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Monitoring C-reactive protein levels to predict favourable clinical outcomes from tocilizumab treatment in patients with rheumatoid arthritis
Authors:Toshihisa Kojima  Yuichiro Yabe  Atsushi Kaneko  Yuji Hirano  Hisato Ishikawa  Masatoshi Hayashi  Hiroyuki Miyake  Hideki Takagi  Takefumi Kato  Kenya Terabe  Tsuyoshi Wanatabe  Hiroki Tsuchiya  Daihei Kida  Tomone Shioura  Koji Funahashi  Daizo Kato  Hiroyuki Matsubara  Nobunori Takahashi  Yosuke Hattori  Nobuyuki Asai  Naoki Ishiguro
Affiliation:1. Department of Orthopaedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University School of Medicine, 65 Tsurumai, Showa, Nagoya, Japan
2. Department of Rheumatology, Tokyo Kosei Nenkin Hospital, Tokyo, Japan
3. Department of Orthopaedic Surgery, Nagoya Medical Centre, Nagoya, Japan
4. Department of Rheumatology, Toyohashi Municipal Hospital, Toyohashi, Japan
5. Department of Rheumatology, Nagano Red Cross Hospital, Nagano, Japan
6. Department of Orthopaedic Surgery, Ichinomiya Municipal Hospital, Ichinomiya, Japan
7. Department of Orthopaedic Surgery, Nagoya Kyoritsu Hospital, Nagoya, Japan
8. Kato Orthopaedic Clinic, Okazaki, Japan
9. Department of Orthopaedic Surgery, Fukuroi Municipal Hospital, Fukuroi, Japan
10. Department of Orthopaedic Surgery, Kariya-Toyota General Hospital, Kariya, Japan
11. Department of Orthopaedic Surgery, Shizuoka Kosei Hospital, Shizuoka, Japan
12. Department of Orthopaedic Surgery, Nagoya University, Faculty and Graduate School of Medicine, Nagoya, Japan
Abstract:

Objectives

The inflammatory cytokine interleukin-6 (IL-6) directly stimulates C-reactive protein (CRP) expression. The present study aimed to examine how clinical treatment outcomes of rheumatoid arthritis (RA) with tocilizumab (TCZ), a humanised monoclonal anti-IL-6 receptor antibody, are related to CRP levels monitored for 52 weeks.

Methods

One hundred and twenty-two RA patients who underwent TCZ treatment between May 2008 and September 2009 were registered in the Tsurumai Biologics Communication Registry. Data were collected at initiation of treatment (baseline) and over 52 weeks for Disease Activity Score 28-ESR (DAS28-ESR), Boolean core measurements, serum CRP levels and matrix metalloproteinase-3 levels. To compare clinical results, patients were divided into three groups based on treatment time required to achieve normal CRP levels.

Results

Multivariate analysis using the Cox proportional-hazards regression model found that higher CRP levels at baseline was a significant and independent factor in predicting normal CRP levels over 52 weeks (hazard ratio 0.86 per 1 mg/dL). In contrast, disease duration, concomitant methotrexate use and previous tumour necrosis factor inhibitor failure were not significant factors. Patients with normal CRP levels at 12 weeks of TCZ treatment achieved better clinical outcomes, including remission based on DAS28-ESR criteria, compared to patients with elevated CRP levels at 12 weeks.

Conclusions

Adequate suppression of pathological IL-6 signalling during TCZ treatment improves clinical outcomes and can be monitored with serum CRP levels, a readily available biomarker in clinical practice.
Keywords:Rheumatoid arthritis  Tocilizumab  C-reactive protein  Interleukin-6
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