MS-SPRINT has become abit of of an MS-SNAIL RACE with a One legged snail. Yep snails have a foot but MS_SPRINT took the drug of interest from the MS-SMART trial and gave us all hope to be dashed. MS-SPRINT was done years ago with Ibudilast. This was an asthma related drug approved in Japan. It was an dirty phosdiesterase 4 inhibitor. Whilst other PDE4 inhibitors have crashed and burned because their working mechanism was to block tumour necrosis factor which has repeated been shown to make MS worse. It failed to inhibit relapsing MS but seemed to inhibit progression…Yeah we say but Boo we say as that data was shown about years ago and since that time we have been drip fed of additional data from that trial. This was supported by Charity to develop a drug from pharma and sad to say I think this is not a snail but a duck and its heart has stopped beating long ago. Pharma didnt have enough dosh to develop it allowing academia to do the trial…But sadly I and you have been waiting for years for the the tiral that could help develop the drug to occur….It hasn’t so far. We have always asked what next? Without a clear plan of what is next it is hope that is the opposite of true hope. Yes I am being flippant and am disappointed. But after the positive headline we are drip fed the study. The top-line result was from 2017 so we are now 8-9 years on and if ibudilast had any sort of patent it would be 6 feet under by now…and as such I suspect ibudilast wasn’t buried with a spade. This study looks at cortical lesions and the study did not give a positive response. So my flippant title….It was a lot of hard work to get the study done and we all want them to be positive but it is important to give experience when it is not. However it shows us how hard to develop treatments without big pharma being behind it.
Krijnen EA, Bruijn AM, Eloyan A, Schoonheim MM, Fox RJ, Klawiter EC. Evaluation of cortical pathology in primary-progressive multiple sclerosis: a post hoc analysis of the SPRINT-MS trial. BMJ Neurol Open. 2026; 8(1):e001335.
Background: Multiple sclerosis (MS) involves cortical injury, including cortical lesion (CL) development. Ibudilast treatment was found to slow progression of whole brain and cortical atrophy, but the effect of ibudilast on CLs is unknown. The present study aims to evaluate the treatment effect of ibudilast on CL development and whether the effect of ibudilast on brain atrophy is modified by CLs in primary-progressive MS (PPMS).
Methods: In this longitudinal study, we analysed data of 102 people with PPMS (ibudilast: n=49; placebo: n=53) from the Secondary and Primary Progressive Ibudilast NeuroNEXT Trial in Multiple Sclerosis. CLs were identified on artificial intelligence-generated double inversion-recovery images created from T1 and T2 images at 3T MRI and rated at baseline and week 96. Atrophy was measured by cortical thickness and brain parenchymal fraction.
Results: CLs were detected in all participants with PPMS with a median count of 22 (11-34) in the ibudilast group and 28 (13-44) in the placebo group. At baseline, treatment groups did not differ in any brain volume measure or CL count. Higher CL counts at baseline were associated with higher CL formation during follow-up (B(95% CI)=0.20 (0.12 to 0.29), p<0.001), independent of ibudilast treatment.Change in CL count did not differ between treatment groups (mean difference (SD)=0.07 (0.29), p=0.364). Protective effect of ibudilast on cortical thickness was more prominent in subjects with greater CL formation, but this relationship was not observed with whole brain atrophy.
Conclusions: Ibudilast treatment does not affect CL development in PPMS. Its protective effect on cortical thinning is more prominent with greater CL formation.
COI: Noe
Disclaimer. My view
Source: multiple-sclerosis-research.org