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Reduction of plasma IL-6 but not TNF-α by methotrexate in patients with early rheumatoid arthritis: a potential biomarker for radiographic progression

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Abstract

Objective

To determine the effect of methotrexate (MTX) on plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and to investigate their associations with clinical and radiographic responses in patients with early rheumatoid arthritis (RA).

Methods

Sixty-two untreated RA patients with the disease duration of ≤36 months in whom MTX was initiated were consecutively identified in our prospective RA cohort and included in this study. Concomitant use of prednisolone and synthetic disease-modifying anti-rheumatic drugs with MTX was allowed, but patients who used biological agents were excluded. Plasma IL-6 and TNF-α levels were measured at the time of diagnosis (baseline) and 1 year later. The relationships of the clinical and radiographic data with plasma levels of IL-6 and TNF-α were analyzed.

Results

The median age of the patients was 57 years, 49 patients were female, and the median disease duration was 3 months. Forty-six (74.2 %) patients were anti-cyclic citrullinated protein antibody-positive. Serum C-reactive protein (CRP), plasma IL-6, and DAS28 decreased significantly (p <0.001) after MTX treatment, but plasma TNF-α did not. Radiographic progression was significantly correlated with disease activity score and plasma IL-6 levels but not with CRP or TNF-α after MTX treatment. Patients with plasma IL-6 level above 4.03 pg/ml showed clinically relevant radiographic progression with a sensitivity of 91.7 % and a specificity of 88.0 %.

Conclusion

In this early RA cohort, we demonstrated a significant (p <0.001) reduction of plasma IL-6, but not TNF-α, during MTX treatment. The post-treatment IL-6 level was a strong indicator of radiographic progression.

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Acknowledgment

This study was in part supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (23701120). Cytokine measurement was supported by grant from Mitsubishi Tanabe Pharma Co.

Disclosures

NN, YK, and HK have no conflicts of interest to declare. MK has received non-restricted research grant from Abbott Japan Co., Ltd., Asahi Kasei Pharma Co., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Eizai Co., Ltd., Mitsubishi Tanabe Pharma Co., Santen Pharmaceutical Co., Ltd. and Wyeth. TT has received non-restricted research grant from Mitsubishi Tanabe Pharma.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Naoshi Nishina, Yuko Kaneko, Hideto Kameda, Masataka Kuwana & Tsutomu Takeuchi

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  1. Naoshi Nishina
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  2. Yuko Kaneko
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  3. Hideto Kameda
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  4. Masataka Kuwana
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  5. Tsutomu Takeuchi
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Correspondence to Tsutomu Takeuchi.

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Nishina, N., Kaneko, Y., Kameda, H. et al. Reduction of plasma IL-6 but not TNF-α by methotrexate in patients with early rheumatoid arthritis: a potential biomarker for radiographic progression. Clin Rheumatol 32, 1661–1666 (2013). https://doi.org/10.1007/s10067-013-2309-0

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  • DOI: https://doi.org/10.1007/s10067-013-2309-0

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