New drug for advanced stage of multiple sclerosis

Friday March 23 2018

"A new drug for multiple sclerosis could slow the progression of symptoms of a form of the disease for which effective treatments have proved elusive," The Guardian reports.

Multiple sclerosis (MS) is an autoimmune condition where the body's immune cells destroy the myelin coating protecting its nerve fibres. This leads to various nerve-related symptoms like problems with vision or balance.

Most people have symptoms that come and go with periods of recovery in between – this is called "relapsing remitting MS". But after many years most people eventually develop disabilities and problems that no longer fully go away, which is called "secondary progressive MS". There are fewer treatment options for this progressive stage.

The news headline refers to a large trial of 1,651 people with the progressive type of MS who were randomly given either placebo or a new drug called siponimod. Siponimod is thought to help reduce the damaging effects of harmful immune activity on nerves in the brain and spinal cord.

About a third of people taking the placebo had a significant worsening of MS symptoms (known as disease progression) over 3 months compared with only a quarter taking siponimod. Various side effects were more common with the drug, like low white blood cell count and slower heart rate.

There is a good possibility that this could soon become another treatment option for secondary progressive MS.

Where does the study come from?

The study was carried out by researchers from the University of Basel in Switzerland, University of Pennsylvania in the US, McGill University in Canada, the University of London, and various other institutions in North America and Europe.

Funding was provided by Novartis Pharma that manufactures the drug. The study was published in the peer-reviewed medical journal, The Lancet.

Almost all of the research team have worked, or currently work, for pharmaceutical companies.

The UK media's reporting of the study was accurate.

What kind of research was this?

This was a randomised controlled trial (RCT) to see whether the new drug siponimod could slow disease progression in people with secondary progressive MS.

Most of the disease-modifying drugs available for people with relapsing remitting MS aren't successful in slowing disease progression in people with secondary progressive MS. Siponimod mainly works by trapping the body's destructive white blood cells.

Early phase trials of this drug showed promising results. This trial called EXPAND (EXploring the efficacy and safety of siponimod in PAtients with secoNDary progressive multiple sclerosis), is one of the final stages of trials carried out in a large number of people with the condition. It was double-blinded so neither patients nor researchers knew if the person was taking the treatment or placebo. This gives a reliable indication of whether or not it works.

What did the researchers do?

The trial included 1,651 people with secondary progressive MS who were recruited from 292 hospitals in 31 countries.

Participants had moderate-to-advanced disability as confirmed by a score of between 3 and 6.5 on a 10-point disability scale (Expanded Disability Status Scale, EDSS), where a higher score indicates greater disability. They had a past history of relapsing remitting MS, and had documented disability progression in the past 2 years with no evidence of relapse in the past 3 months.

The siponimod tablets (2mg a day) were assigned to 1,105 people and the placebo tablet to 546.

Disability assessments were repeated every 3 months and the participants had annual MRI scans.

The main outcome of interest was disability progression over a 3-month period, confirmed by an increase in EDSS score of 1 point (if baseline score was 3-5) or 0.5 points (if baseline score was 5.5-6.5).

People who had continued disease progression over a 6-month period were given the choice of continuing in the trial not knowing what they were taking, switching to "open-label" treatment with siponimod, stopping all treatment, or trying another type of disease-modifying treatment for MS.

What were the basic results?

Average treatment period in the study was 18 months.

Siponimod reduced the risk of disease progression (worsening of symptoms) within any 3-month period. Only 26% of people taking siponimod had disease progression compared with 32% taking placebo (hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.65 to 0.95). Siponimod also reduced the likelihood of continued disease progression over 6 months.

People taking siponimod also had better walking scores and fewer signs of nerve damage on MRI scans. 82% of people completed treatment with siponimod compared with 78% taking placebo.

Side effects were slightly more common in the treatment group, affecting 89% taking siponimod and 82% taking placebo. Those that were more common with treatment included low white cell count and low heart rate – which are known side effects of this type of treatment.

What do the researchers conclude?

The researchers conclude that siponimod reduced the risk of disability progression with a safety profile similar to that of other drugs of this type. They say that this "is likely to be a useful treatment for [secondary progressive MS]".

Conclusions

This is a well-designed final stage trial with very promising results.

It includes a large number of people and larger studies usually provide a more reliable assessment of treatment effects.

The study was also double-blinded to ensure that neither patients nor assessors were aware of which treatment was being given. This should remove the possibility of bias from any disability assessments. To ensure blinding was maintained, all possible side effects were reported to independent assessors who weren't involved in the rest of the trial.

There are side effects from the treatment, which would need to be monitored, but it is difficult to avoid side effects with medications that are designed to suppress the immune system.

The study shows that this new drug is one step nearer to becoming a licensed treatment for people with secondary progressive MS. However, it's not yet possible to say for certain if or when it will become available outside of the research setting.

A new trial is being planned to assess the long-term effects of siponimod on people with secondary progressive MS.

Analysis by Bazian
Edited by NHS Choices