Late-Stage ALS Survival Prolonged with Riluzole

New findings suggest that riluzole prolongs survival in the final clinical stage of amyotrophic lateral sclerosis (ALS).

New findings suggest that riluzole prolongs survival in the final clinical stage of amyotrophic lateral sclerosis (ALS). It was previously understood that riluzole prolonged survival, but now researchers from the United Kingdom have pinpointed which stage this lengthening occurs.

The range of survival length with ALS is wide; in fact, according to the researchers, it can be as long as 20 years. Typically, medial survival from symptom onset is about 27.5 months for ith spinal bulbar onset or 35.9 months for those with spinal onset. By clarifying the disease into stages, studying the disease can be more functional, according to the study authors. They used King’s clinical staging system in this analysis, which was derived from standard clinical observations.

Previous literature determined that 100 mg riluzole was linked with a 35% reduction in mortality in a clinical trial. However, the investigators wanted to track which stage of ALS this effect took place: early stage of the disease, late stage, or spread throughout the course of the disease. To do so, the researchers retrospectively studied the 959 original trial patients who had probable or definite ALS defined by the El Escorial criteria within a time period ranging from December 1992 to November 1993. The patients were spread throughout Europe and North America.

Stage 4 of ALS is the stage at which respiratory or nutritional intervention is determined to be clinically necessary, study author Ton Fang, iBSc (Hons) explained to Rare Disease Report®. On King’s scale of clinical stages, 1 is early disease, 4 is late disease, and 5 is death.

There were 237 patients in the trial who were assigned to 50 mg daily riluzole, 236 patients on 100 mg riluzole daily, 244 patients receiving 200 mg rilozole daily, and 242 patients who received a placebo daily. While clinical stage at enrollment did not differ between the groups, the study authors learned that time in stage 4 was longer for patients who received 100 mg daily riluzole compared to those who had received the placebo. They also noted that time from stages 2 or 3 and the next stage (or death) was not different between the riluzole treatment groups and the placebo group.

Due to the trial’s design, Dr. Fang said, there was no information available on the participants at stage 1.

“Firstly, [these findings are important for] ensuring that patients and their relatives have the best possible information when making crucial medical decisions, where our research can better inform them of the clinical effects of riluzole,” he said.

The researchers stress the importance of understanding what exactly is being prolonged with the use of riluzole when it comes to ALS. Some patients or their relatives and caretakers may interpret the benefit of prolonging the later stage of the disease differently than benefitting from prolonging an earlier stage or prolonging the disease course in general; this is not what the study is implying.

Prolonging survival in stage 4 compared with earlier stages also has an economic impact, because later stages of ALS are linked with higher costs than the earlier stages. Thus, the study authors wrote, prolonging stage 4 is more expensive than prolonging stages 1 or 2.

“Additionally, our finding that riluzole works at the end stage of ALS leads to a greater understanding of both drug and disease mechanisms, both of which is currently unclear,” Dr. Fang said. “Our research also improves the awareness for using staging to determine the effects of treatment in neurodegenerative diseases, where TNM staging is already widely used in cancer research.”

Once it can be understood if riluzole can play a role in prolonging stage 1, clinical trials of treatments in ALS patients and other neurodegenerative diseases can move forward, the study authors concluded.