medwireNews: Findings from the ENTRACTE trial suggest that the risk for major adverse cardiovascular events (MACE) with tocilizumab may not be markedly greater than that with etanercept.
The study results ruled out a hazard ratio (HR) of 1.8 or more for MACE in patients with rheumatoid arthritis (RA) treated with tocilizumab, which targets the interleukin-6 receptor alpha, versus the tumor necrosis factor inhibitor etanercept.
The researchers estimate that RA patients treated with tocilizumab were about 5% more likely to experience MACE compared with those treated with etanercept. However, they caution that “the uncertainty around this estimate was wide enough that the true risk for MACE in the tocilizumab arm could have been anywhere from 43% higher to 23% lower than in the etanercept arm.”
Between August 2011 and March 2016, 3080 individuals with active seropositive RA and at least one cardiovascular risk factor were randomly allocated to one of two groups, with an average follow-up of 3.2 years. The first group received tocilizumab 8 mg/kg/month (n=1538), while the second group received etanercept 50 mg/week (n=1542).
During follow-up, 83 patients taking tocilizumab experienced MACE, consisting of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, compared with 78 of those given etanercept, yielding an HR of 1.05 and a 95% confidence interval (CI) of 0.77–0.43.
This rules out a HR of 1.8–2.0 or above for MACE in line with screening evaluations for cardiovascular safety conducted for other agents, such as antidiabetes drugs and obesity therapies, Jon Giles (Columbia University College of Physicians and Surgeons, New York, USA) and study co-authors explain in Arthritis & Rheumatology.
However, Giles and colleagues were able to rule out a HR of 1.8 or above for MACE, but they were unable to rule out “traditional inferiority margins,” as their HR of 1.43 did not fall within in the pre-specified range of 1.3-1.33.
They observed that patients treated with tocilizumab had increased levels of circulating lipids by week 4. Low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels were increased by 11.1%, 5.7%, and 13.6%, respectively, in patients treated with tocilizumab, compared with etanercept.
Giles and team point out that because “deaths from atherosclerotic events and cardiovascular disease (CVD) are higher in patients with RA than in those without, treatment-associated increased concentrations of lipids with atherogenic potential have called into question the CVD risk-to-benefit ratio of tocilizumab in RA.”
But they conclude: “Based on the findings of ENTRACTE, CVD risk on tocilizumab does not appear to be markedly increased compared with that on etanercept, at least within the first several years after therapy initiation.”
By Hannah Kitt
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