  • Cited by (0)

    Funding: This work was supported by the Agency for Healthcare Research and Quality (AHRQ) and the Food and Drug Administration (FDA) US Department of Health and Human Services (DHHS) as part of a grant (No. 1U18 HSO17919-0) administered through the AHRQ CERTs Program.

    Conflict of Interest: DHS has received research grants from Abbott, Amgen, and Lilly; has served in unpaid roles on 2 Pfizer trials not related to rheumatoid arthritis; has directed an educational course supported by Bristol Myers Squibb; and serves as a consultant to CORRONA. JRC has received research grants or consulted (or both) with Amgen, Abbott, BMS, Genentech/Roche, Janssen, UCB, and CORRONA. LRH serves as a consultant to CORRONA. JDL has received research grant from Centocor and served as a paid consultant to Amgen and Pfizer.

    Authorship: All authors had access to the data and a role in writing the manuscript.

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