Cardiovascular Risk in Tocilizumab Therapy for RA

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Observation and research have confirmed that patients with rheumatoid arthritis (RA) are at greater risk of cardiovascular disease than their peers of similar age and gender, and that traditional risk factors and chronic inflammation associated with RA apparently play a significant role in that risk. However, predicting which patients with rheumatoid arthritis are at greater risk of cardiovascular events and understanding the effects of RA therapies on risk are not known, but published and ongoing research efforts are exploring possible answers.

One dilemma is why traditional risk factors, such as lipids, don’t seem to always be predictive of which patients with RA are at greater risk of cardiovascular events. In some trials, certain therapies lower inflammation but also increase total cholesterol and LDL cholesterol, but whether those increases are clinically important is not understood. Additionally, no validated methods exist that can factor inflammation into the cardiovascular risk equation in RA, according to an editorial by Katherine Liao, MD, MPH, and Daniel Solomon, MD, MPH, in the February issue of Arthritis & Rheumatology.¹

One of the most recent efforts looking at risk factors for major cardiovascular events for patients being treated with a specific RA therapy was published by Vijay Rao, MD, PhD, et al in Arthritis & Rheumatology.² The retrospective post hoc analysis evaluated the relationship between traditional markers (i.e., lipids) and RA-specific parameters and cardiovascular risk in patients treated with the anti-IL-6 monoclonal antibody tocilizumab (TCZ).

Baseline Characteristics

The analysis looked at pooled data for 3,896 adult patients enrolled in several randomized controlled trials and extension studies. Researchers included patients who had moderate to severe RA and were treated with one or more intravenous doses of TCZ (4 mg/kg or 8 mg/kg) every four weeks in combination with methotrexate or other disease-modifying anti-rheumatic drugs (DMARDs) or as monotherapy. Mean follow-up was 3.6 years; 50 cardiovascular events were independently adjudicated.

According to the authors, the analysis indicated that several baseline characteristics were independently associated with a greater risk of cardiovascular events: a history of cardiac disorders, age at baseline, the baseline atherogenic index and baseline RA disease activity as assessed by DAS28.

After 24 weeks of TCZ therapy, those patients who had greater reductions in their disease activity had a statistically significantly lower risk of events. Disease activity was assessed by increases in DAS28, swollen joint count and tender joint count from baseline to Week 24. Those patients who had less robust therapeutic responses to TCZ from baseline to Week 24 were at higher risk of events, the authors said.

An increasingly recognized paradox for physicians treating patients with RA is that cholesterol is inversely related to risk of cardiovascular disease in patients with RA who are not treated.

The baseline and Week 24 levels of the markers of inflammation (i.e., erythrocyte sedimentation rate [ESR] and C-reactive protein changes) were also evaluated. Changes in the IL-6 level and the ESR were not statistically significantly associated with future development of major cardiovascular events over 24 weeks of therapy.