Researchers assessed the progression of symptoms among patients with Friedreich ataxia during a prospective, observational cohort study. Their results, published in Lancet Neurology, may help inform clinical trial designs and allow clinicians to better tailor therapies.

The European Friedreich Ataxia Consortium for Translational Studies (EFACTS) study recruited patients at 11 university hospitals, 5 in Germany and I hospital each in Austria, Belgium, France, Italy, Spain, and the United Kingdom between 2010 and 2018. Yearly, patients underwent genetic testing and Scale for the Assessment and Rating of Ataxia (SARA), activities of daily living (ADL) scale, Inventory of Non-Ataxia Signs (INAS), Spinocerebellar Ataxia Functional Index (SCAFI), and EQ-5D evaluations.

A total of 602 patients were recruited at baseline, and 500 had 1-year, 465 had 2-year, 374 had 3-year, and 366 had 4-year follow-up data. Most patients were homozygous for expanded GAA repeats in the frataxin (FXN) gene and had typical-onset disease (84%).


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At baseline, half of patients were ambulatory (51%), and 51 patients lost ambulation during follow-up.

The SARA standardized response mean increased from 0.32 points at 1-year to 0.90 points at year 4 and ADL from 0.35 to 1.05 points. These values corresponded with an annual worsening of 0.82 (standard error [SE], 0.05) points for SARA and 0.93 (SE, 0.05) points for ADL.

Stratified by ambulatory status, patients who were ambulatory had significantly greater SARA progression rates (1.12 vs 0.50 points; time by group interaction, 0.62 points; P <.0001). No significant difference for ADL was observed on the basis of ambulatory status.

SCAFI scores progressed at an annual rate of -0.05 (SE, 0.01) points. Progression of SCAFI was increased among ambulatory patients with a significant time by group interaction (-0.04; SE, 0.01 points; P =.012). EQ-5D scores progressed by -0.02 (SE, 0.003) points annually with a significant difference on the basis of onset (0.02; SE, 0.01 points; P =.030) and a time by group interaction in which non-ambulatory status progressed more rapidly (0.02; SE, 0.006 points; P <.0001). INAS scores increased by 0.09 (SE, 0.02) points every year.

A breakpoint analysis determined that patients who were younger than 27 years of age at baseline had increased annual SARA progression (1.31 vs 0.56 points) as did patients with at least 347 GAA repeats (1.25 vs 0.99 points). Annual ADL progression was associated with disease onset before 6 years of age (1.44 vs 0.88 points) and among patients who lost ambulation before 11 years of age (1.45 vs 0.89 points).

This study was limited by its relatively low retention rates through year 4.

These data have important implications to consider in the design of clinical trials for studying Friedreich ataxia. The study authors concluded that “ADL with its simple applicability and sensitivity to change is well suited to serve as a functional primary outcome for clinical trials in [Friedreich] ataxia.”

Disclosure: This research was supported by Voyager Therapeutics. Please see the original article for a full list of disclosures.

Reference

Reetz K, Dogan I, Hilgers RD, et al; EFACTS study group. Progression characteristics of the European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS): a 4-year cohort study. Lancet Neurol. 2021;20(5):362-372. doi:10.1016/S1474-4422(21)00027-2



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