• Clinical trials have been conducted to see whether an existing asthma medication, ibudilast, can be repurposed as a treatment for progressive forms of MS
      • The medication is known to cross the blood-brain-barrier and has been shown in the laboratory to inhibit several molecules that promote inflammation in the central nervous system
      • This phase II clinical trial showed that ibudilast reduced the rate of brain tissue loss by 48% compared to a placebo in people with both primary and secondary progressive MS
      • This trial was the first step in testing the medication for progressive MS and was not designed to show changes to disability accumulation; this will need to be tested in further clinical trials

Results of a phase II clinical trial have shown that an experimental medication may halve the rate of brain tissue loss in progressive forms of MS. Loss of brain tissue has been associated with poor outcomes for people with MS, so this is an encouraging result that suggests further trials of the drug should be conducted to see if it can slow or prevent disability accumulation.

The drug, known as ibudilast, is a medication that is already in use in Asia to treat asthma, but it has since been identified in laboratory experiments as a potential drug that can cross into the brain and influence the activity of the immune system there.
The drug was previously tested in people with relapsing MS in a clinical trial that was published in 2010. In that initial trial ibudilast failed to prevent relapses or the development of new lesions seen in MRI scans, but it did slow the progression of brain atrophy (shrinkage). On this basis, the investigators decided to test the drug in progressive forms of MS to see if it could protect the central nervous system and prevent disease progression.


The new SPRINT-MS trial, led by Professor Robert Fox of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic in Ohio, USA, was conducted at 28 US sites. The results were published in the prestigious New England Journal of Medicine in September. The trial enrolled 255 people with secondary and primary progressive MS in approximately equal numbers. Half of each group was randomly assigned to receive either 100mg per day of ibudilast or a placebo treatment.

The participants were then tracked using a number of different MRI brain scan measures, the primary measure being the change in total brain volume over the 96 week study period. Brain scanning measurements known as diffusion tensor imaging and magnetisation transfer ratio were also performed to measure the integrity of brain tissue. Since the optic nerve is commonly damaged in people with MS, scans were also performed to measure the thickness of the retinal nerve fibre layer in the back of the eye. Disability progression, meanwhile, was measured using the EDSS score.

After 96 weeks on treatment, the researchers found the amount of brain shrinkage in people receiving ibudilast was half that of those on the placebo. This equated to approximately 2.5ml less brain tissue lost across the trial period for those on ibudilast.
The other outcome measures of brain tissue integrity, retinal nerve fibre layer thickness and EDSS scores also showed some differences, but the trial was not designed to provide a statistically significant assessment of these differences.

Adverse events

As with any medication being tested in a new situation, researchers also tracked any adverse events experienced by the participants. Adverse events are any health issues that may or may not be related to the medication. If the adverse events appear more commonly in the treatment group than the placebo group, this may indicate that these are side effects of the medication. The number of participants experiencing any type of adverse event was slightly higher in the ibudilast group (92%) compared to the placebo group (88%) and the types of adverse events that appeared to be more common in the ibudilast-treated group were predominantly gastrointestinal (nausea, diarrhoea, abdominal pain and vomiting), headache and depression. There was no difference noted in the number or type of infections experienced among the two groups.

While it is not possible to directly compare the results from different clinical trials due to different patient groups, different trial protocols and different atrophy measurements, the researchers noted that the significant effect of ibudilast on brain atrophy was at least comparable to other recent clinical trials of some other MS medications that slowed atrophy by 15% (siponimod), 17.5% (ocrelizumab) and 43% (simvastatin).

Whilst this phase II trial design has not been able to demonstrate a clear clinical impact of the treatment on disability, the slowing of brain tissue loss and the apparent safety of the treatment in people with progressive MS is very encouraging. Further trials are needed to confirm this effect on brain atrophy and determine if it can also translate to a slowing of disability progression.

Dr Lisa Melton, Head of Research at MS Research Australia said, “These trial results are a very welcome development. Treatments to slow and halt progressive MS are the greatest unmet need currently facing the MS community. MS Research Australia and our collaborators in the International Progressive MS Alliance are working hard to accelerate the development of solutions for people living with progressive MS. We can learn a lot from this trial and it brings hope that we are heading in the right direction.”

With thanks to MS Research Australia – the lead provider of research summaries on our website.