Risk of incident cardiovascular events with disease-modifying anti-rheumatic drugs among adults with rheumatoid arthritis: a nested case-control study

Objective This study examined the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). Method This nested case-control study used the MarketScan database (2012-2014), involving adult RA patients (aged >= 18 years) initiating either a conventional synthetic (cs) DMARD, biologic DMARD, or targeted synthetic (ts) DMARD between January 1, 2013 and December 31, 2014 (cohort entry) and had no CVD history. Cases were individuals with incident CVD identified using diagnosis codes or procedure codes from medical claims. For each case, 10 age- and sex-matched controls were selected using the incident density sampling with replacement. Prescriptions of DMARDs were measured 90 days before the event date. Conditional logistic regression examined the association of risk of CVD with DMARDs in combination treatment or individual use, with reference to methotrexate (MTX) monotherapy, adjusting for baseline confounders. Subgroup analyses were performed separately in DMARD combination therapy users or individual DMARD users, respectively. Results In total, 270 cases of incident CVD and 2700 controls were included (mean [standard deviation (SD)] age: 54 [1]; 75.6% women). The commonly prescribed DMARD therapies were csDMARD monotherapy (n = 795, 27.04%), followed by tumor necrosis factor inhibitors (TNFi) monotherapy (n = 367, 12.48%), and TNFi in combination with MTX (n = 314, 10.68%). Compared with MTX monotherapy, overall use of DMARD agents was not associated with the differential risk of CVD, including various types of DMARD combination regimens. The findings were similar across subgroup analyses. Conclusions The study found no differential risk of CVD with DMARDs in combination therapy or monotherapy compared to MTX monotherapy in patients with RA.

Automated summary

This study aimed to investigate the risk of cardiovascular disease (CVD) associated with the use of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). The study used the MarketScan database to analyze data from adult RA patients who initiated DMARD treatment between January 1, 2013 and December 31, 2014 and had no prior history of CVD. The findings showed that there was no differential risk of CVD with the use of DMARDs in combination therapy or monotherapy compared to methotrexate monotherapy in patients with RA.