title: Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study.
abstract: OBJECTIVE
  To assess the efficacy and safety of certolizumab pegol (CZP)+dose-optimised methotrexate (MTX) versus placebo (PBO)+dose-optimised MTX in inducing and sustaining clinical remission in DMARD-naïve patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks.
  
  
  METHODS
  DMARD-naïve patients with ≤1 year of active RA were randomised (3:1) in a double-blind manner to CZP (400 mg Weeks 0, 2, 4, then 200 mg Q2W to Week 52)+MTX or PBO+MTX (the mean optimised-MTX dose=21 and 22 mg/week, respectively). Sustained remission (sREM) and sustained low disease activity (sLDA; DAS28(ESR)<2.6 and DAS28(ESR)≤3.2, respectively, at both Weeks 40 and 52) were the primary and secondary endpoints.
  
  
  RESULTS
  Patients were randomised to CZP+MTX (n=660) and PBO+MTX (n=219). At Week 52, significantly more patients assigned to CZP+MTX compared with PBO+MTX achieved sREM (28.9% vs 15.0%, p<0.001) and sLDA (43.8% vs 28.6%, p<0.001). Inhibition of radiographic progression and improvements in physical functioning were significantly greater for CZP+MTX versus PBO+MTX (van der Heijde modified total Sharp score (mTSS) mean absolute change from baseline (CFB): 0.2 vs 1.8, p<0.001, rate of mTSS non-progressors: 70.3% vs 49.7%, p<0.001; least squares (LS) mean CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI): -1.00 vs -0.82, p<0.001). Incidence of adverse events (AEs) and serious AEs was similar between treatment groups. Infection was the most frequent AE, with higher incidence for CZP+MTX (71.8/100 patient-years (PY)) versus PBO+MTX (52.7/100 PY); the rate of serious infection was similar between CZP+MTX (3.3/100 PY) and PBO+MTX (3.7/100 PY).
  
  
  CONCLUSIONS
  CZP+dose-optimised MTX treatment of DMARD-naïve early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX.
  
  
  BACKGROUND
  NCT01519791.
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.|NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: P
authors.initials: P
authors.lastname: Emery
authors.affiliation: Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: C O
authors.initials: CO
authors.lastname: Bingham
authors.affiliation: Rheumatology and Clinical Immunology, Charité-University Medicine, Berlin, Germany.
authors.forename: G R
authors.initials: GR
authors.lastname: Burmester
authors.affiliation: Division of Rheumatology, Weill Cornell Medical College, Hospital for Special Surgery, New York, New York, USA.
authors.forename: V P
authors.initials: VP
authors.lastname: Bykerk
authors.affiliation: Division of Rheumatology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Furst
authors.affiliation: Université Paris-Sud, Hôpitaux Universitaires Paris-Sud, AP-HP, Le Kremlin Bicêtre, France.
authors.forename: X
authors.initials: X
authors.lastname: Mariette
authors.affiliation: Deprtment of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: D
authors.identifier: http://orcid.org/0000-0002-5781-158X
authors.initials: D
authors.lastname: van der Heijde
authors.affiliation: Unit for Clinical Therapy Research, Inflammatory Disease, Karolinska Institute, Stockholm, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: van Vollenhoven
authors.affiliation: UCB Pharma, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Arendt
authors.affiliation: UCB Pharma, Brussels, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Mountian
authors.affiliation: UCB Pharma, Brussels, Belgium.
authors.forename: O
authors.initials: O
authors.lastname: Purcaru
authors.affiliation: UCB Pharma, Raleigh, North Carolina, USA.
authors.forename: D
authors.initials: D
authors.lastname: Tatla
authors.forename: B
authors.initials: B
authors.lastname: VanLunen
authors.affiliation: UCB Pharma, Raleigh, North Carolina, USA.|Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Weinblatt
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000068582:Certolizumab Pegol / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D007239:Infections / Q000139:chemically induced; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011379:Prognosis; D011859:Radiography; D012074:Remission Induction
chemical_list: D018501:Antirheumatic Agents; D000068582:Certolizumab Pegol; D008727:Methotrexate
keywords: Anti-TNF; DMARDs (biologic); Early Rheumatoid Arthritis; Methotrexate