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.