Targeting Neurodegeneration to Impart Neuroprotection in Progressive MS: Shiv Saidha, MBBCh

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“Patients with progressive MS who were on treatments seemed to [accumulate] atrophy at similar rates as those who were on no treatment. This tells us that a lot of these treatments that we've used don't necessarily have the desired impact at least in targeting neurodegeneration to impart neuroprotection.”

In 2018, an early analysis of the phase 2b SPRINT-MS (NCT01982942) trial revealed that ibudilast (MN-166; MediciNova) was associated with a slower progression of brain atrophy compared with placebo.¹ The trial randomized 255 patients with multiple sclerosis (MS) to ibudilast 100 mg (n = 129) or placebo (n = 126). In total, 53% of those in the ibudilast group and 52% of those in the placebo group had primary progressive MS. For those on therapy, the rate of change in brain parenchymal function was -0.0010 per year (95% CI, −0.0016 to −0.0004), compared with -0.0019 per year (95% CI, −0.0025 to −0.0013) for those given placebo, representing a between-group difference of 0.009 (95% CI, 0.00004 to 0.0017; P = .04).

In October 2020, optical coherence tomography (OCT) data from analysis of SPRINT-MS suggested that the ibudilast therapy may attenuate retinal thinning in patients with progressive MS.² The sample size of the study (n = 244) also suggested that OCT measures can be used as viable outcomes in trials of progressive disease with an appropriate treatment effect. Ibudilast, a first-in-class, orally bioavailable, small molecule macrophage migration inhibitory factor inhibitor and phosphodiesterase -4 and -10 inhibitor, slowed loss of retinal tissue compared with placebo (n = 123) in measures of peripapillary retinal nerve fiber layer thickness (P = .22), macular volume change, and ganglion cell-inner plexiform layer thickness change (P = .12).

At the 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, February 29 to March 2, Shiv Saidha, MBBCh, professor of neurology at Johns Hopkins Medicine, presented a talk on the visual system as a model for neuroprotection trials in a session on barriers in clinical trials for MS. After the session, Saidha sat down with NeurologyLive® to discuss how ibudilast differs from traditional therapies in targeting progressive MS. He spoke about the implications of the observed reduction in atrophy rates in the SPRINT MS trial as well as how promoting remyelination might offer secondary neuroprotection in patients with progressive MS.

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REFERENCES
1. Fox RJ, Coffey CS, Conwitt R, et al. Phase 2 trial of ibudilast in progressive multiple sclerosis. N Engl J Med. 2018; 379:846-855. doi: 10.1056/NEJMoa1803583.
2. Bermal RA, Felder JK, Kaiser P, et al. Optical coherence tomography outcomes from SPRINT-MS, a multicenter, randomized, double-blind trial of ibudilast in progressive multiple sclerosis. Mult Scler J. Published October 15, 2020. doi: 10.1177/1352458520964409.