A Rasch Analysis of the Charcot-Marie-Tooth Neuropathy Score (CMTNS) in a Cohort of Charcot-Marie-Tooth Type 1A Patients.

Wenjia Wang,Laurent Magy,Olivier Blin,Elisabeth Jouve,Niall P Murphy,Mickaël Guedj,Daniel Cohen,Julie Foucquier,Daniel Commenges,Cécile Proust-Lima,Shahram Attarian,Viviane Bertrand,Jong-Ling Fuh

doi:10.1371/journal.pone.0169878

Abstract

The Charcot-Marie-Tooth Neuropathy Score (CMTNS) was developed as a main efficacy endpoint for application in clinical trials of Charcot-Marie-Tooth disease type 1A (CMT1A). However, the sensitivity of the CMTNS for measuring disease severity and progression in CMT1A patients has been questioned. Here, we applied a Rasch analysis in a French cohort of patients to evaluate the psychometrical properties of the CMTNS. Overall, our analysis supports the validity of the CMTNS for application to CMT1A patients though with some limitations such as certain items of the CMTNS being more suitable for moderate to severe forms of the disease, and some items being disordered. We suggest that additional items and/or categories be considered to better assess mild-to-moderate patients.

Highlights

Charcot-Marie-Tooth (CMT) disease is the most common inherited disorder of the peripheral nervous system [1,2]
CMT type 1A (CMT1A) patients involved in this study initially participated in the French phase 2 clinical trial of ascorbic acid led by Micallef et al [9] and/or in the phase 2 clinical trial of PXT3003 led by Attarian et al [14] and/or in a subsequent non-investigational clinical study (BMK-CMT)
We performed a Rasch analysis of the Charcot-Marie-Tooth Neuropathy Score (CMTNS) using responses from the 277 individuals included in the study

Summary

Introduction

Charcot-Marie-Tooth (CMT) disease is the most common inherited disorder of the peripheral nervous system [1,2]. There are no approved treatments for CMT1A disease though there have been considerable interest in the potential of ascorbic acid (AA) as a therapy leading to six clinical trials investigating the efficacy of AA on CMT1A [6,7,8,9,10,11]. No beneficial clinical effects of AA were identified in any of these trials, as confirmed by two meta-analyses [12,13]. A clinical trial of PXT3003 (a fixed combination of baclofen, naltrexone and sorbitol) showed preliminary evidence of efficacy in an exploratory phase 2 study [14], which was confirmed by a meta-analysis [12]. A conclusion shared by all of these studies is that selecting a clinically meaningful efficacy endpoint for CMT1A trials is challenging. PLOS ONE | DOI:10.1371/journal.pone.0169878 January 17, 2017

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