Neurofilament light chain in a phase 2 clinical trial of ibudilast in progressive multiple sclerosis

Background: Sensitive and specific biomarkers for use in progressive multiple sclerosis (MS) have not been established. We investigate neurofilament light (NfL) as a treatment response biomarker in progressive MS. Objective: To evaluate whether ibudilast 100 mg/day alters serum and cerebrospinal fluid (CSF) levels of NfL in progressive MS. Methods: In a protocol-defined exploratory analysis from a 2-year, phase 2 clinical trial of ibudilast in progressive MS (NCT01982942), serum samples were collected from 239 subjects and a subset contributed CSF and assayed using single-molecule assay (SIMOA) immunoassay. A mixed model for repeated measurements yielded log(NfL) as the response variable. Results: The geometric mean baseline serum NfL was 31.9 and 28.8 pg/mL in placebo and ibudilast groups, respectively. The geometric mean baseline CSF NfL was 1150.8 and 1290.3 pg/mL in placebo and ibudilast groups, respectively. Serum and CSF NfL correlations were r = 0.52 and r = 0.78 at weeks 48 and 96, respectively. Over 96 weeks, there was no between-group difference in NfL in either serum (p = 0.76) or CSF (p = 0.46). After controlling for factors that may affect NfL, no effect of ibudilast on NfL in either serum or CSF was observed. Conclusion: Ibudilast treatment was not associated with a change in either serum or CSF NfL.

Automated summary

This study aimed to evaluate the effect of ibudilast treatment on serum and cerebrospinal fluid (CSF) levels of neurofilament light (NfL) in progressive multiple sclerosis (MS). The results showed no significant difference in NfL levels in either serum or CSF between the treatment and placebo groups.