Ibudilast slows grey matter and whole brain atrophy but has no impact on brain lesion counts in primary or secondary progressive MS, new results from the anti-inflammatory agent show.
A secondary analysis of the 2018 SPRINT-MS study, which compared ibudilast with placebo over 96 weeks, found a 35% treatment effect on grey matter atrophy with the phosphodiesterase (PDE) inhibitor.
The study, published in Neurology, found whole brain atrophy was reduced by 20% with ibudilast.
New or enlarging T2 hyperintense lesions were similar in both the treated and control groups (37.2% v 39.0%).
“Adjusting for disease subtype and use of injectable disease-modifying therapy, no difference was noted for the change in T2 lesion volume with ibudilast,” the study said.
T1 hypointense lesions were numerically higher but statistically similar in both groups (33.3% v 23.5%) and again, there was no difference in lesion volume.
“Similar to its counterpart phase 2 study in relapsing MS, ibudilast demonstrated no effect in reducing N/E T2 lesion count or volume in the current progressive MS study.”
“This suggests the mechanisms of action of the drug exert neuroprotective effects aside from overt anti-inflammatory effects. This also suggests that the reduction in whole brain and grey matter atrophy does not simply reflect a subsequent effect of reducing white matter lesion formation.”
An accompanying editorial said the findings confirm the lack of effect of ibudilast on inflammation as reported in the previous trial in relapsing-remitting MS.
However the finding of no treatment effect on T1 hypointensities in the current study was in contrast to that of the RRMS study.
“… relapses may produce a measurable and sustained effect on disability; therefore, the mechanisms of disability worsening between relapsing-remitting MS and progressive MS may be different and somehow favour the impact of ibudilast on progression in the relapsing group,” the editorial said.
“At present, a number of disease-modifying treatments with remarkable anti-inflammatory effects are already available, whereas drugs that can tackle predominantly neurodegeneration are virtually absent.”
“The key question then is, do neuroprotective drugs provide a valuable option for MS treatment, both in the relapsing-remitting phase, probably added to an anti-inflammatory agent, and particularly in the progressive phase, when neurodegeneration plays a major role?”
It said large and robust phase 3 studies were required.
Commenting on the study for the limbic, Professor Simon Broadley said the data in relation to atrophy was very encouraging and hinted at a genuine “neuroprotective” effect that is unrelated to acute inflammation/lesions.
“So, it is certainly a promising avenue that requires further study. However, the study was negative in terms of the clinical endpoints. Of course it was not powered to look at this, but even so there really was nothing positive on the clinical front.”
Professor Broadley, from Griffith University and the Gold Coast University Hospital, said measuring brain atrophy was difficult.
“…there is a lot of natural/technical variability that can give rise to spurious results in smaller studies and it is conceivable that a therapy might cause “brain swelling” which could offset any real atrophy, making it look like it is protective when it is not.”
He said the opposite of this – pseudoatrophy – had been observed with some of the more potent immunotherapies.