title: Monitoring C-reactive protein levels to predict favourable clinical outcomes from tocilizumab treatment in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Orthopaedic Surgery and Rheumatology, Nagoya University Hospital, Nagoya University School of Medicine, 65 Tsurumai, Showa, Nagoya, Japan, toshik@med.nagoya-u.ac.jp.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Kojima
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yabe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kaneko
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hirano
authors.forename: Hisato
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyake
authors.forename: Hideki
authors.initials: H
authors.lastname: Takagi
authors.forename: Takefumi
authors.initials: T
authors.lastname: Kato
authors.forename: Kenya
authors.initials: K
authors.lastname: Terabe
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Wanatabe
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Daihei
authors.initials: D
authors.lastname: Kida
authors.forename: Tomone
authors.initials: T
authors.lastname: Shioura
authors.forename: Koji
authors.initials: K
authors.lastname: Funahashi
authors.forename: Daizo
authors.initials: D
authors.lastname: Kato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsubara
authors.forename: Nobunori
authors.initials: N
authors.lastname: Takahashi
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Hattori
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Asai
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011379:Prognosis; D012042:Registries; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; C502936:tocilizumab; D008727:Methotrexate