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Serum level of reactive oxygen metabolites (ROM) at 12 weeks of treatment with biologic agents for rheumatoid arthritis is a novel predictor for 52-week remission

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Abstract

We have shown that serum levels of reactive oxygen metabolites (ROM) were associated with C-reactive protein (CRP) and disease activity score based on the examination of 28 joints (DAS28) in patients with rheumatoid arthritis (RA); however, their clinical significance as biomarkers has not been elucidated. Forty-eight biologic agent (BA)-naïve RA patients were included in this study. Associations between serum levels of ROM, CRP, matrix metalloproteinase-3 (MMP-3), DAS28-erythrocyte sedimentation rate (ESR), and Health Assessment Questionnaire (HAQ) at 12 weeks of treatment and DAS28 (ESR) remission at 52 weeks (52-week remission) were investigated. The ROM serum level at baseline in the remission group (n = 34) was 527 ± 132 Carratelli units (U.Carr) (normal range <300), decreased to 335 ± 79.1 at 4 weeks, and remained low thereafter. In the non-remission group (n = 14), the ROM serum level at baseline was 592 ± 113 U.Carr, decreased to 450 ± 152 at 4 weeks, but gradually increased thereafter. Among significantly different factors at 12 weeks between the remission and non-remission groups, ROM and DAS28 (ESR) were identified as predictors of 52-week remission (p = 0.045, odds ratio 0.985, 95% confidence interval 0.97–1.000 for ROM). The cutoff value of ROM was determined to be 381.5 U.Carr (sensitivity 0.833, specificity 0.871). These results show that serum ROM levels can predict remission with high accuracy and could be a useful biomarker for achieving remission in the current treat-to-target strategy for RA.

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Acknowledgements

The authors are grateful to Mr. Keiichiro Terayama for his assistance with statistical analyses. This work was supported in part by Grant-in-Aid from the Ministry of Education, Science, Technology, Sports and Culture of Japan (no. 23592233 to A.N.) and the Research Promotion Grant from Toho University Graduate School of Medicine (no. 15-03 to A.N.).

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Authors and Affiliations

  1. Department of Orthopaedics, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura-shi, Chiba, 285-8741, Japan

    Arata Nakajima, Masato Sonobe, Hiroshi Takahashi, Masahiko Saito & Koichi Nakagawa

  2. Department of Rheumatology, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura-shi, Chiba, 285-8741, Japan

    Arata Nakajima

  3. Department of General Medical Sciences, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba, 260-8677, Japan

    Yasuchika Aoki

  4. Department of Orthopaedic Surgery, Eastern Chiba Medical Center, 3-6-2 Okayamadai, Togane-shi, Chiba, 283-8686, Japan

    Yasuchika Aoki

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  1. Arata Nakajima
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  2. Yasuchika Aoki
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  3. Masato Sonobe
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  4. Hiroshi Takahashi
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  5. Masahiko Saito
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  6. Koichi Nakagawa
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Correspondence to Arata Nakajima.

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Approval for the study was received from the Institutional Review Board at Toho University, and all patients gave their consent before their inclusion in this study. All activities were performed in accordance with the ethical standards set forth in the Declaration of Helsinki.

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Nakajima, A., Aoki, Y., Sonobe, M. et al. Serum level of reactive oxygen metabolites (ROM) at 12 weeks of treatment with biologic agents for rheumatoid arthritis is a novel predictor for 52-week remission. Clin Rheumatol 36, 309–315 (2017). https://doi.org/10.1007/s10067-016-3479-3

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  • DOI: https://doi.org/10.1007/s10067-016-3479-3

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