Risk of Venous Thromboembolism in Patients with Rheumatoid Arthritis: Initiating Disease-Modifying Antirheumatic Drugs

Published:December 19, 2014DOI:



      Recent research suggests that rheumatoid arthritis increases the risk of venous thromboembolism. This study compared the risk of venous thromboembolism in patients with newly diagnosed rheumatoid arthritis initiating a biologic disease-modifying antirheumatic drug (DMARD) with those initiating methotrexate or a nonbiologic DMARD.


      We conducted a population-based cohort study using US insurance claims data (2001-2012). Three mutually exclusive, hierarchical DMARD groups were used: (1) a biologic DMARD with and without nonbiologic DMARDs; (2) methotrexate without a biologic DMARD; or (3) nonbiologic DMARDs without a biologic DMARD or methotrexate. We calculated the incidence rates of venous thromboembolism. Cox proportional hazard models stratified by propensity score (PS) deciles after asymmetric PS trimming were used for 3 pairwise comparisons, controlling for potential confounders at baseline.


      We identified 29,481 patients with rheumatoid arthritis with 39,647 treatment episodes. From the pairwise comparison after asymmetric PS trimming, the incidence rate of hospitalization for venous thromboembolism per 1000 person-years was 5.5 in biologic DMARD initiators versus 4.4 in nonbiologic DMARD initiators and 4.8 in biologic DMARD initiators versus 3.5 in methotrexate initiators. The PS decile-stratified hazard ratio of venous thromboembolism associated with biologic DMARDs was 1.83 (95% confidence interval [CI], 0.91-3.66) versus nonbiologic DMARDs and 1.39 (95% CI, 0.73-2.63) versus methotrexate. The hazard ratio of venous thromboembolism in biologic DMARD initiators was the highest in the first 180 days versus nonbiologic DMARD initiators (2.48; 95% CI, 1.14-5.39) or methotrexate initiators (1.80; 95% CI, 0.90-3.62).


      The absolute risk for venous thromboembolism was low in patients with newly diagnosed rheumatoid arthritis. Initiation of a biologic DMARD seems to be associated with an increased short-term risk of hospitalization for venous thromboembolism compared with initiation of a nonbiologic DMARD or methotrexate.


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