Tofacitinib Improves Arterial Stiffness Despite up-Regulating Serum Cholesterol with Chronic Cardiovascular Disease in Methotrexate-Resistant Active Rheumatoid Arthritis Patients. a Cohort Study

Kensuke Kume¹, Kanzo Amano², Susumu Yamada², Toshikatsu Kanazawa³, Hiroshi Komori⁴, Kazuhiko Hatta⁵, Kuniki Amano⁶ and Noriko Kuwaba⁷, ¹20-16 Higashi Kannon, Nishi Ward, hiroshima clinic, Hiroshima, Japan, ²Rheumatology, Hiroshima Clinic, Hiroshima, Japan, ³rheumatology, hiroshima clinic, hiroshima, Japan, ⁴internal medicine, hiroshima clinic, hiroshima, Japan, ⁵Rheumatology, Hatta Clinic, Kure, Japan, ⁶Rheumatology, Sky Clinic, Hiroshima, Japan, ⁷Medical Research, Sanki Clinical Link, Hiroshima, Japan

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Arteriosclerosis, Cardiovascular disease, Cholesterol, rheumatoid arthritis (RA) and tofacitinib

Session Information

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy: Safety of Biologics and Small Molecules in Rheumatoid Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Patients with rheumatoid arthritis (RA) have an increased cardiovascular (CV) risk. We should have strategies for primary cardiovascularprevention in RA. Tofacitinib (Tofa) could possibly play a role in up-regulating levels of serum cholesterol¹.But there is no evidence of CV risk management about Tofa. To examine the effect of Tofa plus methotrexate (MTX) on arterial stiffness with CV disease in MTX resistant RA patients in a cohort study design.

Methods: 18 RA patients with moderate to severe active disease despite MTX treatment (disease activity score: DAS28>3.2) were received Tofa plus MTX. All patients have previous history of CV. Arterial stiffness was assessed with cardio-ankle vascular index (CAVI) and augmentation index corrected for a heart rate of 75 beats per minute (AIx@75) at baseline and 24 weeks follow-up. Clinical data were collected at regular visits. CAVI is very similar to pulse wave velocity (PWV), and CAVI measures arterial wall stiffness independent of blood pressure and it is superior to brachial ankle PWV as an index of arterial stiffness².No new all treatments(statin, low lipids drug, and etc.) were allowed.

Results: Treatment with Tofa attenuated the CAVI significantly from baseline to 24 weeks follow up(12.68 ± 1.77 and 10.48± 1.28%; p = 0.016). Treatment with Tofa attenuated the Aix@75 significantly from baseline to 24 weeks follow up(38.7 ± 8.6, 33.2 ± 3.6 %; p = 0.018). DAS 28-ESR score improved significantly from baseline to 24 weeks(5.11±1.33, 2.43±1.43: p=0.01). On the other hand, fasting serum total cholesterol TC was significantly increased from baseline to follow-up at 24 weeks (195±21.2mg/dL, 211±24.2mg/dL, p = 0.03). No patients suffered from new CV disease.

Conclusion: These findings suggest that combination therapy, Tofa with MTX not only reduced RA disease activity but also limited vascular damage despite up-regulating serum cholesterol with CV disease in patients MTX resistant active RA.

References: 1) Kremer J. et al. Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2013 Aug 20;159(4):253-61.

2) Takaki A et al. Cardio-ankle vascular index is superior to brachial-ankle pulse wave velocity as an index of arterial stiffness. Hypertens Res.2008 Jul; 31(7):1347-55

Disclosure:

K. Kume,
None;

K. Amano,
None;

S. Yamada,
None;

T. Kanazawa,
None;

H. Komori,
None;

K. Hatta,
None;

K. Amano,
None;

N. Kuwaba,
None.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tofacitinib-improves-arterial-stiffness-despite-up-regulating-serum-cholesterol-with-chronic-cardiovascular-disease-in-methotrexate-resistant-active-rheumatoid-arthritis-patients-a-cohort-study/