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AB0358 Serum GM-CSF Levels Are Significantly Associated with Interstitial Pneumonia in Biologic-Naive Patients with Rheumatoid Arthritis: A Single-Center Prospective Cohort Study (Keio First-Bio Cohort Study)
  1. K. Izumi1,2,
  2. M. Hashizume3,
  3. K. Yoshimoto1,
  4. Y. Kaneko1,
  5. H. Yasuoka1,
  6. K. Suzuki1,
  7. K. Yamaoka1,
  8. T. Takeuchi1
  1. 1Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine
  2. 2Department of Connective Tissue Diseases, National Tokyo Medical Center, Tokyo
  3. 3Product Research Department, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Gotemba, Japan


Background Interstitial pneumonia (IP) is one of the most critical complications in rheumatoid arthritis (RA).

Objectives We aimed to explore the associations between IP and serum cytokines in biologic-naive patients with RA.

Methods Consecutive biologic-naive patients with RA were enrolled in our prospective cohort study at the timing of initiating biologics. Our cohort started in February 2010, and the patients were analysed as of April 2012. Before initiating biologics, we evaluated chest X-rays for all of the patients, and if IP was suspected, a chest computed tomographic (CT) scan was taken. We assessed variables at the enrollment of our cohort including the patients' characteristics (age, disease duration, prednisolone (PSL) dose, methotrexate (MTX) dose, CDAI, HAQ, mTSS) and serum biomarker levels (IgG, IgM, IgM-RF, ACPA, CRP, MMP-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-17, TNF-α, VEGF, sICAM-1, BAP, osteonectin, osteopontin) to extract factors associated with CT scan-proven IP using univariate analyses. The extracted variables (P<0.1) were applied to a stepwise selection method, and the selected variables were entered into a multivariate logistic regression model to obtain factors associated with IP.

Results A total of 127 patients (108 females and 19 males) were included in our study. The mean age and disease duration of the patients were 56.2±12.9 years and 6.7±7.7 years, respectively. CT scan-proven IP was noted in 17 patients. PSL was used in 33 patients and MTX was used in 110. In the univariate analyses, age, PSL dose, MTX dose, GM-CSF, IL-1β, and VEGF were significantly associated (P<0.05), and IL-8 and TNF-α tended to be associated with IP (P<0.1). In the multivariate analyses, age (OR 1.093, 95% CI 1.033-1.173), MTX dose (0.829, 0.705-0.969), and the levels of GM-CSF (1.376, 1.081-2.042) were identified as factors associated with IP.

Conclusions The high serum levels of GM-CSF as well as high age and low MTX dose are significantly associated with IP in biologic-naive patients with RA.

Disclosure of Interest K. Izumi: None declared, M. Hashizume Employee of: Chugai Pharmaceutical Co., Ltd., K. Yoshimoto: None declared, Y. Kaneko: None declared, H. Yasuoka: None declared, K. Suzuki: None declared, K. Yamaoka: None declared, T. Takeuchi Grant/research support from: Abbott Japan Co., Ltd., Astellas Pharma, Bristol-Myers K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Sanofi–Aventis K.K., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahikasei Pharma Corp., and Taisho Toyama Pharmaceutical Co., Ltd., Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K.,abbivie GK, Daiichi Sankyo Co.,Ltd., Speakers bureau: Abbott Japan Co., Ltd., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Astellas Pharma, and Daiichi Sankyo Co.,Ltd.

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