| Project/Area Number |
17K11032
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Toho University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中川 晃一 東邦大学, 医学部, 教授 (30400823)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 関節リウマチ / 酸化ストレス / 寛解予測 / バイオマーカー / 関節破壊 / 活性酸素種 / トシリズマブ / 整形外科学 |
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| Outline of Final Research Achievements |
To verify whether serum levels of reactive oxygen metabolites (ROM) are predictive of future clinical remission in patients with rheumatoid arthritis (RA) receiving tocilizumab (TCZ) therapy. A total of 46 patients with RA receiving TCZ therapy were enrolled in this study. Patients were divided into remission and non-remission groups based on DAS28 at 52 weeks. Associations between serum levels of ROM, CRP, and MMP-3 at 4 and 12 weeks and the DAS-remission at 52 weeks were investigated.
There were no significant differences in CRP and MMP-3 between DAS-remission and non-remission groups at 12 weeks. However, ROM in DAS-remission group were significantly lower than those in the non-remission group. For ROM, an AUC of the ROC curve was 0.735 and the cut-off value was 305.5 U.Carr (sensitivity: 70.0%, specificity: 72.2%). A multivariate logistic regression analysis revealed that ROM at 12 weeks was associated with DAS-remission at 52 weeks (OR: 6.067, 95% CI: 1.305-28.203).
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| Academic Significance and Societal Importance of the Research Achievements |
IL-6受容体抗体のトシリズマブ(TCZ)は関節リウマチ(RA)患者に広く使用されているバイオ製剤である。しかしながら、TCZはCRPなどの急性反応物質の産生を強力に抑制する。このため実臨床ではCRPと臨床症状との乖離が見られることがあり、寛解予測のためのバイオマーカーの開発が望まれている。
本研究の結果、TCZ治療開始後12週における血中酸化ストレスマーカーであるROMが52週のDAS寛解を予測することが明らかとなった。治療効果判定にしばしば用いられるCRP, MMP-3はDAS寛解とは関連がなかったことから、ROMはTCZ治療早期寛解予測のバイオマーカーとして有用と考えられる。
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