Effect of Ibudilast vs Placebo on GFAP and Contactin levels in a phase 2 clinical trial in progressive multiple sclerosis.

OBJECTIVE

To evaluate GFAP and contactin as potential treatment response biomarkers in progressive MS.

METHODS

The SPRINT-MS trial utilized the NeuroNEXT network to enroll people with progressive MS, age 18-65 years, with evidence of progression in the past two years. Participants were randomized 1:1 and followed over two years. Serum and CSF were analyzed for GFAP and contactin. Mixed-effects models examined the longitudinal changes in biomarker and the effect of ibudilast treatment.

RESULTS

246 participants (mean age 56 yrs; 53% female) were included. There was no effect of ibudilast treatment on the rate of change of either GFAP or contactin in either serum or CSF (p>0.3 for all comparisons). Serum GFAP increased over time (14.4 pg/ml over 96 weeks; p=0.008), while CSF GFAP levels remained stable. Contactin didn't change significantly over the course of follow-up in either serum or CSF. Both age and sex affected GFAP and contactin levels.

DISCUSSION: We found that although ibudilast treatment previously was associated with positive effects on MRI measures of MS disease, it didn't affect GFAP or contactin. The generalizability of these findings regarding the utility of GFAP or contactin as a treatment response biomarker in progressive MS requires further study.Registered on ClinicalTrials.gov: NCT01982942.