Olokizumab therapy and cardiovascular complications in rheumatoid arthritis

The development of cardiovascular disorders associated with atherosclerotic vascular lesions is a common complication of autoimmune rheumatic diseases (AIRDs), leading to a life expectancy decrease. Rheumatoid arthritis (RA) has a special place among the AIRDs, and the incidence of atherosclerotic vascular disease is 1.5-fold higher than in the general population, which is comparable to type 2 diabetes mellitus. This difference is due to the shared immunopathogenetic mechanisms of RA and atherosclerosis.

The aim of the study was to identify predictors of cardiovascular adverse events (CAE) during therapy with the interleukin 6 (IL-6) inhibitor olokizumab (OKZ) and to evaluate the cardioprotective potential of this monoclonal antibody.

In a pooled retrospective analysis of data from randomized and open-label, long-term clinical trials of the OKZ efficacy in patients with RA, we evaluated the effects of OKZ therapy on the incidence of CAE and the following lipid profile parameters: apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), lipoprotein-a (Lp(a)), adiponectin, homocysteine, and albumin.

During treatment with OKZ, an increased risk of CAE was independently associated with age over 60 years (hazard ratio (HR) – 1.59; 95% confidence interval (95% CI): 1.12–2.26), elevated (>30) body mass index (HR=1.75; 95% CI: 1.26–2.45), hypertention (HR=2.44; 95% CI: 1.46–4.06) and ApoA1 (>2.25 g/L) (OR=2.23; 95% CI: 1.05–4.72). During treatment with OKZ, an increase in adiponectin levels, a decrease in homocysteine, Lp(a), and no changes of the ApoB/ApoA1 ratio were noted. Favorable dynamics of cardiovascular risk biomarkers in patients receiving active therapy compared to placebo indicate a likely positive effect of OKZ on the cardiovascular system.

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