Plasma neurofilament light (NfL) concentration was tied to cognitive scores in people with relapsing MS, data from the phase III SUNBEAM trial of ozanimod (Zeposia) suggested.
A post hoc analysis of SUNBEAM data showed that baseline plasma NfL, a measure of neurodegeneration, correlated inversely with baseline scores on the Symbol Digit Modalities Test (SDMT), a measure of cognitive processing speed, reported Sarah Harris, PhD, of Bristol Myers Squibb (BMS) in Princeton, New Jersey, in a poster presentation at the Consortium of Multiple Sclerosis Centers annual meeting.
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), Harris noted.
“In the SUNBEAM trial, ozanimod showed superior benefit compared to interferon-beta on both cognition measured by the SDMT and on plasma NfL as a biomarker of nervous tissue damage,” co-author Jeffrey Cohen, MD, of the Cleveland Clinic, told MedPage Today.
“In this poster, we report that the magnitude of benefit on SDMT correlated with the amount of benefit on NfL,” Cohen said. “This indicates that the benefit on cognition was due to preservation of tissue and not merely a symptomatic action. Other analyses of ozanimod on brain atrophy and SDMT support this, also.”
In SUNBEAM, people with relapsing MS were randomized to weekly intramuscular interferon beta-1a 30 µg or once-daily oral ozanimod 0.92 or 0.46 mg for 12 months or longer. Plasma NfL and SDMT were assessed at baseline and month 12.
SUNBEAM included 1,346 participants; 66% were women. At baseline, mean age was 35.6, time from 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 pairs symbols and numerals, then presents symbols out of sequence and asks test-takers to match them with the correct numerals. Scoring is based on the correct number of responses in 90 seconds, with higher scores indicating faster processing. A 4-point change is considered clinically meaningful, Harris noted.
At baseline, median plasma NfL was 14.7 pg/mL and 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.
Changes on treatment were evaluated with linear regression and treatment-stratified bootstrap sampling. Based on 1,000 bootstrap samples, a greater median percent reduction in plasma NfL was associated with greater mean SDMT change from baseline at month 12, Harris and colleagues reported.
Both ozanimod doses 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 P< 0.0001 based on robust linear models) and improvements in SDMT score than interferon beta-1a (nominal P=0.0019 based on regression models),” Harris and colleagues wrote.
The analysis is exploratory, the researchers acknowledged. “Future prospective analyses 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 BMS shareholder.
Cohen dislcosed relationships with Biogen, BMS, Convelo, Genentech, Janssen, NervGen, Novartis, PSI, and H3 Communications and serving as an editor of Multiple Sclerosis Journal.