Tocilizumab Improves Left Ventricular Mass and Cardiac Output in Patients With Rheumatoid Arthritis. A Cohort Study

Kensuke Kume¹, Kanzo Amano¹, Susumu Yamada¹, Toshikatsu Kanazawa², Hiroshi Komori³, Hiroyuki Ohta⁴, Kuniki Amano⁵ and Noriko Kuwaba⁶, ¹Rheumatology, Hiroshima Clinic, Hiroshima, Japan, ²rheumatology, hiroshima clinic, hiroshima, Japan, ³internal medicine, hiroshima clinic, hiroshima, Japan, ⁴Medical Research, hiroshima clinic, Hiroshima, Japan, ⁵Rheumatology, Sky Clinic, Hiroshima, Japan, ⁶Medical Research, Sanki Clinical Link, Hiroshima, Japan

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Cardiovascular disease and tocilizumab

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy II

Session Type: Abstract Submissions (ACR)

Background/Purpose: Rheumatologists need to develop primary prevention strategies for cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients. We reported tocilizumab (TCZ) improved arterial stiffness as well as etanercept and adalimumab. RA is associated with an increased leftventricular mass index (LVMI), a strong marker of cardiovascular mortality.There is no evidence that TCZ effects on left ventricular (LV) morphology and function. To study the effect of TCZ plus methotrexate (MTX) on LV morphology and function in MTX resistant active RA patients, in a cohort study design.

Methods: RA patients were eligible if they had active disease despite treatment with MTX. All patients have no steroids, and no previous history of CVD. Consecutive 34 patients with moderate to severe active RA patients (DAS28>3.2) despite MTX were received TCZ plus MTX. LV morphology and function was assessed with cardio-MRI at baseline and 24 weeks follow-up. Cardiovascular risk factors and clinical data were collected at regular visits.

Results: 31 patients completed 24 weeks. Left ventricular mass index (LVMI) was attenuated significantly by TCZ (week 0-week24, −19.8±6.9 g/m²; p=0.0002). Cardiac output (CO) was attenuated significantly by TCZ (week 0-week24,-0.99 ± 1.4l/min). DAS28 and CRP improved significantly by TCZ (week 0-week24; DAS28: -2.35±0.85; CRP: 24.3±7.2 mg/l) (p<0.05). Surprisingly, the change of disease activity (DAS 28 and CRP) is no correlation with the change of LVMI or CO in this study. Observationally, 6 cases significantly improved right ventricular mass as well as left ventricular mass (20 % improved right ventricular mass index from baseline).

Conclusion: TCZ improved LVMI and CO in active RA despite MTX. TCZ improves LVMI and CO independently of its effects on disease activity. TCZ might be improved right ventricular mass. Interleukin (IL) 6 might be an important role of LV hypertrophy. TCZ, anti- Interleukin (IL) 6 receptor antibody, may prevent cardiovascular morbidity and mortality in RA.

References: 1) Tocilizumab monotherapy reduces arterial stiffness as effectively as etanercept or adalimumab monotherapy in rheumatoid arthritis: an open-label randomized controlled trial. Kume K, et al.J Rheumatol. 2011 Oct;38(10):2169-71. doi: 10.3899/jrheum.110340. Epub 2011 Aug 1.PMID: 21807781

2) Etanercept normalises left ventricular mass in patients with rheumatoid arthritis. Claire Immediato Daïen et al. Annals of the rheumatic diseases. 2013 Jun; 72(6); 881-7. doi: 10.1136/annrheumdis-2012-201489.

Conclusion:

Disclosure:

K. Kume,
None;

K. Amano,
None;

S. Yamada,
None;

T. Kanazawa,
None;

H. Komori,
None;

H. Ohta,
None;

K. Amano,
None;

N. Kuwaba,
None.

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