A comprehensive systematic review of Ibudilast as a neuroprotective therapy for progressive multiple sclerosis

Ibudilast, a phosphodiesterase inhibitor, has shown promise potential in Multiple sclerosis (MS) therapy.

This systematic review synthesizes evidence from clinical trials to assess the neuroprotective effects of ibudilast in progressive MS, focusing on brain atrophy, disability progression, and safety outcomes.

Following PRISMA 2020 guidelines, a systematic search of PubMed, Embase, Web of Science, and Scopus (1995-2025) for randomized controlled trials and prospective studies was conducted. Thirteen studies met inclusion criteria, including the phase 2 SPRINT-MS trial (n = 255). Outcomes included neuroimaging metrics (brain atrophy, lesion activity), disability progression (Expanded Disability Status Scale [EDSS]), and safety. Risk of bias was assessed using Cochrane RoB 2.0 and ROBINS-I tools.

Ibudilast significantly slowed whole-brain atrophy by 48 % versus placebo (p = 0.04), with pronounced effects in primary progressive MS (PPMS; p < 0.01). Gray matter atrophy was reduced by 35 % (p = 0.038), and thalamic integrity was preserved (p = 0.03). Retinal neurodegeneration was attenuated in PPMS (79 % reduction, p = 0.003). Chronic active lesion volume decreased by 23 % (p = 0.003), suggesting suppression of compartmentalized inflammation. No significant impact on EDSS progression or serum neurofilament light chain levels was observed.

Ibudilast demonstrates robust neuroprotection in progressive MS, particularly PPMS, with benefits on brain and retinal atrophy and chronic lesion activity.