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Tofacitinib improves atherosclerosis despite up-regulating serum cholesterol in patients with active rheumatoid arthritis: a cohort study

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Abstract

Patients with rheumatoid arthritis (RA) have an increased cardiovascular (CV) risk. This study aimed to analyze the effects of Tofacitinib treatment, a Janus kinase inhibitor, on atherosclerosis in patients with RA. Patients with an active RA (28-joint disease activity score–erythrocyte sedimentation rate > 3.2) despite methotrexate (MTX) treatment 12 mg/week were included in this open-label prospective study and started on Tofacitinib (10 mg/day, 5 mg twice/day). Japanese guideline does not allow high dose of MTX. All patients used a stable dosage of MTX, steroids, and statins or lipid-lowering drugs. The primary endpoint was the comparison of the carotid intima-media thickness (CIMT) at the baseline and 54 weeks after Tofa treatment. Clinical data were collected at regular visits. Forty-six patients completed this study. CIMT did not significantly change from baseline to 54 weeks (1.09 ± 0.69 and 1.08 ± 0.78 mm, p = 0.82). In 12 patients who had atherosclerosis at baseline (carotid intima-media thickness > 1.10 mm), there was a significant decrease in CIMT (0.05± 0.026 mm; p < 0.05). However, the decrease in CIMT was of limited clinical significance. Tofacitinib increased fasting total cholesterol levels from baseline to 54 weeks (216 ± 25.3 and 234 ± 28.8 mg/dL, p < 0.01). Tofacitinib affects atherosclerosis in patients with active RA The CIMT in RA patients was stable. Tofacitinib decreased the CIMT of patients who had increased CIMT at baseline. Tofacitinib reduced RA disease activity and limited vascular damage despite up-regulating cholesterol in patients with an active RA.

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Acknowledgements

Other contributors: The authors thank Naohiko Matsumoto (department of medical research, Hiroshima Clinic) for expert statistical analyses, and Hiroshi Komori (department of internal medicine, Hiroshima Clinic), for editing assistance in this study.

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Authors and Affiliations

  1. Department of Rheumatology, Hiroshima Clinic, Higashi Kannon 20-16, Nishi-ku, Hiroshima, Japan

    Kensuke Kume, Kanzo Amano, Susumu Yamada & Toshikatsu Kanazawa

  2. Department of Medical Research, Hiroshima Clinic, Hiroshima, Japan

    Hiroyuki Ohta

  3. Department of Rheumatology, Hatta Clinic, Kure, Japan

    Kazuhiko Hatta

  4. Department of Rheumatology and Immunology, Sky Clinic, Hiroshima, Japan

    Kuniki Amano

  5. Department of Medical Research, EP Sogo, Hiroshima, Japan

    Noriko Kuwaba

Authors
  1. Kensuke Kume
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  2. Kanzo Amano
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  3. Susumu Yamada
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  4. Toshikatsu Kanazawa
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  5. Hiroyuki Ohta
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  6. Kazuhiko Hatta
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  7. Kuniki Amano
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  8. Noriko Kuwaba
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Contributions

Study conception and design: KK. Acquisition of data: KK, KA, SY, TK, KH, and KA. Analysis and interpretation of data: KK, KA, HO, and NK.

Corresponding author

Correspondence to Kensuke Kume.

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Conflict of interest

Author Kensuke Kume, Kanzo Amano, Susumu Yamada, Toshikatsu Kanazawa, Hiroyuki Ohta, Kazuhiko Hatta, Kuniki Amano, and Noriko Kuwaba declare they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Hiroshima Clinic ethical committee on 2013/August/5th) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Funding

Approved by Hiroshima Clinic. Statement of role of funding source in publication: Dr. Kensuke Kume and Kanzo Amano have received a speaking fee from Ono Pharmacy and Eisai Pharmacy (< 10,000 dollars).

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Kume, K., Amano, K., Yamada, S. et al. Tofacitinib improves atherosclerosis despite up-regulating serum cholesterol in patients with active rheumatoid arthritis: a cohort study. Rheumatol Int 37, 2079–2085 (2017). https://doi.org/10.1007/s00296-017-3844-9

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  • DOI: https://doi.org/10.1007/s00296-017-3844-9

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