title: Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and tumour necrosis factor blockade.
abstract: OBJECTIVE
  To examine the association of radiographic progression and disease activity states in patients with rheumatoid arthritis (RA) treated with methotrexate with or without infliximab.
  
  
  METHODS
  Patients (n = 1049) with active RA for 3 years or less and no previous methotrexate treatment were randomly assigned (4 : 5 : 5) to receive methotrexate plus placebo or methotrexate plus infliximab 3 or 6 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter to week 46. Disease activity was classified by the simplified disease activity index as remission (< or =3.3), low (>3.3 to < or =11), moderate (>11 to < or =26), high (>26). Radiographic progression was measured as a change from baseline to week 54 in total Sharp score.
  
  
  RESULTS
  At weeks 14 and 54, more patients receiving methotrexate plus infliximab than methotrexate plus placebo were in remission (10.7% versus 2.8% week 14; 21.3% versus 12.3% week 54; p<0.001 for both). Methotrexate plus placebo halted radiographic progression only if patients achieved remission within 3 months, whereas methotrexate plus infliximab also halted or minimised progression in patients with low or moderate activity, respectively. Patients with persistently high disease activity levels had much less progression of joint damage if treated with methotrexate plus infliximab versus methotrexate monotherapy. Even with infliximab plus methotrexate there was a direct relationship between disease activity and radiographic changes, although the slope was deflected when compared with methotrexate monotherapy.
  
  
  CONCLUSIONS
  With methotrexate, joint damage progresses even at low and moderate disease activity levels, whereas methotrexate plus infliximab inhibits radiographic progression across all disease activity states.
authors.affiliation: Department of Internal Medicine III, Medical University of Vienna, Austria. josef.smolen@wienkav.at
authors.forename: J S
authors.initials: JS
authors.lastname: Smolen
authors.forename: C
authors.initials: C
authors.lastname: Han
authors.forename: D M F M
authors.initials: DM
authors.lastname: van der Heijde
authors.forename: P
authors.initials: P
authors.lastname: Emery
authors.forename: J M
authors.initials: JM
authors.lastname: Bathon
authors.forename: E
authors.initials: E
authors.lastname: Keystone
authors.forename: R N
authors.initials: RN
authors.lastname: Maini
authors.forename: J R
authors.initials: JR
authors.lastname: Kalden
authors.forename: D
authors.initials: D
authors.lastname: Aletaha
authors.forename: D
authors.initials: D
authors.lastname: Baker
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.forename: M
authors.initials: M
authors.lastname: Bala
authors.forename: E W
authors.initials: EW
authors.lastname: St Clair
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000276:immunology; D001175:Arthrography; D018450:Disease Progression; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D012074:Remission Induction; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D008727:Methotrexate