A recently published paper, reviewing 15 studies that investigated the effectiveness of riluzole as a treatment for MND in real-time, has suggested that the drug extends survival in people with the disease for much longer than was proposed in the original clinical trials.
Riluzole was approved by the US Food and Drug Administration (FDA) in 1995 following the completion of two randomised clinical trials (the ‘gold standard’ approach for evaluating how well drugs work against certain diseases) and is currently the only licensed drug available to people with MND in the UK that is known to extend survival time amongst patients. The clinical trials showed that although time to tracheostomy (where a tube is inserted into the windpipe, or trachea, to help with breathing) was significantly slowed, there was only a modest increase in average survival of between 2-3 months.
Clinical trials are traditionally designed with very strict inclusion/exclusion criteria and, therefore, do not include a wide cross-section of people living with the disease. They also have an end date, so the long-term effects of the drug are not observed. This means that, while the results can be considered scientifically trustworthy, they are limited in determining how the drug will perform in all patients with the disease. However, once a drug has been authorised, and is marketed as a treatment, it potentially becomes available to everyone and its effects on the general clinical population, over longer periods of time, can be studied. These are known as population studies.
In 2020, Andrews and colleagues identified 15 population studies that reported average survival time of people who were treated with riluzole compared to those who were not. Most of the studies found significant differences in survival between the two groups – between 6 and 19 months in people who had taken riluzole, which is substantially longer than survival times found in the original trials of the drug.
Why might we be seeing this difference in results?
The design of the original clinical trials of riluzole may offer up some explanation as to why the impact of survival was so different to that seen in real-world use.
It is possible that the trials underestimated the long-term benefit of riluzole due to short reporting time as survival was measured from time of enrolment to tracheostomy or death. Patients who were still alive and tracheostomy-free at the end of the trial were not included in analysis. Pre-clinical studies (which take place in animals before the drug is used in human trials), supported the long-term use of riluzole.
The authors also highlight research that suggests that riluzole may work in different ways in people in the early stages of MND compared to those in more advanced stages.
An extended length of time from diagnosis to initiation of riluzole in the clinical trials, ranging from 19-27 months, means that the trials were not designed to capture data regarding the effect of riluzole on survival in the early stages of the disease. Subsequent population studies have shown that the greatest benefit of riluzole occurs early in the disease, with little or no benefit if treatment is started more than 18-24 months after diagnosis.
This evidence points to the benefits for both early intervention and prolonged treatment with riluzole with the rationale that delaying motor neuron damage, and therefore delaying muscle degeneration, at earlier stages of the disease will prolong those stages associated with the best quality of life. Observations also support that survival benefits continue into later stages of the disease.
What does this mean for people living with MND?
Although population studies come with their own limitations, this review suggests that riluzole treatment may extend survival by 6-19 months, which is far longer than that reported in the original clinical trials and holds more promise for people living with the disease now.
Real-world evidence studies provide valuable information about how a drug performs in a broader patient population, and how this is observed by clinicians, outside clinical trials. This review has highlighted new data about specific benefits of riluzole therapy that were not represented in the original trial results. It will help to positively influence the conversation that clinicians have with their patients on the benefits of riluzole treatments, equipping them with better information on how to customise treatment.
- Read the full paper: Real-world evidence of riluzole effectiveness in treating amyotrophic lateral sclerosis – Jinsy A. Andrews, Carlayne E. Jackson, Terry D. Heiman-Patterson, Paolo Bettica, Benjamin Rix Brooks and Erik P. Pioro
- For more information about clinical trials, and how they work, see Information Sheet D: Clinical Trials
- For more information on treatments and medication for MND, please see our website.