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AMSTERDAM -- Currently available medications for rheumatoid arthritis (RA) not only alleviate symptoms and help avert progression and joint damage, but also help limit these patients' elevated cardiovascular risks, a series of reports presented here showed.

In a special session entitled "Treatments: Friend or Foe?" at the , which is sponsored by the European League Against Rheumatism, researchers reported on the cardiovascular effects of hydroxychloroquine, methotrexate, and tocilizumab (Actemra).

"RA is associated with a marked increase in cardiovascular comorbidity and mortality, a risk that is present from the early stages of disease and which represents a complex relationship between traditional and RA-specific risk factors," explained Kasper Soeltoft, MD, PhD, of Odense University Hospital in Denmark.

Hydroxychloroquine has been used as part of combination therapy with methotrexate and sulfasalazine for RA, and has been associated with lowered risks for diabetes and dyslipidemia in these patients. The drug also has been shown to improve survival in systemic lupus erythematosus, but its potential cardiovascular benefits in RA are uncertain.

So he and his colleagues identified 29,611 incident cases of RA from 2004 to 2014 in national Danish registries, of which 5,574 were hydroxychloroquine initiators.

A total of 3,742 initiators were matched by propensity scores with a non-initiator for purposes of comparison for all-cause and cardiovascular mortality, and found significant reductions for both:

• All-cause mortality: HR 0.83 (95% CI 0.71-0.97)
• Cardiovascular mortality: HR 0.78 (95% CI 0.61-0.99)

"These results appear to support the use of hydroxychloroquine in combination with other disease-modifying anti-rheumatic drugs in RA, despite the fact that hydroxychloroquine's effects on RA disease activity itself is limited," Soeltoft concluded.

In a second study, the cardiovascular effects of methotrexate were assessed retrospectively using Medicare claims data for the years 2006 to 2015 among patients with RA who were initiating biologic therapy. "Overall, there was a 23% cardiovascular risk reduction among patients who used methotrexate in combination with a biologic," said Michael George, MD, of the University of Alabama at Birmingham.

This was out of 88,255 biologic initiations in 64,218 patients. Patients' mean age was 65 years, 84% were women, and 68% were non-Hispanic white.

The unadjusted incidence rates for cardiovascular events -- incident myocardial infarction, stroke, or fatal cardiovascular disease -- were 13.1/1,000 patient-years (95% CI 12.2-14) for those on concomitant methotrexate compared with 18.7/1,000 (95% CI 17.6-19.9) for those not using methotrexate, which was a significant difference (P=0.0189).

When the researchers looked at the individual biologics, they found hazard ratios ranging from 0.61 (95% CI 0.37-1.01) for golimumab (Simponi) to 0.97 (95% CI 0.74-1.26) for adalimumab (Humira).

A limitation of the analysis was the possibility of residual confounding.

A third study, also presented by George, demonstrated that treatment of RA with tocilizumab was not associated with elevated cardiovascular disease risk despite this agent's recognized unfavorable changes on lipid profiles.

The retrospective cohort study analyzed data from Medicare and MarketScan claims for the years 2006 to 2015 among patients who initiated biologics, with a composite outcome of myocardial infarction, stroke, or fatal cardiovascular disease.

The analysis included 88,463 RA patients and 117,493 biologic initiations. Most patients were white women, and mean ages were 65 among Medicare patients and 52 for MarketScan patients.

Those who initiated tocilizumab were more likely than patients using tumor necrosis factor inhibitors to be white and to have a history of heart failure, atrial fibrillation, and hospitalization, but were less likely to be diabetic, to use methotrexate, and to be biologics-naive.

The incidence rates for the composite endpoint among the Medicare patients ranged from 13.3/1,000 patient-years for etanercept (Enbrel) to 19.4/1,000 (95% CI 16.3-20.9) for rituximab (Rituxan).

Compared with tocilizumab, the adjusted hazard ratios for the cardiovascular endpoint were:

• Abatacept (Orencia), HR 1.03 (95% CI 0.82-1.29)
• Rituximab, HR 1.25 (95% CI 0.96-1.61)
• Etanercept, HR 1.13 (95% CI 0.84-1.52)
• Adalimumab, HR 1.33 (95% CI 0.99-1.80)
• Infliximab (Remicade), HR 1.57 (95% CI 1.21-2.05)

"There were no signs that tocilizumab was riskier from a cardiovascular standpoint than other biologics," George concluded.