title: Antiarrhythmic potential of anticytokine therapy in rheumatoid arthritis: tocilizumab reduces corrected QT interval by controlling systemic inflammation.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Siena, Siena, Italy.
authors.forename: Pietro Enea
authors.initials: PE
authors.lastname: Lazzerini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Acampa
authors.forename: Pier Leopoldo
authors.initials: PL
authors.lastname: Capecchi
authors.forename: Irene
authors.initials: I
authors.lastname: Fineschi
authors.forename: Enrico
authors.initials: E
authors.lastname: Selvi
authors.forename: Valentina
authors.initials: V
authors.lastname: Moscadelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Zimbone
authors.forename: Daniela
authors.initials: D
authors.lastname: Gentile
authors.forename: Mauro
authors.initials: M
authors.lastname: Galeazzi
authors.forename: Franco
authors.initials: F
authors.lastname: Laghi-Pasini
mesh_terms: D000200:Action Potentials; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000097:blood; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000097:blood; D008297:Male; D008875:Middle Aged; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D016207:Cytokines; C508603:IL6R protein, human; D018836:Inflammation Mediators; D019947:Receptors, Interleukin-6; D002097:C-Reactive Protein; C502936:tocilizumab