Original Article

Modern Rheumatology

, Volume 23, Issue 5, pp 977-985

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

  • Toshihisa KojimaAffiliated withDepartment of Orthopaedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University School of Medicine Email author 
  • , Yuichiro YabeAffiliated withDepartment of Rheumatology, Tokyo Kosei Nenkin Hospital
  • , Atsushi KanekoAffiliated withDepartment of Orthopaedic Surgery, Nagoya Medical Centre
  • , Yuji HiranoAffiliated withDepartment of Rheumatology, Toyohashi Municipal Hospital
  • , Hisato IshikawaAffiliated withDepartment of Orthopaedic Surgery, Nagoya Medical Centre
  • , Masatoshi HayashiAffiliated withDepartment of Rheumatology, Nagano Red Cross Hospital
  • , Hiroyuki MiyakeAffiliated withDepartment of Orthopaedic Surgery, Ichinomiya Municipal Hospital
  • , Hideki TakagiAffiliated withDepartment of Orthopaedic Surgery, Nagoya Kyoritsu Hospital
  • , Takefumi KatoAffiliated withKato Orthopaedic Clinic
    • , Kenya TerabeAffiliated withDepartment of Orthopaedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University School of MedicineDepartment of Orthopaedic Surgery, Fukuroi Municipal Hospital
    • , Tsuyoshi WanatabeAffiliated withDepartment of Orthopaedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University School of MedicineDepartment of Orthopaedic Surgery, Kariya-Toyota General Hospital
    • , Hiroki TsuchiyaAffiliated withDepartment of Orthopaedic Surgery, Nagoya Kyoritsu Hospital
    • , Daihei KidaAffiliated withDepartment of Orthopaedic Surgery, Nagoya Medical Centre
    • , Tomone ShiouraAffiliated withDepartment of Orthopaedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University School of MedicineDepartment of Orthopaedic Surgery, Shizuoka Kosei Hospital
    • , Koji FunahashiAffiliated withDepartment of Orthopaedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University School of Medicine
    • , Daizo KatoAffiliated withDepartment of Orthopaedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University School of Medicine
    • , Hiroyuki MatsubaraAffiliated withDepartment of Orthopaedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University School of Medicine
    • , Nobunori TakahashiAffiliated withDepartment of Orthopaedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University School of Medicine
    • , Yosuke HattoriAffiliated withDepartment of Orthopaedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University School of Medicine
    • , Nobuyuki AsaiAffiliated withDepartment of Orthopaedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University School of MedicineDepartment of Orthopaedic Surgery, Nagoya University, Faculty and Graduate School of Medicine
    • , Naoki IshiguroAffiliated withDepartment of Orthopaedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University School of MedicineDepartment of Orthopaedic Surgery, Nagoya University, Faculty and Graduate School of Medicine

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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