title: Certolizumab pegol plus methotrexate is significantly more effective than placebo plus methotrexate in active rheumatoid arthritis: findings of a fifty-two-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of 2 dosage regimens of lyophilized certolizumab pegol (a novel PEGylated anti-tumor necrosis factor agent) as adjunctive therapy to methotrexate (MTX) in patients with active rheumatoid arthritis (RA) with an inadequate response to MTX therapy alone.
  
  
  METHODS
  In this 52-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, 982 patients were randomized 2:2:1 to receive treatment with subcutaneous certolizumab pegol at an initial dosage of 400 mg given at weeks 0, 2, and 4, with a subsequent dosage of 200 mg or 400 mg given every 2 weeks, plus MTX, or placebo plus MTX. Co-primary end points were the response rate at week 24 according to the American College of Rheumatology 20% criteria for improvement (ACR20) and the mean change from baseline in the modified total Sharp score at week 52.
  
  
  RESULTS
  At week 24, ACR20 response rates using nonresponder imputation for the certolizumab pegol 200-mg and 400-mg groups were 58.8% and 60.8%, respectively, as compared with 13.6% for the placebo group. Differences in ACR20 response rates versus placebo were significant at week 1 and were sustained to week 52 (P < 0.001). At week 52, mean radiographic progression from baseline was reduced in patients treated with certolizumab pegol 200 mg (0.4 Sharp units) or 400 mg (0.2 Sharp units) as compared with that in placebo-treated patients (2.8 Sharp units) (P < 0.001 by rank analysis). Improvements in all ACR core set of disease activity measures, including physical function, were observed by week 1 with both certolizumab pegol dosage regimens. Most adverse events were mild or moderate.
  
  
  CONCLUSIONS
  Treatment with certolizumab pegol 200 or 400 mg plus MTX resulted in a rapid and sustained reduction in RA signs and symptoms, inhibited the progression of structural joint damage, and improved physical function as compared with placebo plus MTX treatment in RA patients with an incomplete response to MTX.
authors.affiliation: University of Toronto, Toronto, Ontario, Canada. edkeystone@mtsinai.on.ca
authors.forename: Edward
authors.initials: E
authors.lastname: Keystone
authors.forename: Désireé van der
authors.initials: Dv
authors.lastname: Heijde
authors.forename: David
authors.initials: D
authors.lastname: Mason
authors.forename: Robert
authors.initials: R
authors.lastname: Landewé
authors.forename: Ronald Van
authors.initials: RV
authors.lastname: Vollenhoven
authors.forename: Bernard
authors.initials: B
authors.lastname: Combe
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.forename: Vibeke
authors.initials: V
authors.lastname: Strand
authors.forename: Philip
authors.initials: P
authors.lastname: Mease
authors.forename: Chintu
authors.initials: C
authors.lastname: Desai
authors.forename: Karel
authors.initials: K
authors.lastname: Pavelka
mesh_terms: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D000068582:Certolizumab Pegol; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011859:Radiography
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007140:Immunoglobulin Fab Fragments; D011092:Polyethylene Glycols; D000068582:Certolizumab Pegol; D008727:Methotrexate