Abstract Details

Title Effect of Ibudilast on Neurofilament-light Chain in Progressive MS: Analysis from a Phase II Trial

Topic Multiple Sclerosis

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-033

Objective To report the effect of ibudilast on serum and CSF neurofilament-light (NfL) from the phase II trial of ibudilast in progressive MS.

Background Serum NfL is a candidate biomarker of treatment response in multiple sclerosis (MS) clinical trials. Ibudilast 100 mg/d was found to slow the progression of brain atrophy in SPRINT-MS, a 255-patient randomized, placebo-controlled 96-week phase II trial of progressive MS. We evaluated the effect of ibudilast on serum and CSF NfL in SPRINT-MS.

Design/Methods Serum samples were collected at screening, 8, 48, and 96 weeks. In an optional sub-study, 75 patients consented to CSF sampling, which was collected at screening, 48, and 96 weeks. NfL was assayed using the SIMOA immunoassay. Analysis utilized a mixed model for repeated measurements with log(NFL) as the response variable and adjusted for treatment, age and log(baseline NFL). The model further included visit-by-treatment and visit-by-log (baseline NFL) interactions, using an AR(1) covariance matrix. Analysis was according to intent-to-treat (ITT) and included all available values in the statistical analysis.

Results Mean baseline serum NfL was 33.5+22.4 and 40.3+54.1 pg/ml in ibudilast and placebo groups, respectively. Mean baseline CSF NfL was 1616.7+1474.4 and 1301.2+822.2 pg/ml in ibudilast and placebo groups, respectively. Over the course of the study, there was no between-group difference in NfL in either serum (P=0.35) or CSF (P=0.62). In some subjects, changes in NfL were observed concomitantly with new/enlarging T2 lesions, which suggests confounding by active inflammation.

Conclusions Ibudilast treatment was not associated with a decline in either serum or CSF NfL. Inflammatory activity may have confounded the intended use of NfL to measure neurodegeneration.

Authors/Disclosures
Robert J. Fox, MD, FAAN (Cleveland Clinic) PRESENTER	Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AB Science. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Immunic. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siemens. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astoria Biologica. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for InnoCare Pharma. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AB Science. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BMS. The institution of Dr. Fox has received research support from National Institutes of Health. The institution of Dr. Fox has received research support from National MS Society. Dr. Fox has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Christian Barro, MD, PhD (Brigham and Women's Hospital)	Dr. Barro has nothing to disclose.
Robert A. Bermel, MD, FAAN (Cleveland Clinic)	Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi/Genzyme. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech/Roche. Dr. Bermel has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Bermel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Bermel has received research support from Biogen. The institution of Dr. Bermel has received research support from Roche. The institution of Dr. Bermel has received research support from Novartis. Dr. Bermel has received intellectual property interests from a discovery or technology relating to health care.
Christopher Coffey, PhD, FAAN (University of Iowa)	Dr. Coffey has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association. The institution of Dr. Coffey has received research support from NIH. The institution of Dr. Coffey has received research support from Michael J Fox Foundation.
Andrew D. Goodman, MD, FAAN (University of Rochester Dept. Neurology)	Dr. Goodman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Swan Bio. Dr. Goodman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Goodman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Goodman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Goodman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Goodman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Goodman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for IMCYSE. Dr. Goodman has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Pfizer. The institution of Dr. Goodman has received research support from Atara. The institution of Dr. Goodman has received research support from Genzyme. The institution of Dr. Goodman has received research support from EMD-Serono.
Eric Klawiter, MD, FAAN (Massachusetts General Hospital)	Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Galen/Atlantica. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Banner Life Sciences. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Greenwich Biosciences. Dr. Klawiter has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for OM1. Dr. Klawiter has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. The institution of Dr. Klawiter has received research support from Biogen. The institution of Dr. Klawiter has received research support from Abbvie. The institution of Dr. Klawiter has received research support from Genentech.
Kazuko Matsuda, MD (Medcinova)	No disclosure on file
Robert T. Naismith, MD, FAAN (Washington University)	Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squib. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Naismith has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Genzyme. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celltrion. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astoria. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Impaact-Bio. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kyverna. Dr. Naismith has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon. Dr. Naismith has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for NEJM Journal Watch.
Jens Kuhle, MD	Dr. Kuhle has nothing to disclose.
	No disclosure on file

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