Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)
Abstract
Background
Riluzole has been approved for treatment of patients with amyotrophic lateral sclerosis in most countries. Questions persist about its clinical utility because of high cost and modest efficacy.
Objectives
To examine the efficacy of riluzole in prolonging survival, and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival.
Search methods
We updated the search of the Cochrane Neuromuscular Disease Group Trials Register for randomised trials in January 2008 and made enquiries of authors of trials, Aventis (manufacturer of riluzole) and other experts in the field. We searched MEDLINE (January 1966 to January 13 2008) and EMBASE (January 1980 to January 20 2008). No new randomised controlled trials were found.
Selection criteria
Types of studies: randomised trials
Types of participants: adults with a diagnosis of amyotrophic lateral sclerosis
Types of interventions: treatment with riluzole or placebo
Types of outcome measures:
Primary: pooled hazard ratio of tracheostomy‐free survival over all time points with riluzole 100 mg.
Secondary: per cent mortality with riluzole 50, 100 and 200 mg; neurologic function, muscle strength and adverse events.
Data collection and analysis
We identified four eligible randomised trials.
Main results
The four trials examining tracheostomy‐free survival included a total of 974 riluzole treated patients and 503 placebo treated patients. The methodological quality was acceptable and three trials were easily comparable, although one trial included older patients in more advanced stages of amyotrophic lateral sclerosis and one had multiple primary endpoints.
Riluzole 100 mg per day provided a benefit for the homogeneous group of patients in the first two trials (P value = 0.042, hazard ratio 0.80, 95% confidence interval 0.64 to 0.99) and there was no evidence of heterogeneity (P value = 0.33). When the third trial (which included older and more seriously affected patients) was added, there was evidence of heterogeneity (P value < 0.0001) and the random‐effects model, which takes this into account, resulted in the overall treatment effect estimate falling just short of significance (P value = 0.056, hazard ratio 0.84, 95% confidence interval 0.70 to 1.01). This represented a 9% gain in the probability of surviving one year (57% in the placebo and 66% in the riluzole group). There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. A threefold increase in serum alanine transferase was more frequent in riluzole treated patients than controls (weighted mean difference 2.62, 95% confidence interval 1.59 to 4.31).
Authors' conclusions
Riluzole 100 mg daily is reasonably safe and probably prolongs median survival by about two to three months in patients with amyotrophic lateral sclerosis.
PICOs
Plain language summary
Riluzole for amyotrophic lateral sclerosis (ALS)/ motor neuron disease (MND)
ALS/MND is a fatal neurological disease which produces paralysis of the limb, swallowing and breathing muscles. There is no available treatment to stop or reverse its progressive course.
In this review, the evidence from four randomized clinical trials involving 1477 patients with ALS is examined. The review was last updated in 2008. No new randomized controlled trials were found.The results indicate that riluzole 100 mg probably prolongs median survival in patients with amyotrophic lateral sclerosis by two to three months and the safety of the drug is not a major concern. The evidence from randomized controlled trials indicates that patients taking riluzole probably survive longer than patients taking placebo. The beneficial effects are very modest and the drug is expensive. Adverse effects from riluzole are relatively minor and for the most part reversible after stopping the drug.
