Serum neurofilament light-chain (sNfL) is associated with disease activity and tissue damage, predicts long-term outcomes, and is reduced by disease-modifying therapies in RRMS patients.
In a post hoc analysis, determine sNfL differences from baseline (BL) to 48 months and associations with long-term clinical outcomes in patients treated with intramuscular (IM) interferon (IFN) beta-1a, glatiramer acetate (GA), or both therapies (IFN+GA).
CombiRx was a placebo (PLB)-controlled double-blind phase 3 trial in treatment-naive RRMS patients randomized to IM IFN beta-1a 30 µg weekly+PLB, GA 20 mg/mL daily+PLB, or IFN+GA treatment for up to 7 years. Samples for biomarker analysis were collected at BL, 6, 12, 36, and 48 months from volunteers for a substudy offered in most sites. Relapses and Expanded Disability Status Scale (EDSS) scores were collected every 3 months. A Simoa Human Neurology 4-Plex A assay analysed sNfL levels. A linear mixed model compared sNfL values over time adjusted for BL EDSS, age, sex and body mass index (BMI). A Cox regression model with the same covariates analysed BL sNfL as a predictor of relapse.
Samples were collected from 159 IFN, 172 GA, and 344 IFN+GA patients. BL characteristics were generally well balanced, including mean age, sex, mean BMI, mean time since symptom and diagnosis onset, and mean EDSS scores. Significant reductions relative to BL in sNfL levels were seen at 6, 12 and 36 months in the IFN, GA, and IFN+GA treatment groups. BL sNfL ≥16 pg/mL significantly predicted relapse within 90 days (hazard ratio [HR]: 2.25, P=0.0041), 180 days (HR: 1.67, P=0.0130) and 1 year from BL (HR: 1.40, P=0.0435), but not over the entire study duration (HR: 1.08, P=0.5596). In patients with BL sNfL ≥16 pg/mL and ≥1 BL gadolinium-enhancing (Gd+) lesion, a significantly higher percentage (16.8%) relapsed within 90 days than in patients with BL sNfL ≥16 pg/mL and no BL Gd+ lesions (9.2%), or BL sNfL <16 pg/mL with (7.3%) or without BL Gd+ lesions (6.7%) (P=0.0051).
Treatment with IFN, GA, and IFN+GA significantly reduced sNfL levels within 6 months and was maintained over 36 months. Results suggest that BL sNfL levels predict relapses within 1 year, and that the combination of lesion activity and sNfL is a stronger predictor of relapse than either one alone.
This analysis was funded by Biogen. Biogen also funded the writing support for this abstract, which was provided by Ashfield Healthcare Communications (Middletown, CT, USA).