Background/Purpose: Individuals with rheumatoid arthritis (RA) have a two-fold higher risk of sudden death than the healthy age- and sex-matched general population. Although the underlying mechanisms have not been clarified, evidence suggests the effects of systemic inflammation on ventricular repolarization. Consequently, prolongation of the corrected QT (QTc) interval in patients with RA is more frequent than in individuals without RA. We prospectively evaluated the impact of tocilizumab (TCZ) treatment on the QTc interval in patients with RA without cardiac symptoms and investigated the associations of QTc interval with RA disease activity and severity measures.

Methods: This was a prospective interventional study from March 2012 to December 2015 in Itabashi Chuo Medical Center. The RA study inclusion criteria were fulfillment of American College of Rheumatology (ACR) for the classification of RA or 2010 ACR/EULAR RA criteria. Exclusion criteria were diabetes, previous cardiovascular events, hypertension, dyslipidemia, cardiomyopathy, renal disease, and current atrial fibrillation. Healthy age- and sex-matched individuals without cardiac symptoms were selected as controls. TCZ (8 mg/kg IV every 4 weeks or 162 mg SC biweekly) was prescribed for patients with active RA with an inadequate clinical response to methotrexate. Electrocardiography and clinical and biological monitoring were performed at baseline and 24 weeks after TCZ treatment in patients with RA. A QTc interval of 440 ms was considered prolonged in this study.

Results: We enrolled 94 patients with RA (mean age, 56.4±10.4 years; 85% female) and 40 healthy age- and sex-matched controls (mean age, 55.6±9.4 years; 86% female). 20% and 14% of RA patients received anti-hypertensive and anti-hyperlipidemia therapy respectively. The 24-week disease activity scores (DAS28-ESR) were significantly lower than those at baseline. We identified 8 (8.5%) patients with a prolonged QTc interval. However, the QTc interval at baseline was higher in the control group (422.3±25.8 ms vs 402.3±31.2 ms; p = 0.04). The QTc interval decreased 20 ms from baseline to 24 weeks (p = 0.001) following TCZ treatment. The percentage change in the QTc interval significantly correlated with C-reactive protein (CRP), anti-cyclic citrullinated peptide antibody (ACPA), and DAS28 at baseline (ρ = −0.43, p < 0.0001; ρ = −0.23, p = 0.024; ρ = −0.21, p = 0.04, respectively). The percentage change in the QTc interval strongly correlated with that in matrix metalloproteinase-3 (MMP3) after TCZ therapy (ρ = 0.38, p = 0.001). After adjusting for confounding variables, such as age, RA duration, ACPA, and CRP, the association of percentage change in the QTc interval with ACPA remained significant (p = 0.004, R²= 0.29).

Conclusion: The data suggest that the anti-arrhythmic potential for TCZ therapy may have a beneficial impact on patients with RA. The data may provide further evidence of the degree of association between ACPA and QTc interval. Furthermore, MMP3, which may affect ventricular remodeling, might contribute to the QTc interval.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tocilizumab-therapy-reduces-corrected-qt-interval-in-patients-with-rheumatoid-arthritis-without-cardiac-symptoms/