title: Interferons in relapsing remitting multiple sclerosis: a systematic review.
abstract: BACKGROUND
  Recombinant interferons have been approved by many national regulatory agencies for treatment of relapsing remitting multiple sclerosis, but widespread discussion continues about their true effectiveness, benefits, side-effects, and costs.
  
  
  METHODS
  With the Cochrane Collaboration methodology, we reviewed all published, randomised, placebo-controlled trials of recombinant interferons undertaken in patients with relapsing remitting multiple sclerosis between 1993 and 2002. Our primary aim was to find out whether recombinant interferons reduced the number of patients who had clinical exacerbations and disease progression, compared with placebo.
  
  
  RESULTS
  The seven trials that met our criteria included 1215 randomised patients: data from 667 (55%) were available for analysis at 1 year's and from 919 (76%) at 2 years' follow-up. Interferon seemed to reduce the number of patients who had exacerbations during the first year of treatment (relative risk 0.73, 95% CI 0.54-0.99), but results at 2 years' follow-up were not robust and were difficult to interpret because of the many dropouts. Although the number of patients who had exacerbations (0.81, 0.74-0.89) or progressed (0.70, 0.55-0.88) during the first 2 years fell significantly in the protocol analysis, results were inconclusive after sensitivity analyses for exacerbations (1.11, 0.73-1.68) and disease progression (1.31, 0.60-2.89). Data were insufficient to establish whether steroid use and admissions to hospital were reduced in the interferon group. Similarly, MRI outcome data could not be analysed quantitatively. Side-effects were common, and acute toxic effects adversely affected quality of life.
  
  
  CONCLUSIONS
  Recombinant interferons slightly reduce the number of patients who have exacerbations during first year of treatment. Their clinical effect beyond 1 year is uncertain and new trials are needed to assess their long-term effectiveness and side-effects.
authors.affiliation: Unità di Neuroepidemiologia, Istituto Nazionale Neurologico C Besta, Milan, Italy. gfilippini@istituto-besta.it
authors.forename: Graziella
authors.initials: G
authors.lastname: Filippini
authors.forename: Luca
authors.initials: L
authors.lastname: Munari
authors.forename: Barbara
authors.initials: B
authors.lastname: Incorvaia
authors.forename: George C
authors.initials: GC
authors.lastname: Ebers
authors.forename: Chris
authors.initials: C
authors.lastname: Polman
authors.forename: Roberto
authors.initials: R
authors.lastname: D'Amico
authors.forename: George P A
authors.initials: GP
authors.lastname: Rice
mesh_terms: D000328:Adult; D006801:Humans; D007372:Interferons / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D007372:Interferons