Elevated Venous Thromboembolism Risk Associated With DMARD Switching in RA

Venous thromboembolism blood clot.
Venous thromboembolism blood clot.
Researchers found data that showed there is an elevated risk for venous thromboembolism when switching patients with rheumatoid arthritis from biologic or targeted synthetic disease-modifying antirheumatic drug treatment.

Biologic/targeted synthetic disease-modifying antirheumatic drug (b/ts DMARD) switching is associated with a higher risk of venous thromboembolism (VTE), compared with conventional synthetic DMARD (csDMARD) users and first b/ts DMARD users, according to research published in RMD Open. Disease switching may, per investigators, be a proxy for higher disease severity or poorly controlled rheumatoid arthritis (RA).

Researchers sought to assess the incidence rates of VTE in patients with RA based on the type of DMARD treatment being received or DMARD switching status. Data from a US claims database, including anonymous longitudinal data for patients insured by United HealthCare since 2000, were used for the review.

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The included study population had at least 2 RA diagnoses from medical claims at least ≥7 days apart between 2007 and 2017, received at least 1 systemic DMARD following the first RA diagnosis, and had at least 1 year of continuous health plan enrollment before the index DMARD treatment was administered. Three patient cohorts — with some overlap — were identified: biologic/targeted synthetic DMARD switchers (b/tsDMARD), first b/ts DMARD users, and conventional synthetic DMARD users (csDMARD) (n=17,726, 37,993, and 92,509, respectively). Each cohort had an average enrollment period of 4 years.

In total, 16% of csDMARD users became first b/tsDMARD users, and 25.7% of first b/tsDMARD users became b/tsDMARD switchers. Across all 3 groups, the most common comorbidities included hypertension and hyperlipidemia, followed by diabetes, chronic obstructive pulmonary disease, asthma, depression, and myocardial infarction or stroke, among others.

Overall, the crude incidence rate of VTE was 0.79 (95% CI, 0.75-0.83) per 100 patient-years. The incidence rate among those who did not use anticoagulants in the 1 year prior to the index date was 0.62 (95% CI, 0.58-0.66) per 100 patient-years. A stratified analysis found that increased VTE risk was associated with b/ts DMARD switching, being a man, increasing age, white and African American race, behavioral factors, and medication history including anticoagulant and corticosteroid use.

In b/tsDMARD switchers, the age- and sex-standardized VTE incidence rate was 0.86 (95% CI, 0.70-1.03) per 100 patient-years, which was higher than the incidence rate in first b/ts DMARD and csDMARD users (0.60 and 0.58, respectively). After stratifying by history of myocardial infarction or stroke, the age- and sex-standardized VTE incidence rate among those without myocardial infarction or stroke was 0.79, 0.53, and 0.51 in b/tsDMARD switchers, first b/tsDMARD users, and csDMARD users, respectively.

After adjusting for age, sex, and race, investigators found that the VTE risk among b/tsDMARD switchers was 50% higher than the risk for csDMARD users and 35% higher than first b/tsDMARD users. Adjusted hazard ratios were similar after adjusting for additional variables including serious infection, hypertension, hospitalizations, chronic obstructive pulmonary disease, chronic kidney disease, myocardial infarction, and stroke. Sensitivity analyses demonstrated that the crude incidence rate for VTE was 0.96 (95% CI, 0.78-1.16) per 100 person-years for second b/tsDMARD switchers and 0.87 (95% CI, 0.74-1.02) per 100 person-years for first b/tsDMARD switchers. The risk for deep vein thrombosis and pulmonary embolism “followed similar patterns in all analyses,” per researchers.

Study limitations include the use of International Classification of Diseases diagnosis to identify VTE outcomes, the use of b/tsDMARD switchers as a proxy for inadequate treatment response, and the potential misclassification of the number of previous DMARDs of all types that were used.

“In addition to line of therapy, b/tsDMARD switching and the number of switches may be an important and independent risk factor to include moving forward in observational RA drug safety studies, particularly those using secondary data sources that lack standardized disease activity measures,” the researchers concluded.

Disclosure: This clinical trial was supported by AbbVie, Inc. Multiple study authors report affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Liang H, Danwada R, Guo D, et al. Incidence of inpatient venous thromboembolism in treated patients with rheumatoid arthritis and the association with switching biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) in the real-world setting [published online September 23, 2019].  RMD Open. doi: 10.1136/rmdopen-2019-001013