title: Long-term impact of interferon or Glatiramer acetate in multiple sclerosis: A systematic review and meta-analysis.
abstract: BACKGROUND
  In recent years the impact of disease-modifying drugs on long-term progression in multiple sclerosis (MS) was assessed both in observational studies and in extension of randomized controlled trial (RCT). Aim of this work was to quantitatively summarize by a meta-analysis the long-term impact of immunomodulatory drugs (Interferon-Beta (IFN-β) or Glatiramer Acetate (GA)) in relapsing-remitting (RR) MS patients.
  
  
  METHODS
  We collected all published observational studies reporting the long-term efficacy of IFN-β or GA in RRMS patients. The primary outcome was the treatment effect on progression to a sustained EDSS score of 6 or to the Secondary Progressive (SP) phase. A non-parametric approach was adopted to test the overall treatment effect significance, while a random effect model was used to obtain a pooled quantitative estimate of the treatment benefit, in terms of hazard-ratios (HR) or Relative Risks, with their 95% confidence interval (CI).
  
  
  RESULTS
  Fourteen studies, on a total of 13,238 RRMS patients, were included in the meta-analysis. All studies but two reported a consistent effect of immunomodulatory treatment on long-term disease progression; the pooled effect on progression to EDSS 6 or SP was significant (p<0.01) when tested by the non-parametric test. The quantitative estimate of the treatment effect in reducing progression to EDSS 6 in the subset of studies reporting this outcome was HRpooled=0.49 (95% CI: 0.34-0.69), p<0.001.
  
  
  CONCLUSIONS
  Treatment with immunomodulators seems to reduce long-term probability of disability progression. Additional well-designed observational studies could help to confirm these findings.
authors.affiliation: Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Signori
authors.affiliation: Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Gallo
authors.affiliation: Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bovis
authors.affiliation: Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Nicolò
authors.initials: N
authors.lastname: Di Tullio
authors.affiliation: Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Maietta
authors.affiliation: Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy. Electronic address: mariapia.sormani@unige.it.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
mesh_terms: D000068717:Glatiramer Acetate / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007372:Interferons / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy*; D064887:Observational Studies as Topic
chemical_list: D007155:Immunologic Factors; D000068717:Glatiramer Acetate; D007372:Interferons
keywords: Disability progression; Interferon-beta; Long-term; Meta-analysis; Observational studies; Treatment effect