Journal
ARTHRITIS & RHEUMATOLOGY
Volume 67, Issue 8, Pages 2056-2060Publisher
WILEY
DOI: 10.1002/art.39164
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Funding
- Ministry of Health, Labor, and Welfare of Japan (Health and Labor Sciences Research Grant for Research on Development of New Drugs [H24-bio-ippan-002]
- Abbott Japan
- Bristol-Myers K.K.
- Pfizer Japan
- Mitsubishi Tanabe Pharma
- Chugai Pharmaceutical
- Astellas Pharma
- Janssen Pharmaceutical K.K.
- Santen Pharmaceutical
- UCB Japan
- Eisai
- Takeda Pharmaceutical
- Daiichi Sankyo
- AbbVie
- Ono Pharmaceutical
- Teijin Pharma
- Eli Lilly Japan K.K.
- Asahi Kasei Pharma
- Novartis Pharma K.K
- Asahi Kasei Medical K.K.
- Astra Zeneca K.K.
- Celtrion
- Nipponkayaku
- Novartis Pharma K.K.
- Santen
- Pharmaceutical
- SymBio Pharmaceutical
- Taisho Toyama Pharmaceutical
- Mitsubishi Tanabe Pharm
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Objective. To investigate whether leucine-rich alpha(2)-glycoprotein (LRG) could be a biomarker for disease activity during interleukin-6 (IL-6) blockade treatment of rheumatoid arthritis (RA). Methods. In 59 RA patients who were treated with tocilizumab for 24 weeks, serum LRG levels were determined by enzyme-linked immunosorbent assay. RA disease activity was evaluated by the Clinical Disease Activity Index (CDAI). Receiver operating characteristic (ROC) curve analysis was used to examine the diagnostic performance of LRG and other biomarkers. In monkeys with experimental autoimmune arthritis, swollen joint counts, joint pathologic changes, and blood levels of C-reactive protein (CRP) and LRG were evaluated after treatment with anti-IL-6 receptor antibody. Results. Among tocilizumab-treated RA patients, those with active disease (CDAI >2.8) had significantly higher serum LRG levels compared to those whose disease was in remission. ROC curve analysis suggested that the LRG level was more useful than the CRP or matrix metalloproteinase 3 level or the erythrocyte sedimentation rate in discriminating between remission and active disease during therapy with tocilizumab. In monkeys treated with IL-6 blockade, joint scores were more closely correlated with LRG levels than with CRP levels. Histologic analysis of joints revealed that LRG levels correlated significantly with granulomatous tissue formation, cartilage degeneration, and bone destruction in IL-6 blockade-treated monkeys with low levels of CRP. Conclusion. Under conditions of IL-6 inhibition, LRG was more useful than other biomarkers in discriminating between active and inactive disease in human RA and in detecting joint inflammation in experimental arthritis. LRG may serve as a convenient biomarker for RA disease activity during IL-6 blockade treatment.
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