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. 2024 Mar;39(3):510-518.
doi: 10.1002/mds.29687. Epub 2023 Dec 23.

Predictors of Survival in Friedreich's Ataxia: A Prospective Cohort Study

Elisabetta Indelicato  1 , Kathrin Reetz  2   3 , Sarah Maier  4 , Wolfgang Nachbauer  1 , Matthias Amprosi  1 , Paola Giunti  5 , Caterina Mariotti  6 , Alexandra Durr  7   8 , Francisco J R de Rivera Garrido  9 , Thomas Klopstock  10   11 , Ludger Schöls  12   13 , Thomas Klockgether  14   15 , Katrin Bürk  16 , Massimo Pandolfo  17   18 , Claire Didszun  2   3 , Marcus Grobe-Einsler  14   15 , Lorenzo Nanetti  6 , Lukas Nenning  1 , Stefan Kiechl  1   19 , Wolfgang Dichtl  20 , Hanno Ulmer  4 , Jörg B Schulz  2   3 , Sylvia Boesch  1 ; European Friedreich's Ataxia Consortium for Translational Studies (EFACTS)
Affiliations

Predictors of Survival in Friedreich's Ataxia: A Prospective Cohort Study

Elisabetta Indelicato et al. Mov Disord. 2024 Mar.

Abstract

Background: Friedreich's ataxia (FA) is a rare multisystemic disorder which can cause premature death.

Objectives: To investigate predictors of survival in FA.

Methods: Within a prospective registry established by the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS; ClinicalTrials.gov identifier NCT02069509) we enrolled genetically confirmed FA patients at 11 tertiary centers and followed them in yearly intervals. We investigated overall survival applying the Kaplan-Meier method, life tables, and log-rank test. We explored prognostic factors applying Cox proportional hazards regression and subsequently built a risk score which was assessed for discrimination and calibration performance.

Results: Between September 2010 and March 2017, we enrolled 631 FA patients. Median age at inclusion was 31 (range, 6-76) years. Until December 2022, 44 patients died and 119 terminated the study for other reasons. The 10-year cumulative survival rate was 87%. In a multivariable analysis, the disability stage (hazard ratio [HR] 1.51, 95% CI 1.08-2.12, P = 0.02), history of arrhythmic disorder (HR 2.93, 95% CI 1.34-6.39, P = 0.007), and diabetes mellitus (HR 2.31, 95% CI 1.05-5.10, P = 0.04) were independent predictors of survival. GAA repeat lengths did not improve the survival model. A risk score built on the previously described factors plus the presence of left ventricular systolic dysfunction at echocardiography enabled identification of four trajectories to prognosticate up to 10-year survival (log-rank test P < 0.001).

Conclusions: Arrhythmias, progressive neurological disability, and diabetes mellitus influence the overall survival in FA. We built a survival prognostic score which identifies patients meriting closer surveillance and who may benefit from early invasive cardiac monitoring and therapy. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: Friedreich's ataxia; cardiomyopathy; diabetes mellitus; disability stage; survival.

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