Cargando…

The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis

BACKGROUND: The quantification of brain atrophy in relapsing-remitting multiple sclerosis (RRMS) may serve as a marker of disease progression and treatment response. We compared the association between first-line (FL) or second-line (SL) disease-modifying drugs (DMDs) and brain volume changes over t...

Descripción completa

Detalles Bibliográficos
Autores principales: Branger, Pierre, Parienti, Jean-Jacques, Sormani, Maria Pia, Defer, Gilles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794160/
https://www.ncbi.nlm.nih.gov/pubmed/26983008
http://dx.doi.org/10.1371/journal.pone.0149685
_version_ 1782421443524427776
author Branger, Pierre
Parienti, Jean-Jacques
Sormani, Maria Pia
Defer, Gilles
author_facet Branger, Pierre
Parienti, Jean-Jacques
Sormani, Maria Pia
Defer, Gilles
author_sort Branger, Pierre
collection PubMed
description BACKGROUND: The quantification of brain atrophy in relapsing-remitting multiple sclerosis (RRMS) may serve as a marker of disease progression and treatment response. We compared the association between first-line (FL) or second-line (SL) disease-modifying drugs (DMDs) and brain volume changes over time in RRMS. MATERIALS AND METHODS: We reviewed clinical trials in RRMS between January 1, 1995 and June 1, 2014 that assessed the effect of DMDs and reported data on brain atrophy in Medline, Embase, the Cochrane database and meeting abstracts. First, we designed a meta-analysis to directly compare the percentage brain volume change (PBVC) between FLDMDs and SLDMDs at 24 months. Second, we conducted an observational and longitudinal linear regression analysis of a 48-month follow-up period. Sensitivity analyses considering PBVC between 12 and 48 months were also performed. RESULTS: Among the 272 studies identified, 117 were analyzed and 35 (18,140 patients) were included in the analysis. Based on the meta-analysis, atrophy was greater for the use of an FLDMD than that of an SLDMD at 24 months (primary endpoint mean difference, -0.86; 95% confidence interval: -1.57–-0.15; P = 0.02). Based on the linear regression analysis, the annual PBVC significantly differed between SLDMDs and placebo (-0.27%/y and -0.50%/y, respectively, P = 0.046) but not between FLDMDs (-0.33%/y) and placebo (P = 0.11) or between FLDMDs and SLDMDs (P = 0.49). Based on sensitivity analysis, the annual PBVC was reduced for SLDMDs compared with placebo (-0.14%/y and -0.56%/y, respectively, P<0.001) and FLDMDs (-0.46%/y, P<0.005), but no difference was detected between FLDMDs and placebo (P = 0.12). CONCLUSIONS: SLDMDs were associated with reduced PBVC slope over time in RRMS, regardless of the period considered. These results provide new insights into the mechanisms underlying atrophy progression in RRMS.
format Online
Article
Text
id pubmed-4794160
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-47941602016-03-23 The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis Branger, Pierre Parienti, Jean-Jacques Sormani, Maria Pia Defer, Gilles PLoS One Research Article BACKGROUND: The quantification of brain atrophy in relapsing-remitting multiple sclerosis (RRMS) may serve as a marker of disease progression and treatment response. We compared the association between first-line (FL) or second-line (SL) disease-modifying drugs (DMDs) and brain volume changes over time in RRMS. MATERIALS AND METHODS: We reviewed clinical trials in RRMS between January 1, 1995 and June 1, 2014 that assessed the effect of DMDs and reported data on brain atrophy in Medline, Embase, the Cochrane database and meeting abstracts. First, we designed a meta-analysis to directly compare the percentage brain volume change (PBVC) between FLDMDs and SLDMDs at 24 months. Second, we conducted an observational and longitudinal linear regression analysis of a 48-month follow-up period. Sensitivity analyses considering PBVC between 12 and 48 months were also performed. RESULTS: Among the 272 studies identified, 117 were analyzed and 35 (18,140 patients) were included in the analysis. Based on the meta-analysis, atrophy was greater for the use of an FLDMD than that of an SLDMD at 24 months (primary endpoint mean difference, -0.86; 95% confidence interval: -1.57–-0.15; P = 0.02). Based on the linear regression analysis, the annual PBVC significantly differed between SLDMDs and placebo (-0.27%/y and -0.50%/y, respectively, P = 0.046) but not between FLDMDs (-0.33%/y) and placebo (P = 0.11) or between FLDMDs and SLDMDs (P = 0.49). Based on sensitivity analysis, the annual PBVC was reduced for SLDMDs compared with placebo (-0.14%/y and -0.56%/y, respectively, P<0.001) and FLDMDs (-0.46%/y, P<0.005), but no difference was detected between FLDMDs and placebo (P = 0.12). CONCLUSIONS: SLDMDs were associated with reduced PBVC slope over time in RRMS, regardless of the period considered. These results provide new insights into the mechanisms underlying atrophy progression in RRMS. Public Library of Science 2016-03-16 /pmc/articles/PMC4794160/ /pubmed/26983008 http://dx.doi.org/10.1371/journal.pone.0149685 Text en © 2016 Branger et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Branger, Pierre
Parienti, Jean-Jacques
Sormani, Maria Pia
Defer, Gilles
The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis
title The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis
title_full The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis
title_fullStr The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis
title_full_unstemmed The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis
title_short The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis
title_sort effect of disease-modifying drugs on brain atrophy in relapsing-remitting multiple sclerosis: a meta-analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4794160/
https://www.ncbi.nlm.nih.gov/pubmed/26983008
http://dx.doi.org/10.1371/journal.pone.0149685
work_keys_str_mv AT brangerpierre theeffectofdiseasemodifyingdrugsonbrainatrophyinrelapsingremittingmultiplesclerosisametaanalysis
AT parientijeanjacques theeffectofdiseasemodifyingdrugsonbrainatrophyinrelapsingremittingmultiplesclerosisametaanalysis
AT sormanimariapia theeffectofdiseasemodifyingdrugsonbrainatrophyinrelapsingremittingmultiplesclerosisametaanalysis
AT defergilles theeffectofdiseasemodifyingdrugsonbrainatrophyinrelapsingremittingmultiplesclerosisametaanalysis
AT brangerpierre effectofdiseasemodifyingdrugsonbrainatrophyinrelapsingremittingmultiplesclerosisametaanalysis
AT parientijeanjacques effectofdiseasemodifyingdrugsonbrainatrophyinrelapsingremittingmultiplesclerosisametaanalysis
AT sormanimariapia effectofdiseasemodifyingdrugsonbrainatrophyinrelapsingremittingmultiplesclerosisametaanalysis
AT defergilles effectofdiseasemodifyingdrugsonbrainatrophyinrelapsingremittingmultiplesclerosisametaanalysis