Plasma NfL linked to cognitive processing speed in relapsing MS
Plasma neurofilament light (NfL) concentration was linked to cognitive scores in people with relapsing MS, according to phase III data SUN RAY trial of ozanimod (Zeposia) suggested.
A post-hoc analysis of SUNBEAM data showed that baseline plasma NfL, a measure of neurodegeneration, was inversely correlated with baseline Symbolic Digit Modality Test (SDMT) scores, a measure of cognitive processing speed, reported Sarah Harris, PhD, of Bristol Myers Squibb (BMS) in Princeton, New Jersey, during a poster presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Over 12 months, treatment with the sphingosine 1-phosphate receptor modulator ozanimod decreased plasma NfL and improved SDMT scores to a greater extent than interferon beta-1a (Avonex), noted Harris. .
“In the SUNBEAM trial, ozanimod showed superior benefit over interferon-beta on both cognition as measured by the SDMT and on plasma NfL as a biomarker of nerve tissue damage,” said said co-author Jeffrey Cohen, MD, of the Cleveland Clinic. MedPage Today.
“In this poster, we report that the magnitude of benefit on SDMT correlates with the amount of benefit on NfL,” Cohen said. “This indicates that the benefit on cognition was due to tissue preservation and not simply symptomatic action. Other analyzes of ozanimod on cerebral atrophy and SDMT also support this.”
In SUN RAY, people with relapsing MS were randomized to receive interferon beta-1a 30 mcg intramuscularly weekly or ozanimod 0.92 or 0.46 mg orally once daily for 12 months or longer. Plasma NfL and SDMT were assessed at baseline and at month 12.
SUNBEAM included 1,346 participants; 66% were women. At baseline, mean age was 35.6 years, time since symptom onset was 7 years, and expanded disability status scale scores were 2.6. A total of 447 people received ozanimod 0.92 mg, 451 received ozanimod 0.46 mg, and 448 received interferon beta-1a.
The SDMT is a timed test that gives participants a key that matches symbols and numbers, then presents symbols out of order and asks test takers to match them with the correct numbers. Scoring is based on the correct number of responses within 90 seconds, with higher scores indicating faster processing. A change of 4 points is considered clinically significant, Harris noted.
At baseline, the median plasma NfL was 14.7 pg/mL and the SDMT score was 48.0. Kendall’s τ correlation between these variables was -0.10 (95% CI -0.14 to -0.06), indicating a slight negative association.
Treatment changes were assessed by linear regression and bootstrap sampling stratified by treatment. Based on 1,000 bootstrap samples, greater median percent reduction in plasma NfL was associated with greater mean change in SDMT from baseline at month 12, Harris and colleagues reported.
Both doses of ozanimod were associated with greater median reductions in plasma NfL and mean improvements in SDMT than interferon beta-1a, with the 0.92 mg dose showing the greatest differences.
“Ozanimod 0.92 mg was associated with greater reductions in plasma NfL concentration (nominal PP=0.0019 based on regression models),” Harris and colleagues wrote.
The analysis is exploratory, the researchers acknowledged. “Future prospective analyzes are warranted to determine the clinical utility of plasma NfL concentration as a marker of cognitive processing speed,” they noted.
The analysis was supported by BMS. Harris is a shareholder of BMS.
Cohen has disclosed his relationships with Biogen, BMS, Convelo, Genentech, Janssen, NervGen, Novartis, PSI and H3 Communications and served as editor of Multiple Sclerosis Journal.