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.

Keywords: Optical coherence tomography; ibudilast; multiple sclerosis; neuroprotection.

Conflict of interest statement

Disclosures:

RB: has served as a consultant for Biogen, Genzyme, Genentech, and Novartis. He receives research support from Biogen, Genentech, and Novartis, and shares rights to intellectual property underlying the Multiple Sclerosis Performance Test, currently licensed to Qr8 Health and Biogen.

JF: The Author declares that there is no conflict of interest

PK: has received personal compensation from Carl Zeiss Medtec

CN: The Author declares that there is no conflict of interest

JS: The Author declares that there is no conflict of interest

EK: The Author declares that there is no conflict of interest

DW: The Author declares that there is no conflict of interest

JY: The Author declares that there is no conflict of interest

DE: The Author declares that there is no conflict of interest

MC: The Author declares that there is no conflict of interest

RTN: has consulted for Alexion, Alkermes, Bayer AG, Biogen, Celgene, EMD Serono, Genentech, Genzyme, Novartis, TG Therapeutics, Viela Bio.

ECK has received consulting fees from Alexion, Atlas5D, Biogen, Celgene, EMD Serono, Genentech and MedDay and research funding from AbbVie, Atlas5D, Biogen, EMD Serono, Genzyme, and Roche.

ADG: has received personal compensation for consulting from Adamas, EMD-Serono, MedDay, Greenwich Bioscience, Celgene, Teva, Sun Pharma, Novartis, Sanofi Genzyme, Genentech-Roche, Biogen, Atara, Acorda Therapeutics and received research support from Teva, Sun Pharma, Novartis, Sanofi Genzyme, Genentech-Roche, Biogen, Atara, Acorda Therapeutics.

KN has received personal licensing fee from Biogen, consulting fee from NeuroRx, and speaking fee from Sanofi Genzyme and research grant funding from Biogen, Novartis, and Sanofi Genzyme.

CSC The Author declares that there is no conflict of interest

RJF has received personal consulting fees from Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, Sanofi Gensyme, Teva, and TG therapeutics; served on advisory committees for Actelion, Biogen, Immunic, and Novartis; and received clinical trial contract and research grant funding from Novartis.

Figures

Figure 1:

Model-based change in OCT measures over time by treatment group