Riluzole ineffective for treatment of moderate spinocerebellar ataxia type 2

Riluzole did not improve clinical or radiological outcomes in patients with moderate spinocerebellar ataxia type 2, according to study results published in Lancet Neurology.

“Several disease-modifying treatments have been tested in hereditary ataxias, such as valproic acid or lithium, without demonstrated efficacy to support their clinical use. However, the effect of riluzole has been reported as beneficial in two trials,” Giulia Coarelli, MD, of the department of neurology at Sorbonne University in Paris, and colleagues wrote.

Researchers sought to assess the safety and efficacy of riluzole in patients with spinocerebellar ataxia type 2 by conducting a randomized, double-blind, placebo-controlled multicenter trial. The glutamate-blocking drug is reportedly beneficial for patients with cerebellar ataxia, but true effectiveness within a disease subtype is unclear.

The study was conducted between Jan. 18, 2018, and June 14, 2019, and included 45 participants with spinocerebellar ataxia type 2, with age of onset up to 50 years. All patients had moderate-stage disease, as evidenced by a median scale for the assessment and rating of ataxia (SARA) score of 13.5.

On a 1:1 basis, patients were given either a 50-mg oral dose of riluzole or placebo twice a day for 12 months. Participants were evaluated at two visits, at baseline and trial end, during which clinical measures and a 3T brain MRI were performed.

The primary endpoint for the study was the proportion of participants whose SARA score improved by 1 point or more.

Results showed that after 12 months SARA score improvements were observed in seven patients (32%) in the riluzole group, compared with nine patients (39%) in the placebo group, with a mean difference of –10.3% (95% CI, –37.4% to 19.2%). SARA score worsened with a median increase of 0.5 points in the riluzole group vs. 0.3 points in the placebo group (P = 0.70).

Participants given riluzole displayed no serious adverse effects, while four patients in placebo group reported serious negative events, including hepatic enzyme increase, fracture of external malleolus, rectorrhagia and depression. Overall, the incidence of adverse events was roughly equal among riluzole (16) and placebo (19) patients.

In addition, MRI volumetry showed that cerebellar and brainstem volumes decreased over 12 months in both the riluzole and placebo groups.

“We found no improvement in clinical and radiological outcomes, despite satisfactory treatment compliance and an absence of serious adverse events,” Coarelli and colleagues wrote. “Although this result does not exclude a possible positive effect of riluzole on other forms of cerebellar ataxia, it illustrates the need to evaluate treatments in  homogeneous groups of patients, even in rare diseases.”