Risk of venous thromboembolism in patients with rheumatoid arthritis: initiating disease-modifying antirheumatic drugs

Abstract

Objectives: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Disease-modifying antirheumatic drugs; Rheumatoid arthritis; Venous thromboembolism.

Figure 1. Cohort selection flow

Our final study cohort included a total of 39,647 treatment episodes: 5,920 with bDMARDs, 17614 with methotrexate and 16,113 with nbDMARDs. RA: rheumatoid arthritis, DMARD: disease-modifying antirheumatic drug, bDMARD: biologic DMARD, nbDMARD: non-biologic DMARD

Figure 2. Duration of DMARD treatment and the risk of venous thromboembolism: Propensity score decile-stratified analysis

bDMARD: biologic DMARD, nbDMARD: non-biologic DMARD, HR: hazard ratio, CI: confidence interval Propensity score models included age, sex, comorbidities such as diabetes, obesity, chronic kidney disease, heart failure, cardiovascular disease, extremity fracture and surgeries, medications including oral contraceptives, steroids, and anti-platelet drugs, and health care utilization factors (listed in Table 1) and index year.