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. 2025 Dec;1(4):10.1212/wn9.0000000000000040.
doi: 10.1212/wn9.0000000000000040. Epub 2025 Nov 21.

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

Alexis Novak  1 , Tucker Harvey  2 , Anna Wojdala  3 , Charlotte Teunissen  3 , Robert Fox  4
Affiliations

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

Alexis Novak et al. Neurol Open Access. 2025 Dec.

Abstract

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.

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Figures

Figure 1:
Figure 1:
Modeled change in biomarkers over time with 95% confidence intervals. Modeled change over time in serum GFAP and contactin; CSF GFAP and contactin. Red: Ibudilast; Blue: Placebo
Figure 2:
Figure 2:
Biomarkers by age for GFAP and Contactin, serum and CSF.
Figure 3:
Figure 3:
Biomarkers by sex for GFAP and Contactin, serum and CSF.
Figure 4:
Figure 4:. Correlation of serum vs CSF GFAP and serum vs CSF contactin
Correlation of serum vs CSF GFAP (A) and serum vs CSF contactin (B). Pearson correlation coefficient (r) is shown and plotted. Standard error is shaded. All time points have been represented.
See this image and copyright information in PMC

References

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