Background/Purpose: Atherosclerosis is known to be accelerated in rheumatoid arthritis (RA) patients resulting in an increased cardiovascular (CV) risk. Structural damage to joints occurs aggressively within the first few years of RA diagnosis, so it is possible that development of atherosclerosis may also be rapid during the early stages of RA. Little evidence exists on the association between use of disease-modifying antirheumatic drugs (DMARDs) and the risk of CV events in early RA patients. Our study evaluated this association in this previously understudied population.

Methods: A nested case-control study was conducted using data from a large US insurance claims database (2008-2010) representing commercial and Medicare supplemental plans. The population of interest was early RA patients, which included newly diagnosed RA patients with no medical claims indicating RA in the prior year. These patients were followed up for the outcome of a composite CV event including acute myocardial infarction, unstable angina, angina pectoris, chronic heart failure, other forms of chronic heart diseases, and cerebrovascular accident. Patients with the outcome were defined as cases on their event date. Twelve age-, sex-, and cohort entry month-matched controls were selected for each case using incidence density sampling. Seven mutually exclusive exposure categories were defined hierarchically: 1) no DMARD use, 2) past use of only non-biologic DMARDs, 3) current use of only non-biologic DMARDs, 4) past use of TNF-inhibitors, 5) current use of TNF- inhibitors, 6) past use of non-TNF biologics, and 7) current use of non-TNF biologics. Any use of these DMARDs in the period of 6 months prior to the event date was defined as current use and any use preceding that period was defined as past use.  Duration of treatment was defined as a continuous variable representing cumulative days of use. Conditional logistic regression models were used to derive estimates for incidence rate ratios (IRR).

Results: Of the 15,951 RA patients of the base cohort, 466 cases of an incident CV event were identified during follow-up. Cases were matched with 5,592 controls. In our multivariate analyses adjusting for baseline factors as well as treatment history with medications, current use of TNF-inhibitors and current use of non-biologic DMARDs were found to be associated with a reduced risk of an incident CV events compared to no DMARD use (IRR 0.62 95% CI 0.40-0.98 & IRR 0.66 95% CI 0.48-0.89 respectively). Duration of use for both TNF-inhibitors and non-biologic DMARDs was found to be associated with a reduced risk of CV events in a linear manner (for each additional month of treatment, IRR 0.95 95% CI 0.90-1.00 & IRR 0.97 95% CI 0.94-1.00 respectively).

Conclusion: Treatment with TNF-inhibitors and non-biologic DMARDs may help in reducing the risk of incident CV events in patients newly diagnosed with RA compared to no treatment with DMARDs.