Among patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARDs), cardiovascular (CV) risk associated with abatacept and tumor necrosis factor(TNF)-α inhibitors is lower compared with conventional synthetic DMARDs (csDMARDs), according to study results published in The Journal of Rheumatology.

Systemic inflammation and traditional CV risk factors contribute to the increased CV risk among patients with RA. The aim of the current study was to investigate the comparative effects of DMARDs on CV risk in patients with RA.

The prospective cohort study included participants in FORWARD, the National Databank for Rheumatic Diseases. All subjects were 18 years of age and older and completed at least 2 semiannual questionnaires during the period from 1998 through 2017. DMARD exposure was categorized into 7 groups: (1) csDMARDS (reference) (2) TNF inhibitors (3) abatacept (4) rituximab (5) tocilizumab (6) anakinra, or (7) tofacitinib.


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The primary outcome was a composite CV event, including myocardial infarction, stroke, hospitalized heart failure and death from cardiovascular disease (CVD).

The study sample included 18,754 (mean age, 58.6 years; 79.4% women) patients with RA.

During median follow-up of 4 years, a total of 1801 composite CV events was recorded with an incidence rate of 1.78 (95% CI, 1.69-1.87) per 1000 patient-years.

Patients with RA who developed CVD were older than those who did not develop CVD (67.5 vs. 57.5 years, P <.001), had longer disease duration (mean 16.6 vs. 14.0 years, P <.001), and higher rates of diabetes (16.4% vs. 8.2%, P <.001), hypertension (42.0% vs. 31.0%, P <.001), and prior CVD (15.7% vs. 4.2%, P <.001).

Compared with csDMARDs, treatment with TNF inhibitors (hazard ratio [HR], 0.81; 95% CI, 0.71-0.93) and abatacept (HR, 0.50; 95% CI, 0.30-0.83) were associated with a decreased CV risk. No significant difference in CV risk was identified for other biological DMARDs and tofacitinib, compared with csDMARDs.  The decreased risk associated with TNF inhibitors remained significant following exclusion of patients with prior CVD, but the risk reduction associated with abatacept was no longer significant.

Of all TNF inhibitors, statistically significant CV risk reduction was identified for infliximab (HR, 0.81; 95% CI, 0.71-0.93) and etanercept (HR, 0.81; 95% CI, 0.71-0.93).

Of the csDMARDs, methotrexate use compared to non-use was associated with 18% reduction in cardiovascular risk (HR, 0.82; 95% CI, 0.74-0.90). Compared with methotrexate, TNF inhibitors and abatacept were no longer associated with a significant decrease of CV risk, other than a decreased risk for myocardial infarction associated with TNF inhibitors (HR, 0.85; 95% CI, 0.66-0.96).

In addition, higher glucocorticoid exposure was associated with increased CV risk, and this risk increased with higher dose and longer treatment duration. The protective effect of TNF inhibitors, abatacept and methotrexate abated with concomitant use of glucocorticoids.

The study had several limitations, according to the researchers, including the observational design, inclusion of prevalent and new users, potential unmeasured confounders, missing data on the control of traditional CV risk factors, relatively small number of cardiovascular events, and potential participation bias.

“Abatacept and TNFi [TNF inhibitors] were associated with decreased risk of CVD compared to csDMARDs. Minimizing glucocorticoid use and optimizing MTX [methotrexate] dose may improve CV outcomes in patients with RA,” concluded the researchers.

Disclosure: This clinical trial was supported by Pfizer. Please see the original reference for a full list of authors’ disclosures.

Reference

Ozen G, Pedro S, Michaud K. The risk of cardiovascular events associated with disease-modifying antirheumatic drugs in rheumatoid arthritis. J Rheumatol. Published online Aug 15, 2020. doi:10.3899/jrheum.200265