Ibudilast slows brain shrinkage in progressive multiple sclerosis patients
medwireNews: Ibudilast may slow brain atrophy in patients with progressive multiple sclerosis, show findings from a phase II study.
The drug, which inhibits cyclic nucleotide phosphodiesterases, macrophage migratory inhibitory factor and toll-like receptor 4, can cross the blood–brain barrier; and when compared with placebo in progressive multiple sclerosis, the average difference in brain atrophy over a 96-week period was 0.0009 units per year in favour of ibudilast.
This “represents approximately 2.5 ml less brain-tissue loss with ibudilast than with placebo […] and a relative difference of 48%”, report the NN102/SPRINT-MS Trial Investigators.
Robert Fox (Cleveland Clinic, Ohio, USA) and team say that this finding “can be broadly compared” with other trial results reporting a 17.5% slowing of brain atrophy with ocrelizumab, 15.0% with siponimod and 43.0% with simvastatin.
But they caution that as direct comparisons were not made with these drugs in the current trial, no conclusions about the relative effects on brain atrophy can be made.
As reported in The New England Journal of Medicine, 255 multiple sclerosis patients were randomly assigned to receive ibudilast or placebo for 96 weeks. Around half of patients in each group had primary progressive multiple sclerosis, while the remainder had secondary progressive disease.
The 129 patients in the ibudilast group received a daily oral dose of 100 mg after an initial 2 weeks at 60 mg. Dose adjustments between 60 and 100 mg were allowed up to week 8, after which the then-current dose was maintained.
The patients’ brain parenchymal fraction decreased at an average rate of 0.0010 units per year among those taking ibudilast versus 0.0019 among those taking placebo.
The researchers note, however, that the decline in disability progression was similar between the two groups. This was the also the case for the other secondary endpoints, including transverse and longitudinal diffusivity in corticospinal tracts and retinal nerve fibre layer thickness. The only exceptions were cortical thickness and magnetisation transfer ratio in normal-appearing brain tissue, for which the annual rate of change was significantly smaller with ibudilast than placebo.
But the researchers note that these secondary analyses were not adjusted for multiple comparisons, limiting their interpretation.
There was no significant difference in the rate of adverse events between patients taking ibudilast and those taking placebo, at 92% versus 88%, respectively, but there was a higher incidence of gastrointestinal symptoms, including nausea, diarrhoea, abdominal pain and vomiting, and depression in the ibudilast group than the placebo group. The serious adverse event rates were 16% and 19%, respectively, and a corresponding 8% and 4% withdrew due to adverse events.
The investigators conclude that “[f]urther trials are needed to identify whether the effect on brain atrophy is reproducible and is associated with slowed progression of neurologic disability.”
By Lucy Piper
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