Cargando…

Relating relapse and T2 lesion changes to disability progression in multiple sclerosis: a systematic literature review and regression analysis

BACKGROUND: In the treatment of multiple sclerosis (MS), the most important therapeutic aim of disease-modifying treatments (DMTs) is to prevent or postpone long-term disability. Given the typically slow progression observed in the majority of relapsing-remitting MS (RRMS) patients, the primary endp...

Descripción completa

Detalles Bibliográficos
Autores principales: Fahrbach, Kyle, Huelin, Rachel, Martin, Amber L, Kim, Edward, Dastani, Homa B, Rao, Stephen, Malhotra, Manoj
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225567/
https://www.ncbi.nlm.nih.gov/pubmed/24245966
http://dx.doi.org/10.1186/1471-2377-13-180
_version_ 1782343534229061632
author Fahrbach, Kyle
Huelin, Rachel
Martin, Amber L
Kim, Edward
Dastani, Homa B
Rao, Stephen
Malhotra, Manoj
author_facet Fahrbach, Kyle
Huelin, Rachel
Martin, Amber L
Kim, Edward
Dastani, Homa B
Rao, Stephen
Malhotra, Manoj
author_sort Fahrbach, Kyle
collection PubMed
description BACKGROUND: In the treatment of multiple sclerosis (MS), the most important therapeutic aim of disease-modifying treatments (DMTs) is to prevent or postpone long-term disability. Given the typically slow progression observed in the majority of relapsing-remitting MS (RRMS) patients, the primary endpoint for most randomized clinical trials (RCTs) is a reduction in relapse rate. It is widely assumed that reducing relapse rate will slow disability progression. Similarly, MRI studies suggest that reducing T2 lesions will be associated with slowing long-term disability in MS. The objective of this study was to evaluate the relationship between treatment effects on relapse rates and active T2 lesions to differences in disease progression (as measured by the Expanded Disability Status Scale [EDSS]) in trials evaluating patients with clinically isolated syndrome (CIS), RRMS, and secondary progressive MS (SPMS). METHODS: A systematic literature review was conducted in Medline, Embase, CENTRAL, and PsycINFO to identify randomized trials published in English from January 1, 1993-June 3, 2013 evaluating DMTs in adult MS patients using keywords for CIS, RRMS, and SPMS combined with keywords for relapse and recurrence. Eligible studies were required to report outcomes of relapse and T2 lesion changes or disease progression in CIS, RRMS, or SPMS patients receiving DMTs and have a follow-up duration of at least 22 months. Ultimately, 40 studies satisfied these criteria for inclusion. Regression analyses were conducted on RCTs to relate differences between the effect of treatments on relapse rates and on active T2 lesions to differences between the effects of treatments on disease progression (as measured by EDSS). RESULTS: Regression analysis determined there is a substantive clinically and statistically significant association between concurrent treatment effects in relapse rate and EDSS; p < 0.01. Lower treatment effects were associated with higher relative rates of disease progression. Significant associations between T2 lesion measures and EDSS measures also were found (p < 0.05), with some suggestion that the strength of the association may differ for older versus newer DMTs. CONCLUSIONS: Treatment differences in relapse reduction and T2 lesions are positively related to differences in disease progression over the first two years of treatment.
format Online
Article
Text
id pubmed-4225567
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-42255672014-11-12 Relating relapse and T2 lesion changes to disability progression in multiple sclerosis: a systematic literature review and regression analysis Fahrbach, Kyle Huelin, Rachel Martin, Amber L Kim, Edward Dastani, Homa B Rao, Stephen Malhotra, Manoj BMC Neurol Research Article BACKGROUND: In the treatment of multiple sclerosis (MS), the most important therapeutic aim of disease-modifying treatments (DMTs) is to prevent or postpone long-term disability. Given the typically slow progression observed in the majority of relapsing-remitting MS (RRMS) patients, the primary endpoint for most randomized clinical trials (RCTs) is a reduction in relapse rate. It is widely assumed that reducing relapse rate will slow disability progression. Similarly, MRI studies suggest that reducing T2 lesions will be associated with slowing long-term disability in MS. The objective of this study was to evaluate the relationship between treatment effects on relapse rates and active T2 lesions to differences in disease progression (as measured by the Expanded Disability Status Scale [EDSS]) in trials evaluating patients with clinically isolated syndrome (CIS), RRMS, and secondary progressive MS (SPMS). METHODS: A systematic literature review was conducted in Medline, Embase, CENTRAL, and PsycINFO to identify randomized trials published in English from January 1, 1993-June 3, 2013 evaluating DMTs in adult MS patients using keywords for CIS, RRMS, and SPMS combined with keywords for relapse and recurrence. Eligible studies were required to report outcomes of relapse and T2 lesion changes or disease progression in CIS, RRMS, or SPMS patients receiving DMTs and have a follow-up duration of at least 22 months. Ultimately, 40 studies satisfied these criteria for inclusion. Regression analyses were conducted on RCTs to relate differences between the effect of treatments on relapse rates and on active T2 lesions to differences between the effects of treatments on disease progression (as measured by EDSS). RESULTS: Regression analysis determined there is a substantive clinically and statistically significant association between concurrent treatment effects in relapse rate and EDSS; p < 0.01. Lower treatment effects were associated with higher relative rates of disease progression. Significant associations between T2 lesion measures and EDSS measures also were found (p < 0.05), with some suggestion that the strength of the association may differ for older versus newer DMTs. CONCLUSIONS: Treatment differences in relapse reduction and T2 lesions are positively related to differences in disease progression over the first two years of treatment. BioMed Central 2013-11-19 /pmc/articles/PMC4225567/ /pubmed/24245966 http://dx.doi.org/10.1186/1471-2377-13-180 Text en Copyright © 2013 Fahrbach et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Fahrbach, Kyle
Huelin, Rachel
Martin, Amber L
Kim, Edward
Dastani, Homa B
Rao, Stephen
Malhotra, Manoj
Relating relapse and T2 lesion changes to disability progression in multiple sclerosis: a systematic literature review and regression analysis
title Relating relapse and T2 lesion changes to disability progression in multiple sclerosis: a systematic literature review and regression analysis
title_full Relating relapse and T2 lesion changes to disability progression in multiple sclerosis: a systematic literature review and regression analysis
title_fullStr Relating relapse and T2 lesion changes to disability progression in multiple sclerosis: a systematic literature review and regression analysis
title_full_unstemmed Relating relapse and T2 lesion changes to disability progression in multiple sclerosis: a systematic literature review and regression analysis
title_short Relating relapse and T2 lesion changes to disability progression in multiple sclerosis: a systematic literature review and regression analysis
title_sort relating relapse and t2 lesion changes to disability progression in multiple sclerosis: a systematic literature review and regression analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225567/
https://www.ncbi.nlm.nih.gov/pubmed/24245966
http://dx.doi.org/10.1186/1471-2377-13-180
work_keys_str_mv AT fahrbachkyle relatingrelapseandt2lesionchangestodisabilityprogressioninmultiplesclerosisasystematicliteraturereviewandregressionanalysis
AT huelinrachel relatingrelapseandt2lesionchangestodisabilityprogressioninmultiplesclerosisasystematicliteraturereviewandregressionanalysis
AT martinamberl relatingrelapseandt2lesionchangestodisabilityprogressioninmultiplesclerosisasystematicliteraturereviewandregressionanalysis
AT kimedward relatingrelapseandt2lesionchangestodisabilityprogressioninmultiplesclerosisasystematicliteraturereviewandregressionanalysis
AT dastanihomab relatingrelapseandt2lesionchangestodisabilityprogressioninmultiplesclerosisasystematicliteraturereviewandregressionanalysis
AT raostephen relatingrelapseandt2lesionchangestodisabilityprogressioninmultiplesclerosisasystematicliteraturereviewandregressionanalysis
AT malhotramanoj relatingrelapseandt2lesionchangestodisabilityprogressioninmultiplesclerosisasystematicliteraturereviewandregressionanalysis