Observational associations between inflammation and cardiovascular disease are interesting, but randomised experimental data are lacking. We investigated the effect of the IL-6 receptor blocker tocilizumab on N terminal pro B type natriuretic peptide (NT-proBNP) and high sensitivity troponin T (hsTnT) in rheumatoid arthritis (RA) patients.
A post-hoc study was performed in a subset of patients with moderate to severe RA participating in a randomised controlled trial. The effect of tocilizumab on cardiac biomarkers was determined using stored serum (baseline and 24 weeks) in recipients of tocilizumab (8 mg/kg every 4 weeks plus DMARDs; n = 225) or placebo (every 4 weeks plus DMARDs; n = 132).
Median NT-proBNP and hsTnT concentrations at baseline were 100 pg/ml and 5.7 pg/ml, respectively. NT-proBNP decreased in both study arms (median at 24 weeks 77 pg/ml in the placebo arm, 79 pg/ml in the tocilizumab arm; p<0.001 for the decrease in both arms), and decreased to a similar extent comparing study arms (tocilizumab effect: -5.5%, p=0.55). hsTnT also decreased in both study arms (median at 24 weeks 3.1 pg/ml in the placebo arm, 4.4 pg/ml in the tocilizumab arm; p<0.001 for the decrease in both arms). The extent of the reduction in hsTnT was greater in the placebo group (tocilizumab effect: +23.3%, p=0.002). Change in NT-proBNP, but not hsTnT, correlated modestly with change in CRP (r = 0.17, p=0.013).
NCT00106574.
These data argue against a rapid preferential benefit of IL-6 blockade on these specific surrogate markers of cardiovascular risk, but may be consistent with a general cardiovascular benefit of improved RA treatment. CLINICAL TRIALS.