Optical coherence tomography outcomes from SPRINT-MS, a multicenter, randomized, double-blind trial of ibudilast in progressive multiple sclerosis
Robert Bermel, Janel Fedler, Peter K. Kaiser, Cindy Novalis, Jeff Schneebaum, Elizabeth Klingner, Dawn Williams, Jon Yankey, Dixie Ecklund, Marianne Chase, Robert T. Naismith, Eric C. Klawiter, Andrew Goodman, Christopher S. Coffey, Robert J. Fox
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 mm 3 /year (−0.02693 to 0.01688) with ibudilast versus −0.03659 mm 3 /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 mm 3 /year (−0.02167, 0.020866) with ibudilast compared to −0.02083 mm 3 /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.