A Cochrane review included 4 trials with 1477 patients with motoneuron disease. The trials examined tracheostomy-free survival. One trial (n=169) included older patients in more advanced stages of ALS. Riluzole 100 mg daily provided a benefit for the homogeneous group of patients in the first two trials (HR 0.80, 95% CI 0.64 to 0.99; 2 trials, n=323). When the third trial (including older and more seriously affected patients) was added, the overall treatment effect was reduced but still significant (HR 0.84, 95% CI 0.698 to 0.997; 3 trials, n=1282). This represented a 9% gain in the probability of surviving one year (49% in the placebo vs. 58% in the riluzole group), and increased median survival from 11.8 to 14.8 months. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. A three-fold increase in serum alanine transferase was more frequent in riluzole-treated patients than controls in the combined data (MD 2.62, 95% CI 1.59 to 4.31).
A systematic review including 2 trials with a total of 2,073 subjects was abstracted in DARE. Riluzole extended the time to tracheostomy or death, and the effect was greatest with dosage of 100 mg/d or greater. No effect on patient´s symptoms or global assessment was detected at 18 or 21 months. Transient elevations of hepatic transaminases were common. Also worsening of asthenia, nausea, vomiting, diarrhoea, anorexia, dizziness, vertigo, somnolence and mouth paresthesia were reported. Individual studies included in the meta-analysis Riluzole increases survival in ALS but does not improve functional ability. Two RCTs provide information on the efficacy of riluzole in the treatment of ALS. In the first study riluzole 100 mg/d was compared to placebo by using an intention-to-treat (ITR) analysis (155 patients). Riluzole decreased mortality by 38.6% at 12 months and 19.4% at 21 months.To confirm the therapeutic effect, a double-blind, placebo-controlled, multicenter, international, dose-ranging (50, 100, 200 mg/day), stratified study in 959 patients treated for up to 18 months was performed . The primary efficacy criterion was survival. Survival rates were: 50.4% (placebo), 56.8% (100 mg riluzole) (p = 0.05, Wilcoxon test; p = 0.076, log-rank test). At the end of the study, there was a significant dose-related decrease in risk of death or tracheostomy (p = 0.04). Adjustment for baseline prognostic factors showed a 35% decreased risk of death with the 100 mg/d dose compared with placebo (p = 0.002). No significant treatment effects were detected for the functional assessments. Survival curves (Kaplan-Meier) demonstrated a greater probability for survival beginning in the first 6 months of treatment and continuing throughout 15 months. The NNT was 6–9.
Riluzole 100 mg/d is not a cure for ALS, but offers a modest prolongation of survival when started early in the course of the disease. No exact data exist to predict how any individual patient will benefit from riluzole treatment.
Comment: The quality of evidence is downgraded by inconsistency (heterogeneity in patients and results).