Vol.23 No.5

Original Article

Monitoring C-reactive protein levels to predict favourable clinical outcomes from tocilizumab treatment in patients with rheumatoid arthritis

Authors

Toshihisa Kojima1 , Yuichiro Yabe2 , Atsushi Kaneko3 , Yuji Hirano4 , Hisato Ishikawa3 , Masatoshi Hayashi5 , Hiroyuki Miyake6 , Hideki Takagi7 , Takefumi Kato8 , Kenya Terabe1, 9 , Tsuyoshi Wanatabe10 , Hiroki Tsuchiya7

  • Department of Orthopaedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University School of Medicine, 65 Tsurumai, Showa, Nagoya, Japan
  • Department of Rheumatology, Tokyo Kosei Nenkin Hospital, Tokyo, Japan
  • Department of Orthopaedic Surgery, Nagoya Medical Centre, Nagoya, Japan
  • Department of Rheumatology, Toyohashi Municipal Hospital, Toyohashi, Japan
  • Department of Rheumatology, Nagano Red Cross Hospital, Nagano, Japan
  • Department of Orthopaedic Surgery, Ichinomiya Municipal Hospital, Ichinomiya, Japan
  • Department of Orthopaedic Surgery, Nagoya Kyoritsu Hospital, Nagoya, Japan
  • Kato Orthopaedic Clinic, Okazaki, Japan
  • Department of Orthopaedic Surgery, Fukuroi Municipal Hospital, Fukuroi, Japan
  • Department of Orthopaedic Surgery, Kariya-Toyota General Hospital, Kariya, Japan
  • Department of Orthopaedic Surgery, Shizuoka Kosei Hospital, Shizuoka, Japan
  • Department of Orthopaedic Surgery, Nagoya University, Faculty and Graduate School of Medicine, Nagoya, Japan
Received:

3 July 2012

Accepted:

4 October 2012

Published online:

26 October 2012

Full Text

PDF　(member's only)

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 proportionalhazards
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.

Key words

Rheumatoid arthritis, Tocilizumab, C-reactive protein, Interleukin-6