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Rheumatoid arthritis (RA) patients treated with tofacitinib (Xeljanz) and tocilizumab (Actemra) have notable changes in serum lipids compared with placebo-treated patients, according to a Spanish meta-analysis.

Compared with placebo-treated patients, those who received tocilizumab were more likely to have hypercholesterolemia (odds ratio 4.64, 95% CI 2.71-7.95, P<0.001). They were also more likely to have increased levels of high-density lipoprotein (HDL) cholesterol (OR 2.25, 95% CI 1.14-4.44, P=0.020), as well as increased levels of low-density lipoprotein (LDL) cholesterol (OR 4.80, 95% CI 3.27-7.05, P<0.001).

Among patients treated with tofacitinib, either 5 mg or 10 mg twice daily, the mean percentage of increases in HDL and LDL were also higher than in the trials' comparator groups, according to the report in the January 2015 issue of .

This effect was not observed in patients treated with tumor necrosis factor (TNF) antagonists. Limiting the study's results was the absence of lipid data for patients treated with rituximab, abatacept, or other biologics, or for patients with spondyloarthritis (SpA).

"Whether these changes pertain to the control of inflammation or to the mechanism of action of biologic agents or tofacitinib remains undetermined," wrote researchers led by Alejandro Souto, MD, of the in Spain.

While the biggest cause of death in RA and SpA is cardiovascular (CV) disease, the augmented risk of CV events and death related to accelerated atherosclerosis is not explained by traditional CV risk factors alone. Recently, systemic inflammation, as reflected by high levels of C-reactive protein and an elevated erythrocyte sedimentation rate, has been identified as a new independent risk factor.

The net effect on CV risk of improving the inflammatory burden with Janus kinase inhibitors (i.e., tofacitinib) and interleukin-6 antagonists (tocilizumab) but increasing cholesterol level is an emerging concern, the authors noted. In contrast, TNF antagonists and methotrexate appear to have positive effects on the rate of CV events.

Identifying 4,527 studies, the researchers reviewed 20 eligible articles and five documents on randomized, controlled trials (RCTs) in RA. Eligible studies included 12 RCTs of TNF antagonists (infliximab, adalimumab, golimumab), seven RCTs of tofacitinib, and six RCTS of tocilizumab. The investigators' initial objective was to assess changes in the percentage of treated RA and SpA patients with abnormal lipid values or changes in the mean percentage of increase in cholesterol and triglyceride levels.

Three RCTs of TNF inhibition reported a nonsignificant increase in the percentage of patients with hypercholesterolemia (total cholesterol >240mg/dL; OR 1.54, 95% CI 0.90-2.66, P=0.119).

A comparison across different inflammatory diseases by treatment with different biologic agents may provide important information on the link between inflammatory burden, lipid profiles, and CV events, the investigators said.

And while only tofacitinib and tocilizumab produced significant changes in the lipid profiles of RA patients, the long-term consequences of CV disease in this population need to be assessed. "Meanwhile, adequate and earlier control of disease activity and systemic inflammation may perhaps improve the risk of cardiovascular disease," they concluded.

From the American Heart Association:

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