Statin therapy linked to attenuation of tocilizumab-associated lipid increase
Concomitant statin therapy was associated with an attenuation of tocilizumab (TCZ)-mediated increase in serum lipids in patients with rheumatoid arthritis (RA), according to a recent post hoc analysis of randomized clinical studies.
“Treatment with TCZ has been shown to increase lipid levels,” said the researchers, noting that RA patients have higher cardiovascular (CV) risk and lower survival than the general population. “LDL-C [low-density lipoprotein cholesterol] levels should be monitored and managed in patients with RA.”
The retrospective post hoc analysis included seven double-blind randomized controlled phase III and IV clinical trials involving a total of 4,655 patients with moderate to severe active RA who were treated with ≥1 dose of TCZ (either intravenously [IV] or subcutaneously [SC] as monotherapy, or in combination with conventional synthetic disease-modifying antirheumatic drugs [csDMARDs]). [Rheumatol Ther 2016;doi:10.1007/s40744-016-0049-8]
A proportion of patients (n=443, 9.5 percent) were already receiving concomitant statins at baseline and 5.9 percent (n=264) initiated statins during the study, while the majority of the patients (84.8 percent, n=3,948) never started on the drug during the study period.
Among patients who were receiving concomitant statin at baseline, a smaller proportion saw their LDL-C levels increased from <130 mg/dL at baseline to ≥130 mg/dL over the first 3–4 months of TCZ therapy (31.8, 24.8, and 29.8 percent for TCZ-IV, TCZ-IV plus csDMARDs, and TCZ-SC, respectively), compared with those who never used statins during the study (38.4, 36.7, and 42.4 percent for TCZ-IV, TCZ-IV plus csDMARDs, and TCZ-SC, respectively) or those who initiated statins during the study period (53.3, 73.3, and 64.7 percent for TCZ-IV, TCZ-IV plus csDMARDs, and TCZ-SC, respectively).
From 3–4 months onwards, LDL-C levels remained high in TCZ-treated patients who were also on concomitant statins at baseline or who never used statins, while LDL-C levels gradually decreased among those who started on statins during the study, indicating a trend toward normalization of high lipid levels.
Similar trends were also observed for HDL-C, total cholesterol, and triglycerides.
At 2 years, the researchers found that less than 15 percent of patients with LDL-C ≥100 mg/dL and less than 35 percent of patients with a total cholesterol:HDL-C ratio >5 were treated with statins despite the potential CV risk.
“Unfortunately, many current risk calculators may underestimate CV disease risk in patients with RA, indicating a need for an RA-specific calculator to estimate risk of CV disease,” according to the researchers, who noted that many of the CV risk calculators such as the Framingham Risk Score and the Systematic Coronary Risk Evaluation, do not account for additional RA-specific risks as they are developed for the general population.
The European League Against Rheumatism guidelines recommended that “risk-score models should be adapted for patients with RA by introducing a 1.5x multiplication factor, and this multiplication factor should be used when patients with RA meet two of the following three criteria: disease duration >10 years, rheumatoid factor or anticyclic citrullinated peptide antibody positivity, and/or presence of certain extra-articular manifestations”, the researchers added. [Ann Rheum Dis 2010;69:325-331]