Dataset Information

Optical coherence tomography outcomes from SPRINT-MS, a multicenter, randomized, double-blind trial of ibudilast in progressive multiple sclerosis.

ABSTRACT:

Background

The SPRINT-MS trial demonstrated benefit of ibudilast on brain atrophy over 96 weeks in progressive multiple sclerosis (MS). Optical coherence tomography (OCT) was performed in all trial participants.

Objective

Report the OCT results of the SPRINT-MS trial.

Methods

OCT was obtained at baseline and every 6 months using spectral domain OCT and analyzed by an OCT reading center. Change in each OCT outcome measure by treatment group was estimated using linear mixed models.

Results

Change in pRNFL thickness was +0.0424 uM/year (95% confidence interval (CI): -0.3091 to 0.3939) for ibudilast versus -0.2630 uM (95% CI: -0.5973 to 0.0714) for placebo (n = 244, p = 0.22). Macular volume change was -0.00503 mm³/year (-0.02693 to 0.01688) with ibudilast versus -0.03659 mm³/year (-0.05824 to -0.01494) for placebo in the Spectralis cohort (n = 61, p = 0.044). For the Cirrus cohort, macular volume change was -0.00040 mm³/year (-0.02167, 0.020866) with ibudilast compared to -0.02083 mm³/year (-0.04134 to -0.00033) for placebo (n = 183, p = 0.1734). Ganglion cell-inner plexiform layer thickness change, available from Cirrus, was -0.4893 uM/year (-0.9132, -0.0654) with ibudilast versus -0.9587 uM/year (-1.3677, -0.5498) with placebo (n = 183, p = 0.12).

Conclusion

Retinal thinning in MS may be attenuated by ibudilast. Sample size estimates suggest OCT can be a viable outcome measure in progressive MS trials if a therapy has a large treatment effect.

Trial registration

NN102/SPRINT-MS ClinicalTrials.gov number, NCT01982942.

SUBMITTER: Bermel RA

PROVIDER: S-EPMC8046841 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:There are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis. METHODS:We enrolled patients with primary or secondary progressive multiple sclerosis in a phase 2 randomized trial of oral ibudilast (?100 mg daily) or placebo for 96 weeks. The primary efficacy end point was the rate of brain atrophy, as measured by the brain parenchymal fraction (brain size relative to the volume of the outer surface contour of the brain). Major secondary end points included the change in the pyramidal tracts on diffusion tensor imaging, the magnetization transfer ratio in normal-appearing brain tissue, the thickness of the retinal nerve-fiber layer, and cortical atrophy, all measures of tissue damage in multiple sclerosis. RESULTS:Of 255 patients who underwent randomization, 129 were assigned to ibudilast and 126 to placebo. A total of 53% of the patients in the ibudilast group and 52% of those in the placebo group had primary progressive disease; the others had secondary progressive disease. The rate of change in the brain parenchymal fraction was -0.0010 per year with ibudilast and -0.0019 per year with placebo (difference, 0.0009; 95% confidence interval, 0.00004 to 0.0017; P=0.04), which represents approximately 2.5 ml less brain-tissue loss with ibudilast over a period of 96 weeks. Adverse events with ibudilast included gastrointestinal symptoms, headache, and depression. CONCLUSIONS:In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression. (Funded by the National Institute of Neurological Disorders and Stroke and others; NN102/SPRINT-MS ClinicalTrials.gov number, NCT01982942 .).