This Article Full Text (PDF) All Versions of this Article: 1352458509102626v1 15/6/715    most recent References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Bosma, L. Articles by Uitdehaag, B. Search for Related Content PubMed PubMed Citation Articles by Bosma, L. Articles by Uitdehaag, B. Social Bookmarking                         What's this?

The search for responsive clinical endpoints in primary progressive multiple sclerosis

Department of Neurology, VU University Medical Center, Amsterdam, The Netherlandsl.bosma{at}vumc.nl

JJ Kragt

Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands

L Brieva

Unitat de Neuroimmunologia Clínica, Hospital Universitari Vall d’Hebron, Barcelona, Spain

Z Khaleeli

Department of Brain Repair and Rehabilitation, Institute of Neurology, University College, London, UK

X Montalban

Unitat de Neuroimmunologia Clínica, Hospital Universitari Vall d’Hebron, Barcelona, Spain

CH Polman

Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands

AJ Thompson

Department of Brain Repair and Rehabilitation, Institute of Neurology, University College, London, UK

M Tintoré

Unitat de Neuroimmunologia Clínica, Hospital Universitari Vall d’Hebron, Barcelona, Spain

BMJ Uitdehaag

Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands; Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands

Objective

To determine whether in primary progressive multiple sclerosis (PPMS) combining scores of Expanded Disability Status Scale (EDSS) with data from Timed 25-Foot Walk (T25FW) and 9-Hole Peg Test (9HPT) would produce a clinical endpoint that has a higher event rate than EDSS alone.

Methods

In a group of 161 PPMS patients, EDSS, T25FW, and 9HPT were performed at three time points over 2 years. We calculated how many patients showed clinically meaningful deterioration (or improvement) on individual and combined scales. We defined improvements on one scale with deterioration on the other as "opposing changes." We investigated the possible effect of baseline disability on the definition of our endpoint by dividing the population into two subsets of patients determined by baseline EDSS level.

Results

On individual scales, event rates were highest on T25FW: 34% and 46% 1 year and 2 years after baseline. On a combination of two scales, at 1 year the event rate was highest on T25FW/9HPT (46%; with a high rate of opposing changes) and at 2 years on T25FW/EDSS (57%; with a lower rate of opposing changes). In both subsets, event rates were highest on T25FW and (at 2 years) on the combination of T25FW/EDSS.

Conclusions

T25FW has the highest event rate as a single scale, independent of baseline disability level. A term of 2 years turned out to be more meaningful to observe than 1 year. "Worsening on either T25FW or EDSS" is the most appropriate composite endpoint in this patient group.

Key Words: 9HPT • clinical trials • EDSS • multiple sclerosis • outcome measurement • primary progressive • T25FW

This version was published on June 1, 2009

Multiple Sclerosis, Vol. 15, No. 6, 715-720 (2009)
DOI: 10.1177/1352458509102626


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?