Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND).
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.


OBJECTIVE
To examine the efficacy of riluzole in prolonging survival, and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival.


METHODS
We searched the Cochrane Neuromuscular Disease Group Register for randomized trials in December 2004 and made enquiries of authors of trials, Aventis (manufacturer of riluzole) and other experts in the field. We searched MEDLINE (January 1966 to August 25 2006) and EMBASE (January 1980 to September 30th 2006).


METHODS
Types of studies: randomized trials.


METHODS
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.


METHODS
We identified four eligible randomized trials.


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).


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.
Miller
R G
RG
California Pacific Medical Center, Department of Neurosciences, 2324 Sacramento Street, Suite 150, San Francisco, California 94115, USA. millerrx@sutterhealth.org
Mitchell
J D
JD
Lyon
M
M
Moore
D H
DH
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008017:Life Expectancy; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D019782:Riluzole / Q000009:adverse effects / Q000627:therapeutic use*
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D019782:Riluzole