Neurofilament-light and contactin-1 association with long-term brain atrophy in natalizumab-treated relapsing-remitting multiple sclerosis

Background: Despite highly effective treatment strategies for patients with relapsing-remitting multiple sclerosis (RRMS), long-term neurodegeneration and disease progression are often considerable. Accurate blood-based biomarkers that predict long-term neurodegeneration are lacking. Objective: To assess the predictive value of serum neurofilament-light (sNfL) and serum contactin-1 (sCNTN1) for long-term magnetic resonance imaging (MRI)-derived neurodegeneration in natalizumab-treated patients with RRMS. Methods: sNfL and sCNTN1 were measured in an observational cohort of natalizumab-treated patients with RRMS at baseline (first dose) and at 3 months, Year 1, Year 2, and last follow-up (median = 5.2 years) of treatment. Disability progression was quantified using EDSS-plus criteria. Neurodegeneration was measured by calculating annualized percentage brain, ventricular, and thalamic volume change (PBVC, VVC, and TVC, respectively). Linear regression analysis was performed to identify longitudinal predictors of neurodegeneration. Results: In total, 88 patients (age = 37 +/- 9 years, 75% female) were included, of whom 48% progressed. Year 1 sNfL level (not baseline or 3 months) was associated with PBVC (standardized (std.) beta = -0.26, p = 0.013), VVC (standardized beta = 0.36, p < 0.001), and TVC (standardized beta = -0.24, p = 0.02). For sCNTN1, only 3-month level was associated with VVC (standardized beta = -0.31, p = 0.002). Conclusion: Year 1 (but not baseline) sNfL level was predictive for long-term brain atrophy in patients treated with natalizumab. sCNTN1 level did not show a clear predictive value.

Automated summary

This study found that the Year 1 sNfL level can predict long-term brain atrophy in patients treated with natalizumab for RRMS, while the sCNTN1 level did not show a clear predictive value.