Those findings were reported by a team led by King’s College London researchers and published in The Lancet Neurology. The study was titled “Stage at which riluzole treatment prolongs survival in patients with amyotrophic lateral sclerosis: a retrospective analysis of data from a dose-ranging study.”
Rilutek was the first ALS drug to be approved by the U.S. Food and Drug Administration. Although it is not fully understood how it works, several clinical studies have demonstrated its potential to extend patients’ survival.
However, these same studies have failed to clarify the affects of Rilutek at different stages of the disease and which patients may benefit the most from this treatment.
In the recent study, researchers reviewed the clinical records of 959 ALS patients who participated in the initial dose-ranging study of Rilutek. During this trial patients were selected randomly to receive 50 mg, 100 mg, or 200 mg per day of Rilutek, or daily placebo.
When the trial was conducted, between December 1992 and December 1994, disease staging scales were not yet clear. Patients were classified based on whether they had had a tracheostomy (a surgically made direct airway connection in the neck).
To better categorize patients, the team re-analyzed their clinical records and applied the King’s clinical staging system. This scoring system ranges from range from 1 (early disease) to 4 (late disease), with stage 5 being death. It takes into account different motor impairments that characterized ALS progression, as well as late stage nutritional and respiratory failure.
Based on the estimated staging, 355 patients were enrolled in the study at ALS stage 2, 451 at stage 3, and 153 at stage 4.
Analysis revealed that Rilutek treatment did not significantly change disease progression rates compared to placebo in patients at stages 2 and 3.
In contrast, patients at stage 4 treated with the drug experienced extended survival compared to those treated with placebo. The more significant effect was seen in the group treated with 100 mg per day of Rilutek, who experienced a reduction of 45 percent in the risk of stage transitioning, compared to placebo.
Next, the researchers performed a similar analysis, but with clinical data collected during the LiCALS trial (2008-006891-31). This study included 217 ALS patients who were assigned randomly to receive lithium or placebo. The analysis revealed that lithium treatment did not change the time patients remained in each disease stage compared to placebo. This demonstrated that the effect seen in the dose-ranging study was specific of Rilutek’s effect and not a statistical or analysis-driven consequence.
The researchers believe these results show that Rilutek “acts by prolonging stage 4 ALS rather than by slowing the entire disease course or prolonging intermediate stages.”
Such analysis approach “should be used in future clinical trials of ALS or other neurodegenerative diseases,” to better recognize treatment benefits and “to allow a full discussion of effects when counseling patients about treatment,” they added.