Heart Rate-corrected QT Interval Duration in Rheumatoid Arthritis and Its Reduction with Treatment with the Interleukin 6 Inhibitor Tocilizumab.

Abstract

Individuals with rheumatoid arthritis (RA) are at a heightened risk of sudden cardiac death, an outcome increased in those with prolongation of the corrected electrocardiographic QT interval (QTc). We compared QTc between patients with RA and demographically matched controls and studied the change in QTc after treatment with the interleukin 6 inhibitor tocilizumab (TCZ). Standard 12-lead electrocardiograms were obtained and QTc was measured in patients with RA at baseline and after 24 weeks of TCZ treatment, then compared with non-RA controls who were frequency-matched on age and sex. Indicators of the baseline QTc and predictors of change in QTc were studied using multivariable linear regression. A total of 94 RA and 42 non-RA controls were studied. The average baseline QTc was 10 ms longer in the RA group vs controls (422 vs 412 ms, respectively; p < 0.001) and decreased to an average of 406 ms with treatment (p < 0.001). Baseline QTc was significantly and independently higher among those with anticyclic citrullinated peptide antibodies seropositivity, higher swollen joint counts, and higher levels of C-reactive protein (CRP) and matrix metalloproteinase 3. Each log unit decrease in CRP with treatment was associated with an average reduction in QTc of 2.9 ms (p = 0.002) after adjusting for age and baseline QTc. Clinical response measures were not associated with the change in QTc. The marked normalization of QTc observed with TCZ treatment, and its close parallel with CRP reduction, support the premise that systemic inflammation contributes to cardiac repolarization abnormalities in RA that may be amenable to treatment.