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.