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

Abstract

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.

• Authors: Robert J Fox, Paola Raska, Christian Barro, Matthew Karafa, Victoria Konig, Robert A Bermel, Marianne Chase, Christopher S Coffey, Andrew D Goodman, Eric C Klawiter, Robert T Naismith, Jens Kuhle
• Journal: Multiple sclerosis (Houndmills, Basingstoke, England) (Mult Scler) Vol. 27 Issue 13 Pg. 2014-2022 (11 2021) ISSN: 1477-0970 [Electronic] England
• PMID: 33635141 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Neurofilament Proteins
• Pyridines
• ibudilast

Topics

• Biomarkers
• Humans
• Intermediate Filaments
• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive (drug therapy)
• Neurofilament Proteins
• Pyridines