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The effect of disease modifying therapies on brain atrophy in patients with relapsing-remitting multiple sclerosis: a systematic review and meta-analysis.

Tsivgoulis G, Katsanos AH, Grigoriadis N, Hadjigeorgiou GM, Heliopoulos I, Kilidireas C, Voumvourakis K - PLoS ONE (2015)

Bottom Line: 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).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).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.

View Article: PubMed Central - PubMed

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.

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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Related in: MedlinePlus

Flow chart presenting the selection of eligible studies.
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pone.0116511.g001: Flow chart presenting the selection of eligible studies.

Mentions: Systematic search of MEDLINE and SCOPUS databases yielded 60 and 57 results respectively. Subsequent search in the CENTRAL Register of Controlled Trials retrieved no additional RCTs. After removing duplicates, the titles and abstracts from the remaining 75 studies were screened and 17 potentially eligible studies for the meta-analysis were retained. After retrieving the full-text version of the aforementioned 17 studies, 4 studies were excluded because they did not include a placebo subgroup and 2 studies because they were not RCT (cohort studies), 6 studies because they reported the brain volume changes in median values and 1 study because it did not report the SDs or other measures of dispersion (Table A in S1 File). In the final presentation of the literature search results, there was no conflict or disagreement between the 2 reviewers and the 4 studies that met the study protocol’s inclusion criteria (IMPROVE [7], FREEDOMS [8], E/C GASG [9], MSCRG [10]) were included both in the qualitative and quantitative synthesis (Fig. 1). The characteristics of the included studies, comprising 1819 patients (71% women, mean age: 36.5 years, mean baseline EDSS score: 2.4) are summarized in Table 1.


The effect of disease modifying therapies on brain atrophy in patients with relapsing-remitting multiple sclerosis: a systematic review and meta-analysis.

Tsivgoulis G, Katsanos AH, Grigoriadis N, Hadjigeorgiou GM, Heliopoulos I, Kilidireas C, Voumvourakis K - PLoS ONE (2015)

Flow chart presenting the selection of eligible studies.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4355592&req=5

pone.0116511.g001: Flow chart presenting the selection of eligible studies.
Mentions: Systematic search of MEDLINE and SCOPUS databases yielded 60 and 57 results respectively. Subsequent search in the CENTRAL Register of Controlled Trials retrieved no additional RCTs. After removing duplicates, the titles and abstracts from the remaining 75 studies were screened and 17 potentially eligible studies for the meta-analysis were retained. After retrieving the full-text version of the aforementioned 17 studies, 4 studies were excluded because they did not include a placebo subgroup and 2 studies because they were not RCT (cohort studies), 6 studies because they reported the brain volume changes in median values and 1 study because it did not report the SDs or other measures of dispersion (Table A in S1 File). In the final presentation of the literature search results, there was no conflict or disagreement between the 2 reviewers and the 4 studies that met the study protocol’s inclusion criteria (IMPROVE [7], FREEDOMS [8], E/C GASG [9], MSCRG [10]) were included both in the qualitative and quantitative synthesis (Fig. 1). The characteristics of the included studies, comprising 1819 patients (71% women, mean age: 36.5 years, mean baseline EDSS score: 2.4) are summarized in Table 1.

Bottom Line: 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).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).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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus