Tocilizumab Effects on Coagulation Factor XIII in Patients with Rheumatoid Arthritis

Abstract

Introduction: Rheumatoid arthritis (RA) is a chronic systemic auto-immune disease associated with a prothrombotic state. Tocilizumab, an interleukin-6 receptor inhibitor, is highly effective in controlling disease activity and thrombotic risk. Factor XIII (FXIII), involved in thrombotic complications, has been reported to be reduced in RA patients during maintenance treatment with tocilizumab, but no data are available before and after the drug administration. Thus, we investigated the effects of tocilizumab on FXIII, thrombin generation and inflammation in patients with RA naïve for the drug. Methods: We studied 15 consecutive adult patients with RA at baseline and 4 weeks after the onset of parenteral administration of tocilizumab, measuring disease activity and plasma levels of C-reactive protein (CRP), FXIII, and prothrombin fragments F1+2 by immunoenzymatic methods. Fifteen healthy subjects, sex-and age-matched with patients, served as normal controls for laboratory measurements. Results: At baseline, patients with established RA had a median DAS28 of 4.8 (3.2–8.3) and, compared to healthy controls, had higher plasma levels of CRP (p < 0.0001), FXIII (p = 0.017) and F1+2 (p < 0.0001). Four weeks after starting treatment with tocilizumab, based on the EULAR response criteria, eight patients were classifiable as responders and seven as non-responders. In responders, we observed a statistically significant reduction not only of the values of DAS28 and CRP (p = 0.012 for both), ut also of plasma levels of FXIII (p = 0.05) and F1+2 (p = 0.025). In non-responders, all the studied parameters were unchanged. Conclusion: The decrease of FXIII and F1+2 levels after tocilizumab treatment observed only in those patients who responded to the drug indicates that the effect of tocilizumab on the prothrombotic state is linked to the control of inflammation and disease activity and not to a direct effect of the drug, thus contributing to the reduction of the cardiovascular risk.