title: The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression.
abstract: OBJECTIVE
  To evaluate efficacy and safety of combination therapy using certolizumab pegol (CZP) and methotrexate (MTX) as first-line treatment for MTX-naive, early rheumatoid arthritis (RA) with poor prognostic factors, compared with MTX alone.
  
  
  METHODS
  MTX-naive, early RA patients with ≤12 months persistent disease, high anti-cyclic citrullinated peptide, and either rheumatoid factor positive and/or presence of bone erosions were enrolled in this multicentre, double-blind, randomised placebo (PBO)-controlled study. Patients were randomised 1:1 to CZP+MTX or PBO+MTX for 52 weeks. Primary endpoint was inhibition of radiographic progression (change from baseline in modified Total Sharp Score (mTSS CFB)) at week 52. Secondary endpoints were mTSS CFB at week 24, and clinical remission rates at weeks 24 and 52.
  
  
  RESULTS
  316 patients randomised to CZP+MTX (n=159) or PBO+MTX (n=157) had comparable baseline characteristics reflecting features of early RA (mean disease duration: 4.0 vs 4.3 months; Disease Activity Score 28-joint assessment (DAS28)) (erythrocyte sedimentation rate (ESR)): 5.4 vs 5.5; mTSS: 5.2 vs 6.0). CZP+MTX group showed significantly greater inhibition of radiographic progression relative to PBO+MTX at week 52 (mTSS CFB=0.36 vs 1.58; p<0.001) and week 24 (mTSS CFB=0.26 vs 0.86; p=0.003). Clinical remission rates (Simple Disease Activity Index, Boolean and DAS28 (ESR)) of the CZP+MTX group were significantly higher compared with those of the PBO+MTX group, at weeks 24 and 52. Safety results in both groups were similar, with no new safety signals observed with addition of CZP to MTX.
  
  
  CONCLUSIONS
  In MTX-naive early RA patients with poor prognostic factors, CZP+MTX significantly inhibited structural damage and reduced RA signs and symptoms, demonstrating the efficacy of CZP in these patients.
  
  
  BACKGROUND
  (NCT01451203).
authors.affiliation: Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
authors.affiliation: The University of Tokyo, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.affiliation: Faculty of Medicine, Nagoya University Graduate School, Nagoya, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishiguro
authors.affiliation: University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Sasebo Chuo Hospital, Nagasaki, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
authors.affiliation: Tohoku University, Sendai, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: University of Toyama School of Medicine, Toyama, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Origasa
authors.affiliation: Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Yasuda
authors.affiliation: Hiroshima Rheumatology Clinic, Hiroshima, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamanishi
authors.affiliation: Yokohama Rosai Hospital, Yokohama, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kita
authors.affiliation: Matsubara Mayflower Hospital, Kato, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Matsubara
authors.affiliation: Jichi Medical University, Tochigi, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwamoto
authors.affiliation: UCB Pharma, Tokyo, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Shoji
authors.affiliation: Astellas Pharma Inc., Tokyo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Okada
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Désirée
authors.identifier: http://orcid.org/0000-0002-5781-158X
authors.initials: D
authors.lastname: van der Heijde
authors.affiliation: Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
authors.affiliation: Hokkaido University Graduate School of Medicine, Sapporo, Japan NTT Sapporo Medical Centre, Sapporo, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001799:Blood Sedimentation; D000068582:Certolizumab Pegol / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D011379:Prognosis; D011859:Radiography; D012074:Remission Induction; D012217:Rheumatoid Factor / Q000097:blood; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D018501:Antirheumatic Agents; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor; D000068582:Certolizumab Pegol; D008727:Methotrexate
keywords: Anti-TNF; Disease Activity; Early Rheumatoid Arthritis; Inflammation; Rheumatoid Arthritis