Biological and clinical characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) cohort

A cross-sectional analysis of baseline data

Kathrin Reetz, Imis Dogan, Ana S. Costa, Manuel Dafotakis, Kathrin Fedosov, Paola Giunti, Michael H. Parkinson, Mary G. Sweeney, Caterina Mariotti, Marta Panzeri, Lorenzo Nanetti, Javier Arpa, Irene Sanz-Gallego, Alexandra Durr, Perrine Charles, Sylvia Boesch, Wolfgang Nachbauer, Thomas Klopstock, Ivan Karin, Chantal Depondt & 7 others Jennifer Müller vom Hagen, Ludger Schöls, Ilaria A. Giordano, Thomas Klockgether, Katrin Bürk, Massimo Pandolfo, Jörg B. Schulz

Research output: Contribution to journalArticle

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Abstract

Background: Friedreich's ataxia is a rare autosomal recessive neurodegenerative disorder. Here we report cross-sectional baseline data to establish the biological and clinical characteristics for a prospective, international, European Friedreich's ataxia database registry. Methods: Within the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) framework, we assessed a cohort of patients with genetically confirmed Friedreich's ataxia. The primary outcome measure was the Scale for the Assessment and Rating of Ataxia (SARA) and secondary outcome measures were the Inventory of Non-Ataxia Signs (INAS), the performance-based coordination test Spinocerebellar Ataxia Functional Index (SCAFI), the neurocognitive phonemic verbal fluency test, and two quality-of-life measures: the activities of daily living (ADL) part of the Friedreich's Ataxia Rating Scale and EQ-5D. The Friedreich's ataxia cohort was subdivided into three groups: early disease onset (≤14 years), intermediate onset (15-24 years), and late onset (≥25 years), which were compared for clinical characteristics and outcome measures. We used linear regression analysis to estimate the annual decline of clinical outcome measures based on disease duration. This study is registered with ClinicalTrials.gov, number NCT02069509. Findings: We enrolled 592 patients with genetically confirmed Friedreich's ataxia between Sept 15, 2010, and April 30, 2013, at 11 sites in seven European countries. Age of disease onset was inversely correlated with the number of GAA repeats in the frataxin (. FXN) gene: every 100 GAA repeats on the smaller repeat allele was associated with a 2·3 year (SE 0·2) earlier onset. Regression analyses showed significant estimated annual worsening of SARA (regression coefficient 0·86 points [SE 0·05], INAS (0·14 points [0·01]), SCAFI Z scores (-0·09 [0·01]), verbal fluency (-0·34 words [0·07]), and ADL (0·64 points [0·04]) during the first 25 years of disease; the regression slope for health-related quality-of-life state from EQ-5D was not significant (-0·33 points [0·18]). For SARA, the predicted annual rate of worsening was significantly higher in early-onset patients (n=354; 1·04 points [0·13]) and intermediate-onset patients (n=137; 1·17 points [0·22]) than in late-onset patients (n=100; 0·56 points [0·10]). Interpretation: The results of this cross-sectional baseline analysis of the EFACTS cohort suggest that earlier disease onset is associated with larger numbers of GAA repeats and more rapid disease progression. The differential estimated progression of ataxia symptoms related to age of onset have implications for the design of clinical trials in Friedreich's ataxia, for which SARA might be the most suitable measure to monitor disease progression. Funding: European Commission.

Original languageEnglish
Pages (from-to)174-182
Number of pages9
JournalThe Lancet Neurology
Volume14
Issue number2
DOIs
Publication statusPublished - 2015

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Friedreich Ataxia
Cohort Studies
Cross-Sectional Studies
Ataxia
Outcome Assessment (Health Care)
Spinocerebellar Ataxias
Activities of Daily Living
Age of Onset
Disease Progression
Regression Analysis
Quality of Life
Equipment and Supplies
Neurodegenerative Diseases
Registries
Linear Models
Alleles
Clinical Trials
Databases

ASJC Scopus subject areas

  • Clinical Neurology
  • Medicine(all)

Cite this

Biological and clinical characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) cohort : A cross-sectional analysis of baseline data. / Reetz, Kathrin; Dogan, Imis; Costa, Ana S.; Dafotakis, Manuel; Fedosov, Kathrin; Giunti, Paola; Parkinson, Michael H.; Sweeney, Mary G.; Mariotti, Caterina; Panzeri, Marta; Nanetti, Lorenzo; Arpa, Javier; Sanz-Gallego, Irene; Durr, Alexandra; Charles, Perrine; Boesch, Sylvia; Nachbauer, Wolfgang; Klopstock, Thomas; Karin, Ivan; Depondt, Chantal; vom Hagen, Jennifer Müller; Schöls, Ludger; Giordano, Ilaria A.; Klockgether, Thomas; Bürk, Katrin; Pandolfo, Massimo; Schulz, Jörg B.

In: The Lancet Neurology, Vol. 14, No. 2, 2015, p. 174-182.

Research output: Contribution to journalArticle

Reetz, K, Dogan, I, Costa, AS, Dafotakis, M, Fedosov, K, Giunti, P, Parkinson, MH, Sweeney, MG, Mariotti, C, Panzeri, M, Nanetti, L, Arpa, J, Sanz-Gallego, I, Durr, A, Charles, P, Boesch, S, Nachbauer, W, Klopstock, T, Karin, I, Depondt, C, vom Hagen, JM, Schöls, L, Giordano, IA, Klockgether, T, Bürk, K, Pandolfo, M & Schulz, JB 2015, 'Biological and clinical characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) cohort: A cross-sectional analysis of baseline data', The Lancet Neurology, vol. 14, no. 2, pp. 174-182. https://doi.org/10.1016/S1474-4422(14)70321-7
Reetz, Kathrin ; Dogan, Imis ; Costa, Ana S. ; Dafotakis, Manuel ; Fedosov, Kathrin ; Giunti, Paola ; Parkinson, Michael H. ; Sweeney, Mary G. ; Mariotti, Caterina ; Panzeri, Marta ; Nanetti, Lorenzo ; Arpa, Javier ; Sanz-Gallego, Irene ; Durr, Alexandra ; Charles, Perrine ; Boesch, Sylvia ; Nachbauer, Wolfgang ; Klopstock, Thomas ; Karin, Ivan ; Depondt, Chantal ; vom Hagen, Jennifer Müller ; Schöls, Ludger ; Giordano, Ilaria A. ; Klockgether, Thomas ; Bürk, Katrin ; Pandolfo, Massimo ; Schulz, Jörg B. / Biological and clinical characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) cohort : A cross-sectional analysis of baseline data. In: The Lancet Neurology. 2015 ; Vol. 14, No. 2. pp. 174-182.
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abstract = "Background: Friedreich's ataxia is a rare autosomal recessive neurodegenerative disorder. Here we report cross-sectional baseline data to establish the biological and clinical characteristics for a prospective, international, European Friedreich's ataxia database registry. Methods: Within the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) framework, we assessed a cohort of patients with genetically confirmed Friedreich's ataxia. The primary outcome measure was the Scale for the Assessment and Rating of Ataxia (SARA) and secondary outcome measures were the Inventory of Non-Ataxia Signs (INAS), the performance-based coordination test Spinocerebellar Ataxia Functional Index (SCAFI), the neurocognitive phonemic verbal fluency test, and two quality-of-life measures: the activities of daily living (ADL) part of the Friedreich's Ataxia Rating Scale and EQ-5D. The Friedreich's ataxia cohort was subdivided into three groups: early disease onset (≤14 years), intermediate onset (15-24 years), and late onset (≥25 years), which were compared for clinical characteristics and outcome measures. We used linear regression analysis to estimate the annual decline of clinical outcome measures based on disease duration. This study is registered with ClinicalTrials.gov, number NCT02069509. Findings: We enrolled 592 patients with genetically confirmed Friedreich's ataxia between Sept 15, 2010, and April 30, 2013, at 11 sites in seven European countries. Age of disease onset was inversely correlated with the number of GAA repeats in the frataxin (. FXN) gene: every 100 GAA repeats on the smaller repeat allele was associated with a 2·3 year (SE 0·2) earlier onset. Regression analyses showed significant estimated annual worsening of SARA (regression coefficient 0·86 points [SE 0·05], INAS (0·14 points [0·01]), SCAFI Z scores (-0·09 [0·01]), verbal fluency (-0·34 words [0·07]), and ADL (0·64 points [0·04]) during the first 25 years of disease; the regression slope for health-related quality-of-life state from EQ-5D was not significant (-0·33 points [0·18]). For SARA, the predicted annual rate of worsening was significantly higher in early-onset patients (n=354; 1·04 points [0·13]) and intermediate-onset patients (n=137; 1·17 points [0·22]) than in late-onset patients (n=100; 0·56 points [0·10]). Interpretation: The results of this cross-sectional baseline analysis of the EFACTS cohort suggest that earlier disease onset is associated with larger numbers of GAA repeats and more rapid disease progression. The differential estimated progression of ataxia symptoms related to age of onset have implications for the design of clinical trials in Friedreich's ataxia, for which SARA might be the most suitable measure to monitor disease progression. Funding: European Commission.",
author = "Kathrin Reetz and Imis Dogan and Costa, {Ana S.} and Manuel Dafotakis and Kathrin Fedosov and Paola Giunti and Parkinson, {Michael H.} and Sweeney, {Mary G.} and Caterina Mariotti and Marta Panzeri and Lorenzo Nanetti and Javier Arpa and Irene Sanz-Gallego and Alexandra Durr and Perrine Charles and Sylvia Boesch and Wolfgang Nachbauer and Thomas Klopstock and Ivan Karin and Chantal Depondt and {vom Hagen}, {Jennifer M{\"u}ller} and Ludger Sch{\"o}ls and Giordano, {Ilaria A.} and Thomas Klockgether and Katrin B{\"u}rk and Massimo Pandolfo and Schulz, {J{\"o}rg B.}",
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TY - JOUR

T1 - Biological and clinical characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) cohort

T2 - A cross-sectional analysis of baseline data

AU - Reetz, Kathrin

AU - Dogan, Imis

AU - Costa, Ana S.

AU - Dafotakis, Manuel

AU - Fedosov, Kathrin

AU - Giunti, Paola

AU - Parkinson, Michael H.

AU - Sweeney, Mary G.

AU - Mariotti, Caterina

AU - Panzeri, Marta

AU - Nanetti, Lorenzo

AU - Arpa, Javier

AU - Sanz-Gallego, Irene

AU - Durr, Alexandra

AU - Charles, Perrine

AU - Boesch, Sylvia

AU - Nachbauer, Wolfgang

AU - Klopstock, Thomas

AU - Karin, Ivan

AU - Depondt, Chantal

AU - vom Hagen, Jennifer Müller

AU - Schöls, Ludger

AU - Giordano, Ilaria A.

AU - Klockgether, Thomas

AU - Bürk, Katrin

AU - Pandolfo, Massimo

AU - Schulz, Jörg B.

PY - 2015

Y1 - 2015

N2 - Background: Friedreich's ataxia is a rare autosomal recessive neurodegenerative disorder. Here we report cross-sectional baseline data to establish the biological and clinical characteristics for a prospective, international, European Friedreich's ataxia database registry. Methods: Within the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) framework, we assessed a cohort of patients with genetically confirmed Friedreich's ataxia. The primary outcome measure was the Scale for the Assessment and Rating of Ataxia (SARA) and secondary outcome measures were the Inventory of Non-Ataxia Signs (INAS), the performance-based coordination test Spinocerebellar Ataxia Functional Index (SCAFI), the neurocognitive phonemic verbal fluency test, and two quality-of-life measures: the activities of daily living (ADL) part of the Friedreich's Ataxia Rating Scale and EQ-5D. The Friedreich's ataxia cohort was subdivided into three groups: early disease onset (≤14 years), intermediate onset (15-24 years), and late onset (≥25 years), which were compared for clinical characteristics and outcome measures. We used linear regression analysis to estimate the annual decline of clinical outcome measures based on disease duration. This study is registered with ClinicalTrials.gov, number NCT02069509. Findings: We enrolled 592 patients with genetically confirmed Friedreich's ataxia between Sept 15, 2010, and April 30, 2013, at 11 sites in seven European countries. Age of disease onset was inversely correlated with the number of GAA repeats in the frataxin (. FXN) gene: every 100 GAA repeats on the smaller repeat allele was associated with a 2·3 year (SE 0·2) earlier onset. Regression analyses showed significant estimated annual worsening of SARA (regression coefficient 0·86 points [SE 0·05], INAS (0·14 points [0·01]), SCAFI Z scores (-0·09 [0·01]), verbal fluency (-0·34 words [0·07]), and ADL (0·64 points [0·04]) during the first 25 years of disease; the regression slope for health-related quality-of-life state from EQ-5D was not significant (-0·33 points [0·18]). For SARA, the predicted annual rate of worsening was significantly higher in early-onset patients (n=354; 1·04 points [0·13]) and intermediate-onset patients (n=137; 1·17 points [0·22]) than in late-onset patients (n=100; 0·56 points [0·10]). Interpretation: The results of this cross-sectional baseline analysis of the EFACTS cohort suggest that earlier disease onset is associated with larger numbers of GAA repeats and more rapid disease progression. The differential estimated progression of ataxia symptoms related to age of onset have implications for the design of clinical trials in Friedreich's ataxia, for which SARA might be the most suitable measure to monitor disease progression. Funding: European Commission.

AB - Background: Friedreich's ataxia is a rare autosomal recessive neurodegenerative disorder. Here we report cross-sectional baseline data to establish the biological and clinical characteristics for a prospective, international, European Friedreich's ataxia database registry. Methods: Within the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) framework, we assessed a cohort of patients with genetically confirmed Friedreich's ataxia. The primary outcome measure was the Scale for the Assessment and Rating of Ataxia (SARA) and secondary outcome measures were the Inventory of Non-Ataxia Signs (INAS), the performance-based coordination test Spinocerebellar Ataxia Functional Index (SCAFI), the neurocognitive phonemic verbal fluency test, and two quality-of-life measures: the activities of daily living (ADL) part of the Friedreich's Ataxia Rating Scale and EQ-5D. The Friedreich's ataxia cohort was subdivided into three groups: early disease onset (≤14 years), intermediate onset (15-24 years), and late onset (≥25 years), which were compared for clinical characteristics and outcome measures. We used linear regression analysis to estimate the annual decline of clinical outcome measures based on disease duration. This study is registered with ClinicalTrials.gov, number NCT02069509. Findings: We enrolled 592 patients with genetically confirmed Friedreich's ataxia between Sept 15, 2010, and April 30, 2013, at 11 sites in seven European countries. Age of disease onset was inversely correlated with the number of GAA repeats in the frataxin (. FXN) gene: every 100 GAA repeats on the smaller repeat allele was associated with a 2·3 year (SE 0·2) earlier onset. Regression analyses showed significant estimated annual worsening of SARA (regression coefficient 0·86 points [SE 0·05], INAS (0·14 points [0·01]), SCAFI Z scores (-0·09 [0·01]), verbal fluency (-0·34 words [0·07]), and ADL (0·64 points [0·04]) during the first 25 years of disease; the regression slope for health-related quality-of-life state from EQ-5D was not significant (-0·33 points [0·18]). For SARA, the predicted annual rate of worsening was significantly higher in early-onset patients (n=354; 1·04 points [0·13]) and intermediate-onset patients (n=137; 1·17 points [0·22]) than in late-onset patients (n=100; 0·56 points [0·10]). Interpretation: The results of this cross-sectional baseline analysis of the EFACTS cohort suggest that earlier disease onset is associated with larger numbers of GAA repeats and more rapid disease progression. The differential estimated progression of ataxia symptoms related to age of onset have implications for the design of clinical trials in Friedreich's ataxia, for which SARA might be the most suitable measure to monitor disease progression. Funding: European Commission.

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