title: A multicentre, randomised, double blind, placebo controlled phase II study of subcutaneous interferon beta-1a in the treatment of patients with active rheumatoid arthritis.
abstract: OBJECTIVE
  To assess the efficacy of interferon beta (IFN beta) in combination with methotrexate in treatment of patients with rheumatoid arthritis.
  
  
  METHODS
  209 patients with active rheumatoid arthritis, who had been on methotrexate for at least six months and at a stable dose for four weeks before study entry, were randomised in double blind fashion to receive placebo (0.05 ml or 0.5 ml), IFN beta 2.2 microg (0.05 ml), or IFN beta 44 microg (0.5 ml), given subcutaneously three times weekly for 24 weeks. The primary efficacy measure was a change in radiological scores at week 24. The secondary endpoint was the proportion of patients who met the ACR 20% improvement criteria at the end of the study. Synovial biopsy specimens were obtained before and after treatment from a subset of patients. Immunohistochemistry was used to detect the presence of inflammatory cells and the results were measured by digital image analysis. Collagen crosslinks were measured in urine at different times throughout the study.
  
  
  RESULTS
  Analysis of radiological scores and clinical variable showed no changes in any of the groups, and there were no differences between the groups. On microscopic analysis of synovial tissue there was no significant change in the scores for infiltration by inflammatory cells after IFN beta treatment. Urinary levels of collagen crosslinks were unchanged between the treatment groups.
  
  
  CONCLUSIONS
  At the doses tested, treatment with IFN beta three times weekly in combination with methotrexate did not have a clinical or radiological effect in patients with rheumatoid arthritis.
authors.affiliation: Academic Medical Centre, University of Amsterdam, Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van Holten
authors.forename: K
authors.initials: K
authors.lastname: Pavelka
authors.forename: J
authors.initials: J
authors.lastname: Vencovsky
authors.forename: H
authors.initials: H
authors.lastname: Stahl
authors.forename: B
authors.initials: B
authors.lastname: Rozman
authors.forename: M
authors.initials: M
authors.lastname: Genovese
authors.forename: A J
authors.initials: AJ
authors.lastname: Kivitz
authors.forename: J
authors.initials: J
authors.lastname: Alvaro
authors.forename: G
authors.initials: G
authors.lastname: Nuki
authors.forename: D E
authors.initials: DE
authors.lastname: Furst
authors.forename: G
authors.initials: G
authors.lastname: Herrero-Beaumont
authors.forename: I B
authors.initials: IB
authors.lastname: McInnes
authors.forename: P
authors.initials: P
authors.lastname: Musikic
authors.forename: P P
authors.initials: PP
authors.lastname: Tak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011859:Radiography; D013583:Synovial Membrane / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D016899:Interferon-beta; D000068556:Interferon beta-1a; D008727:Methotrexate