Objectives: We conducted a 6-month randomized, double-blind, placebo-controlled study to assess safety, tolerability, and efficacy of deferiprone in Friedreich’s ataxia.
Methods: Seventy-two patients were treated with deferiprone 20, 40, or 60 mg/kg/day or placebo, divided into two daily doses. Safety was the primary objective, secondary objectives included standardized neurological assessments (FARS, ICARS, 9HPT, T25FW, LCLA), general functional status (ADL), and cardiac assessments.
Results: Deferiprone was well tolerated at 20 mg/kg/day, whereas more adverse events occurred in the 40 mg/kg/day than in the placebo group. The 60mg/kg/day dose was discontinued due to worsening of ataxia in two patients. One patient on deferiprone 20 mg/kg/day experienced reversible neutropenia, but none developed agranulocytosis. Deferiprone-treated patients receiving 20 or 40 mg/kg/day showed a decline in the LV mass index, compared to an increase in the placebo-treated patients. Patients receiving 20 mg/kg/day of deferiprone had no significant change in FARS, similar to the placebo-treated patients, while those receiving 40 mg/kg/day had worsening in FARS and ICARS scores. The lack of deterioration in the placebo arm impaired the ability to detect any potential protective effect of deferiprone. However, subgroup analyses in patients with less severe disease suggested a benefit of deferiprone 20 mg/kg/day on ICARS, FARS, kinetic function and 9HPT.
Interpretation: This study demonstrated an acceptable safety profile of deferiprone at 20 mg/kg/day for the treatment of patients with FRDA. Subgroup analyses raise the possibility that, in patients with less severe disease, deferiprone 20 mg/kg/day may reduce disease progression, while higher doses appear to worsen ataxia. ANN NEUROL 2014. © 2014 American Neurological Association