title: The effect of disease modifying therapies on brain atrophy in patients with relapsing-remitting multiple sclerosis: a systematic review and meta-analysis.
abstract: BACKGROUND
  The aim of the present meta-analysis was to evaluate the effect of disease-modifying drugs (DMD) on brain atrophy in patients with relapsing-remitting multiple sclerosis (RRMS) using available randomized-controlled trial (RCT) data.
  
  
  METHODS
  We conducted a systematic review and meta-analysis according to PRISMA guidelines of all available RCTs of patients with RRMS that reported data on brain volume measurements during the study period.
  
  
  RESULTS
  We identified 4 eligible studies, including a total of 1819 RRMS patients (71% women, mean age 36.5 years, mean baseline EDSS-score: 2.4). The mean percentage change in brain volume was found to be significantly lower in DMD versus placebo subgroup (standardized mean difference: -0.19; 95%CI: -0.27--0.11; p<0.001). We detected no evidence of heterogeneity between estimates (I2 = 30%, p = 0.19) nor publication bias in the Funnel plots. Sensitivity analyses stratifying studies according to brain atrophy neuroimaging protocol disclosed no evidence of heterogeneity (p = 0.16). In meta-regression analyses, the percentage change in brain volume was found to be inversely related with duration of observation period in both DMD (meta-regression slope = -0.03; 95% CI: -0.04--0.02; p<0.001) and placebo subgroups (meta-regression slope = -0.05; 95% CI: -0.06--0.04; p<0.001). However, the rate of percentage brain volume loss over time was greater in placebo than in DMD subgroup (p = 0.017, ANCOVA).
  
  
  CONCLUSIONS
  DMD appear to be effective in attenuating brain atrophy in comparison to placebo and their benefit in delaying the rate of brain volume loss increases linearly with longer treatment duration.
authors.affiliation: Second Department of Neurology, "Attikon" Hospital, School of Medicine, University of Athens, Athens, Greece; Department of Neurology, The University of Tennessee Health Science Center, Memphis, Tennessee, United States of America; International Clinical Research Center, Department of Neurology, St. Anne's University Hospital in Brno, Brno, Czech Republic.
authors.forename: Georgios
authors.initials: G
authors.lastname: Tsivgoulis
authors.affiliation: Second Department of Neurology, "Attikon" Hospital, School of Medicine, University of Athens, Athens, Greece; Department of Neurology, School of Medicine, University of Ioannina, Ioannina, Greece.
authors.forename: Aristeidis H
authors.initials: AH
authors.lastname: Katsanos
authors.affiliation: Second Department of Neurology, "AHEPA" University Hospital, Aristotelion University of Thessaloniki, Thessaloniki, Macedonia, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Grigoriadis
authors.affiliation: Department of Neurology, University Hospital of Larissa, University of Thessaly, Larissa, Greece.
authors.forename: Georgios M
authors.initials: GM
authors.lastname: Hadjigeorgiou
authors.affiliation: Department of Neurology, Alexandroupolis University Hospital, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Heliopoulos
authors.affiliation: First Department of Neurology, "Eginition" Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Kilidireas
authors.affiliation: Second Department of Neurology, "Attikon" Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Voumvourakis
mesh_terms: D001284:Atrophy / Q000517:prevention & control; D001921:Brain / Q000473:pathology*; D006801:Humans; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents