Objective. Patients with rheumatoid arthritis (RA) are twice as likely to experience sudden cardiac death compared with individuals without RA. Although the underlying mechanisms of this have not been clarified, evidence points to the effects of systemic inflammation on ventricular repolarization. Accordingly, prolongation of the corrected QT (QTc) interval is more frequent in patients with RA compared with individuals without RA also correlating with C-reactive protein (CRP) and predicting all-cause mortality. Tocilizumab (TCZ) is an anti-interleukin-6 receptor antibody that potently inhibits inflammatory activation in RA, with rapid normalization of acute-phase reactant levels, including the CRP level. Therefore, we hypothesized that TCZ may normalize the QTc interval by dampening systemic inflammation, thus reducing the risk of arrhythmia in patients with RA. Methods. Seventeen consecutive patients with active RA who were scheduled to receive TCZ once every 4 weeks underwent a clinical examination, electrocardiography, and blood sampling just before the first injection with TCZ and again after 3 months and 6 months of treatment. Results. At baseline, 76% of patients displayed prolongation of the QTc interval (mean ± SD 452.3 ± 35.8 msec). TCZ treatment was associated with a rapid and significant reduction of the QTc interval to mean values <440 msec (up to 428.1 ± 34.3 msec). Throughout the study, QTc interval shortening correlated with decreases in both the CRP level, and more strongly, with circulating tumor necrosis factor α level. Conclusion. These data provide further evidence of the close link between the degree of systemic inflammation and QTc interval duration in RA and also suggest an anti-arrhythmic potential for TCZ treatment, which may have a beneficial impact on the mortality of these patients.

Antiarrhythmic potential of anticytokine therapy in rheumatoid arthritis: Tocilizumab reduces corrected qt interval by controlling systemic inflammation

GENTILE, DANIELA;
2015

Abstract

Objective. Patients with rheumatoid arthritis (RA) are twice as likely to experience sudden cardiac death compared with individuals without RA. Although the underlying mechanisms of this have not been clarified, evidence points to the effects of systemic inflammation on ventricular repolarization. Accordingly, prolongation of the corrected QT (QTc) interval is more frequent in patients with RA compared with individuals without RA also correlating with C-reactive protein (CRP) and predicting all-cause mortality. Tocilizumab (TCZ) is an anti-interleukin-6 receptor antibody that potently inhibits inflammatory activation in RA, with rapid normalization of acute-phase reactant levels, including the CRP level. Therefore, we hypothesized that TCZ may normalize the QTc interval by dampening systemic inflammation, thus reducing the risk of arrhythmia in patients with RA. Methods. Seventeen consecutive patients with active RA who were scheduled to receive TCZ once every 4 weeks underwent a clinical examination, electrocardiography, and blood sampling just before the first injection with TCZ and again after 3 months and 6 months of treatment. Results. At baseline, 76% of patients displayed prolongation of the QTc interval (mean ± SD 452.3 ± 35.8 msec). TCZ treatment was associated with a rapid and significant reduction of the QTc interval to mean values <440 msec (up to 428.1 ± 34.3 msec). Throughout the study, QTc interval shortening correlated with decreases in both the CRP level, and more strongly, with circulating tumor necrosis factor α level. Conclusion. These data provide further evidence of the close link between the degree of systemic inflammation and QTc interval duration in RA and also suggest an anti-arrhythmic potential for TCZ treatment, which may have a beneficial impact on the mortality of these patients.
Lazzerini, Pietro Enea; Acampa, Maurizio; Capecchi, Pier Leopoldo; Fineschi, Irene; Selvi, Enrico; Moscadelli, Valentina; Zimbone, Stefania; Gentile, Daniela; Galeazzi, Mauro; Laghi Pasini, Franco
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/853025
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