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THU0124 Importance of monitoring of C-reactive protein level to predict achievement of better clinical outcome during treatment with tocilizumab in patients with rheumatoid arthritis
  1. T. Kojima1,1,
  2. K. Funahashi1,
  3. N. Takahashi1,
  4. D. Kato1,
  5. H. Matsubara1,
  6. Y. Hattori1,
  7. Y. Yabe2,
  8. N. Ishiguro1
  9. and TBCR Study Group
  1. 1Department of Orthopedic Surgery, Nagoya University School of Medicine, Nagoya
  2. 2Department of Rheumatology, Tokyo Koseinenkin Hospital, Tokyo, Japan


Background Biologics have molecular target such as cytokine and its receptor. It should be critical for maximizing its clinical response how biologics completely inhibit signalling of the target cytokines. However, it is difficult to know whether administered biologics inhibit the target molecules completely or not. Tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor. Interestingly, IL-6 directly stimulates the expression of C-reactive protein (CRP).

Objectives We studied clinical results of TCZ for 52 weeks based on normalization of CRP level during treatment, which could be a possible index of adequate dose of TCZ for each patient.

Methods All RA patients (n=122) who underwent TCZ treatment between May 2008 and September 2009 at Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communication Study Group) were enrolled in this study. Demographic data at baseline and the following parameters of disease activity (tender joint count (TJC) and swollen joint count (SJC) on 28 joints, patient global assessment (VAS), ESR, and serum CRP and MMP-3 levels during 52 weeks. We divided the patients into three groups based on the time of normalization of CRP levels (4 weeks; group A, N=78, 4-12 weeks; group B, N=28, positive CRP at 12 weeks; group C, N=16). We compared clinical results including remission rate at 52 weeks using the 2011 definition of remission (Boolean approach) as well as DAS28-ESR among these three groups.

Results Mean (SD) of age, disease duration and DAS28-ESR were 57 (13) years old, 10.5 (8.5) years and 5.8 (1.4),respectively. 61% of the patients had history of previous TNF-failure. 39% of the patients were treated with concomitant MTX. Patients in group C had higher disease activity (SJC, TJC, CRP, DAS28-ESR) than those in group A and B at baseline. We found that, at 52 weeks, patients in group A and B achieved significantly higher rate of DAS-remission (48.6%), SJC≤1, and TJC≤1 than those in group C (Fig.1 and 2). Especially, VAS as well as MMP-3 was significantly improved in patients in group A and B but not those in group C at all (Fig. 3). Patients in group A and B had more normal level of MMP-3 than those in group C. Multivariate logistic analysis including concomitant MTX, previous use of TNF inhibitor, disease duration, clearly showed lower CRP (cut-off, 2.13 mg/dl, determined by ROC analysis) was independent factor for achieve normal CRP level until 12 w.

Conclusions In this study, we clearly showed that patients with normalization of CRP level at 12 weeks, which could be related to adequate dose of TCZ for complete inhibition of IL-6 signalling for each patient, achieved better clinical results.

Disclosure of Interest T. Kojima Speakers Bureau: Abbott Japan, Chugai Pharmaceutical, Daiichi Sankyo Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Pfizer Japan, Takeda Pharmaceutical, K. Funahashi: None Declared, N. Takahashi: None Declared, D. Kato: None Declared, H. Matsubara: None Declared, Y. Hattori: None Declared, Y. Yabe: None Declared, N. Ishiguro Speakers Bureau: Abbott Japan, Chugai Pharmaceutical, Daiichi Sankyo Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Pfizer Japan, Takeda Pharmaceutical

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