4.6 Article

Baseline Serum Osteopontin Levels Predict the Clinical Effectiveness of Tocilizumab but Not Infliximab in Biologic-Naive Patients with Rheumatoid Arthritis: A Single-Center Prospective Study at 1 Year (the Keio First-Bio Cohort Study)

Journal

PLOS ONE
Volume 10, Issue 12, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0145468

Keywords

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Funding

  1. Astellas Pharma Inc
  2. Bristol-Myers KK
  3. Chugai Pharmaceutical Co, Ltd
  4. Daiichi Sankyo Co, Ltd
  5. Eisai Co, Ltd
  6. Mitsubishi Tanabe Pharma Corp
  7. Pfizer Japan
  8. Santen Pharmaceutical Co, Ltd
  9. Takeda Pharmaceutical Co, Ltd
  10. Teijin Pharma Ltd
  11. AbbVie GK
  12. Asahi Kasei Pharma Corp
  13. Taisho Toyama Pharmaceutical Co, Ltd
  14. SymBio Pharmaceuticals Ltd
  15. Janssen Pharmaceutical KK
  16. Pfizer Japan Inc
  17. Astra Zeneca KK
  18. Eli Lilly Japan KK
  19. Novartis Pharma KK
  20. Asahi Kasei Medical Co, Ltd
  21. Grants-in-Aid for Scientific Research [15K21368] Funding Source: KAKEN

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Objective To explore the baseline predictors of clinical effectiveness after tocilizumab or infliximab treatment in biologic-naive rheumatoid arthritis patients. Methods Consecutive biologic-naive patients with rheumatoid arthritis initiating infliximab (n = 57) or tocilizumab (n = 70) treatment were included in our prospective cohort study. Our cohort started in February 2010, and the patients observed for at least 1 year as of April 2013 were analysed. We assessed baseline variables including patients' characteristics (age, sex, disease duration, prednisolone dose, methotrexate dose, other disease-modifying antirheumatic drug use, Clinical Disease Activity Index [CDAI]) and serum biomarker levels (C-reactive protein, immunoglobulin M-rheumatoid factor, anti-cyclic citrullinated protein/peptide antibodies, interferon-gamma, interleukin (IL)-1 beta, IL-2, IL-6, IL-8, IL-10, IL-17, tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, bone alkaline phosphatase, osteonectin, osteopontin) to extract factors associated with clinical remission (CDAI <= 2.8) at 1 year using univariate analyses, and the extracted factors were entered into a multivariate logistic regression model. Similar analyses were also performed for Simplified Disease Activity Index (SDAI) remission (<= 3.3) and Disease Activity Score with 28 joint counts, erythrocyte sedimentation rate (DAS28-ESR) remission (< 2.6). Results There were no significant differences in the baseline characteristics except for methotrexate use between the groups. In the multivariate analyses, the low baseline osteopontin levels (OR 0.9145, 95% CI 0.8399-0.9857) were identified as predictors of CDAI remission in the tocilizumab group, whereas no predictors of CDAI remission were found in the infliximab group. Similar results were obtained when using SDAI and DAS28-ESR remission criteria. Conclusion Baseline low serum osteopontin levels predict clinical remission 1 year after tocilizumab treatment and not infliximab treatment in biologic-naive patients with rheumatoid arthritis. Our prediction model provided insights into how to optimize the choice of biologics and warrants external validation in other cohorts.

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