title: Efficacy and safety of ascending methotrexate dose in combination with adalimumab: the randomised CONCERTO trial.
abstract: OBJECTIVE
  CONCERTO was a randomised, double-blind, parallel-armed study of methotrexate (MTX) in combination with adalimumab to assess whether an increasing trend of efficacy and decreased safety exists when increasing MTX dose in patients with early rheumatoid arthritis (RA).
  
  
  METHODS
  Early, biologic and MTX-naive RA patients (N=395) were evenly randomised to open-label adalimumab (40 mg every other week) plus weekly blinded 2.5, 5, 10 or 20 mg MTX for 26 weeks. Clinical, radiographic and functional outcomes were analysed using two-sided linear trend tests or one-way analysis of covariance.
  
  
  RESULTS
  Statistically significant increasing trends were observed in the proportion of patients achieving the primary endpoint, 28-joint count disease activity score with C reactive protein (DAS28(CRP)) <3.2 (42.9%, 44.0%, 56.6% and 60.2% for 2.5, 5, 10 or 20 mg/week MTX, respectively), DAS28(CRP) <2.6 and American College of Rheumatology 50/70/90 responses with increasing doses of MTX in combination with adalimumab. No statistical differences in minimal clinically important differences in physical function were detected. Statistically significant trends for achieving low disease activity and remission were demonstrated with increasing MTX dose by validated clinical indices; differences comparing 10 and 20 mg MTX were minimal. Adalimumab serum concentrations increased with ascending dose up to 10 mg MTX. More patients experienced infectious adverse events with increasing MTX dose.
  
  
  CONCLUSIONS
  Increasing doses of MTX in combination with adalimumab demonstrated a statistically significant trend in improved clinical outcomes that mimicked the adalimumab pharmacokinetic profile. In early RA patients initiating adalimumab combination therapy, efficacy of 10 and 20 mg/week MTX appeared equivalent.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Gerd-Rűdiger
authors.initials: GR
authors.lastname: Burmester
authors.affiliation: Altoona Center for Clinical Research, Duncansville, Pennsylvania, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Kivitz
authors.affiliation: AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kupper
authors.affiliation: AbbVie Inc, North Chicago, Illinois, USA.
authors.forename: Udayasankar
authors.initials: U
authors.lastname: Arulmani
authors.affiliation: AbbVie, Rungis, France.
authors.forename: Stefan
authors.initials: S
authors.lastname: Florentinus
authors.affiliation: AbbVie Inc, North Chicago, Illinois, USA.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Goss
authors.affiliation: AbbVie Inc, North Chicago, Illinois, USA.
authors.forename: Suchitrita S
authors.initials: SS
authors.lastname: Rathmann
authors.affiliation: University of Texas Southwestern, Dallas, Texas, USA.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Fleischmann
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D000068879:Adalimumab; D008727:Methotrexate