Tocilizumab Linked to High LDL, but not Cardiovascular Risk in RA

Tocilizumab may be associated with increasing LDL cholesterol in rheumatoid arthritis patients, but a new study shows that it is not associated with increased cardiovascular risk.

Reporting in the April 28 issue of Arthritis & Rheumatology, researchers report having found no increased risk of myocardial infarction or stroke in rheumatoid arthritis patients who were switched from a different biologic or tofacitinib to tocilizumab compared to a TNFi.

Even in patients with pre-existing cardiovascular disease or diabetes, no association was found between an increase in cardiovascular events and tocilizumab treatment, report Seoyoung C. Kim, M.D., of Brigham and Women's Hospital in Boston, and colleagues.

Rheumatoid arthritis patients have a nearly two-fold increased risk of cardiovascular disease and cardiovascular mortality as compared to the general population. Tocilizumab, an interleukin-6 receptor antagonist and a mainstay biologic for rheumatoid arthritis, has been associated with increasing LDL cholesterol levels. That juxtaposition is a focus of this study that compares the risk of cardiovascular events in patients who have just started tocilizumab as compared to those who just started TNFi therapy.

The study

This study is based on an analysis of claims data and included 28,028 adults (mean age between 51-72 years) with rheumatoid arthritis who had previously been on a biologic but were starting tocilizumab (9,218 patients) or a TNF inhibitor (18,810 patients). The study period lasted between 4.5 and 7 years.

Researchers found no increase in cardiovascular disease risk or stroke - which were the primary end points in this study - between patients starting on tocilizumab and patients starting on TNF inhibitors. Nor did they find an increased risk of secondary end points - myocardial infarction, stroke, acute coronary syndrome, coronary revascularization, heart failure and all-cause mortality - in tocilizumab initiators compared with TNFi initiators.

At baseline, 14.3% of patients on tocilizumab and 13.5% of patients on TNF inhibitors had cardiovascular disease and during the study period, 125 cardiovascular events occurred. The incidence of myocardial infarction or stroke was 0.52 per 100 person-years in the tocilizumab cohort and 0.59 per 100 person-years in the TNFi group.

The risk of cardiovascular events associated with tocilizumab use versus TNFi use was similar across all three databases, with a combined HR of 0.84 (95% confidence interval 0.56–1.26). Kaplan-Meier graphs confirmed that there were no statistical differences between outcomes in the tocilizumab group verses the tumor necrosis factor inhibitor cohort.

When myocardial infarction and stroke were looked at individually, the hazard ratios associated with tocilizumab and tumor necrosis factor inhibitor therapy were 0.70 (95% confidence interval 0.37-1.34 P=1.0) and 0.94 (95% confidence interval 0.56-1.59 P=0.6) respectively.

Subgroup analysis also revealed no higher risk of composite cardiovascular events between tocilizumab and tumor necrosis factor inhibitors therapy groups in patients over 60 years of age, those with pre-existing cardiovascular disease, diabetes or on methotrexate.

Implications for physicians

Even though tocilizumab treatment has been associated with increases in low-density lipoprotein (LDL) cholesterol levels in patients with rheumatoid arthritis, it doesn’t appear to increase the risk of cardiovascular disease when compared to treatment with tumor necrosis factor inhibitors.

Researchers did find a numeric decrease in risk. “This study has important clinical implications. While elevations in lipid levels occur in patients treated with tocilizumab, such increases do not appear to be associated with an increased risk of clinical cardiovascular events,” researchers wrote.

Disclosures:

Genentech provided funding for this study.

References:

Seoyoung C. Kim, Daniel H. Solomon, James R. Rogers, et al. “Cardiovascular safety of tocilizumab versus tumor necrosis factor inhibitors in patients with rheumatoid arthritis: A multi-database cohort study.” Arthritis & Rheumatology. Vol. 69, No. 6, June 2017, pp 1154–1164
DOI 10.1002/art.40084