Antiarrhythmic Potential of Anticytokine Therapy in Rheumatoid Arthritis: Tocilizumab Reduces Corrected QT Interval by Controlling Systemic Inflammation

• Published in: Arthritis care & research (2010) 2015-03, Vol.67 (3), p.332-339
• Main Authors: Lazzerini, Pietro Enea, Acampa, Maurizio, Capecchi, Pier Leopoldo, Fineschi, Irene, Selvi, Enrico, Moscadelli, Valentina, Zimbone, Stefania, Gentile, Daniela, Galeazzi, Mauro, Laghi‐Pasini, Franco
• Format: Article
• Language: English
• Subjects: Action Potentials; Adult; Anti-Arrhythmia Agents - therapeutic use; Antibodies, Monoclonal, Humanized - therapeutic use; Antirheumatic Agents - therapeutic use; Arrhythmias, Cardiac - diagnosis; Arrhythmias, Cardiac - immunology; Arrhythmias, Cardiac - physiopathology; Arrhythmias, Cardiac - prevention & control; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - physiopathology; C-Reactive Protein - metabolism; Cytokines - antagonists & inhibitors; Cytokines - blood; Electrocardiography; Female; Heart Conduction System - drug effects; Heart Conduction System - physiopathology; Humans; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - blood; Male; Middle Aged; Receptors, Interleukin-6 - antagonists & inhibitors; Signal Transduction - drug effects; Time Factors; Treatment Outcome
• ISSN: 2151-464X; 2151-4658
• DOI: 10.1002/acr.22455

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