Over a 12-month stretch, patients with spinocerebellar ataxia type 2 treated with riluzole showed significant worsening in Composite Cerebellar Functional Severity Score.
A recently conducted multicenter, double-blind, placebo-controlled trial found no evidence that riluzole (Rilutek; Sanofi), an FDA-approved drug for patients with amyotrophic lateral sclerosis, can improve clinical or radiological outcomes in patients with spinocerebellar ataxia type 2 (SCA2).
The data was presented at the International Parkinson and Movement Disorders Society (MDS) Virtual Congress 2021, September 17-22, by Giulia Coarelli, MD, department of neurology, Pitie-Salpetriere Hospital. Investigators also concluded however, that quantitative measures were more sensitive to change than clinical outcomes and correlated with cerebellar atrophy.
Between January 2018 and June 2019, a total of 45 patients with SCA2 were randomized to treatment with 50-mg riluzole (n = 22) or placebo (n = 23) for a 12-month period. Coarelli and colleagues used proportion of patients with 1-point improvement on Scale for the Assessment and Rating of Ataxia (SARA) score as the primary end point. Secondary end points included change of Composite Cerebellar Functional Severity Score (CCFS), Inventory of Non-Ataxia Signs (INAS), 36-item short form health survey questionnaire (SF-36), cerebellar and brainstem volumes, and clinical and biological tolerance of riluzole.
One patient in the placebo group dropped out due to disease worsening. Between both groups, investigators found no significance difference in proportion of patients with 1-point SARA score improvement (31.8% vs 40.9%; P = .75), as well as the variation of SARA score at month 12 (median, 0.5 [interquartile range (IQR), –1.5 to 2.0] vs 0.3 [IQR, –1.0 to 3.0]; P = .7). Among those who were treated with riluzole, CCFS scores worsened significantly over time (0.055 [IQR, 0.014-0.086] vs 0.004 [IQR, –0.040 to 0.020]; P <.01).
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Between treated and placebo patients, INAS variation was similar, without improvement in motor neuron signs (0 [IQR, –1 to 1] vs –1 [IQR, –2 to 0]; P = .07). Additionally, investigators observed a correlation at baseline between CCFS worsening and grey matter atrophy in the vermis (P = .04).
At month 12, volume loss was significant for brainstem volume changes such as left lobule Crus I (P = .001) and pons (P <.001) in the placebo group, but not significantly different in the treated group. There were no significant differences between the groups on SF-36 questionnaire. Notably, there were no increase in adverse events within the riluzole-treated group.
These results contrasted previously conducted research, which found some benefit for riluzole in this patient population. A study that included 40 patients presenting with cerebellar ataxias of different etiologies randomized to 100-mg riluzole showed that the drug reduces, by at least 5 points, the International Cooperative Ataxia Rating Scale (ICARS) score (risk difference, 63.2% [95% CI, 33.5%-79.9%]).2 Coarelli was a part of another study that showed decreased SARA scores in 50% (14 of 28) of patients with spinocerebellar ataxia or Friedrich ataxia treated with riluzole vs 11% (3 of 27) treated with placebo (OR, 8.00 [95% CI, 1.95-32.83]; P = .0020).3
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