The effect of disease modifying therapies on brain atrophy in patients with relapsing-remitting multiple sclerosis

A systematic review and meta-analysis

Georgios Tsivgoulis, Aristeidis H. Katsanos, Nikolaos Grigoriadis, Georgios M. Hadjigeorgiou, Ioannis Heliopoulos, Constantinos Kilidireas, Konstantinos Voumvourakis

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0116511
JournalPLoS One
Volume10
Issue number3
DOIs
StatePublished - Mar 1 2015

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Relapsing-Remitting Multiple Sclerosis
systematic review
sclerosis
atrophy
meta-analysis
Atrophy
Meta-Analysis
Brain
brain
therapeutics
placebos
drugs
Placebos
Pharmaceutical Preparations
Therapeutics
Neuroimaging
Volume measurement
Publication Bias
duration
Randomized Controlled Trials

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

The effect of disease modifying therapies on brain atrophy in patients with relapsing-remitting multiple sclerosis : A systematic review and meta-analysis. / Tsivgoulis, Georgios; Katsanos, Aristeidis H.; Grigoriadis, Nikolaos; Hadjigeorgiou, Georgios M.; Heliopoulos, Ioannis; Kilidireas, Constantinos; Voumvourakis, Konstantinos.

In: PLoS One, Vol. 10, No. 3, e0116511, 01.03.2015.

Research output: Contribution to journalArticle

Tsivgoulis, Georgios ; Katsanos, Aristeidis H. ; Grigoriadis, Nikolaos ; Hadjigeorgiou, Georgios M. ; Heliopoulos, Ioannis ; Kilidireas, Constantinos ; Voumvourakis, Konstantinos. / The effect of disease modifying therapies on brain atrophy in patients with relapsing-remitting multiple sclerosis : A systematic review and meta-analysis. In: PLoS One. 2015 ; Vol. 10, No. 3.
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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.",
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AB - 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.

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