It is not uncommon within the pharmaceutical industry to find that a drug originally developed to treat one disease may coincidentally have beneficial effects on another – sometimes referred to as “repurposing”. Ibudilast is one such drug. Commonly prescribed in Japan for the treatment of asthma and stroke, Ibudilast is currently being investigated as a potential treatment in progressive forms of MS.
In a recent controlled trial from the United States published in the “New England Journal of Medicine”, researchers took 255 people with primary or secondary progressive MS (PPMS or SPMS) and gave them either ibudilast or placebo for 96 weeks. They were followed up with MRI scans and clinical assessments to assess rates of brain atrophy and disability progression.
Approximately half of the people in each group had PPMS and half had SPMS, and the team designed the trial in such a way as to have very similar populations in each group. They ranged from 21-65 years, had EDSS scores of 3.0 to 6.5 and had evidence of disability progression in the preceding 2 years. So at the end of the study period, what did the results show? Well those people in the ibudilast group had nearly half the amount of brain-tissue loss (shrinkage) than those in the placebo group. There was also a trend towards less disability progression in the treatment group.
In terms of side effects and adverse events, ibudilast has been safely used in Japan for many years and in this study also appeared safe, with the most commonly reported side effects being gastrointestinal symptoms (nausea, diarrhoea, abdominal pain, vomiting) and depression. Interestingly, serious adverse events were actually more frequent in the placebo group (16 vs. 19%). The percentage of patients who withdrew from the trial was 16% with ibudilast and 11% with placebo.
So why are these results potentially so significant? It is normal for our brains to gradually shrink as we age, but unfortunately this is up to 3 times quicker in people with MS. Brain shrinkage is important in MS because it is felt to correlate strongly with progression of disability. The theory is that if you can slow the rate of brain shrinkage and therefore the loss of brain cells, then you should also slow the rate of disability progression.
The investigators involved in this study state that further trials are now needed to ensure that their findings are reproducible, but also to examine the long-term effects of ibudilast on slowing disability progression.
This is an exciting development in an area of MS where successful treatments have been sorely lacking. We in the OMS community, particularly those with progressive forms of MS, some of whom are having difficulty stabilising the illness, should be heartened by these findings. We eagerly await further evidence. It is also worth noting that there is already an ongoing trial in the UK (MS-STAT2) assessing if simvastatin (a commonly prescribed treatment to lower cholesterol) has an effect on disability progression, having already demonstrated a similar effect on slowing brain shrinkage as ibudilast. Above all, both drugs are relatively safe and well tolerated and may become important new medication choices for those with progressive MS. Watch this space…
Dr Jonathan White MBChB MRCOG
N Engl J Med 2018;379:846-55. DOI: 10.1056/NEJMoa1803583 https://doi.org/10.1016/j.jns.2015.07.014 https://www.mssociety.org.uk/research/explore-our-research/research-we-fund/search-our-research-projects/could-simvastatin-be-a-treatment-for-secondary-progressive-ms