期刊
RHEUMATOLOGY INTERNATIONAL
卷 36, 期 3, 页码 349-357出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00296-015-3379-x
关键词
Rheumatoid arthritis; Tocilizumab; Predictor; Biomarker; Fibrinogen; D-dimer; Interleukin-1 beta
类别
资金
- Chugai Pharmaceutical Co., Ltd.
- Mitsubishi Tanabe Pharma Co.
- Astellas Pharma Inc.
- Abbvie GK, Eisai Co., Ltd.
- MSD K.K.
- Bristol-Myers K.K.
- Takeda Pharmaceutical Co., Ltd.
- Janssen Pharmaceutical K.K.
- Abbvie GK
- Teijin Pharma Ltd.
- Ono Pharmaceutical Co., Ltd.
- Nippon Zoki Pharmaceutical Co., Ltd.
- Daiichi Sankyo Co., Ltd.
- Hisamitsu Pharmaceutical Co., Inc.
- Osteopharma Inc.
- Asahi Kasei Pharma Co.
- Taisho Toyama Pharmaceutical Co., Ltd.
- Eli Lilly Japan K.K.
- Pfizer Japan Inc.
- Grants-in-Aid for Scientific Research [26462314] Funding Source: KAKEN
Predicting the responses of patients with rheumatoid arthritis (RA) to tocilizumab is difficult, because inflammatory markers such as C-reactive protein rapidly normalize regardless of clinical efficacy. We aimed to identify factors that could predict response to tocilizumab. Sixty-five patients completed 52 weeks of tocilizumab therapy. Serum fibrinogen, D-dimer and interleukin (IL)-1 beta levels were measured at baseline and after 4 weeks of therapy. Clinical responses to tocilizumab were assessed using disease activity score 28-erythrocyte sedimentation rate and the clinical disease activity index at baseline and after 52 weeks of therapy (UMIN Clinical Trials Registry No. UMIN000002246). Mean age was 60.5 years (range 22-85 years). Mean disease duration was 11.2 years (range 0-45 years). All patients had moderate-to-severe disease activity and were resistant to disease-modifying anti rheumatic drugs and/or other biologics. Baseline IL-1 beta levels were significantly lower in responders than in non responders (p = 0.045), but multiple logistic regression analysis found no significant difference (adjusted odds ratio 2.74; 95 % confidence interval 0.84-8.95; p = 0.096). Low D-dimer and IL-1 beta levels at 4 weeks predicted greater decrease in disease activity after 52 weeks of treatment (p = 0.005 and p < 0.001, respectively). Effects of tocilizumab at 52 weeks could be predicted from D-dimer and IL-1 beta levels after 4 weeks of tocilizumab treatment. These markers might be more useful than current inflammatory markers for early-stage prediction of response to tocilizumab in RA.
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