Prognostic value of serum neurofilament light chain for disease activity and worsening in patients with relapsing multiple sclerosis: Results from the phase 3 ASCLEPIOS I and II trials

Abstract

OBJECTIVE: This study aims to confirm the prognostic value of baseline serum neurofilament light chain (sNfL) for on-study disease activity and worsening in patients with relapsing MS (RMS). BACKGROUND: Previous DESIGN/METHODS: In this study, we report protocol-planned analyses from the pooled ASCLEPIOS I/II trials (N=1882). Per protocol, patients were stratified by median baseline sNfL levels (9.3 pg/ml) into high (\u3emedian) and low (≤median) categories to prognosticate: annualized rate of new/enlarging T2 (neT2) lesions in year 1 and 2, annualized relapse rate, annual percentage change in whole brain (WB) and regional brain volume [thalamus, white matter (WM), cortical gray matter (cGM)], and disability outcomes. Similar analyses were performed for the recently diagnosed (within 3 years), treatment-naive patients (no prior disease-modifying therapy) subgroup. RESULTS: High versus low sNfL at baseline was prognostic of increased on-study T2 lesion formation at year 1 (relative increase: ofatumumab +158%; teriflunomide +69%, both p\u3c0.001), which persisted in year 2 (+65%, p=0.124; +46%, p=0.003); of higher annual percentage change of WB volume (ofatumumab, -0.32% vs. -0.24%, p=0.044, and teriflunomide, -0.43% vs. -0.29%, p=0.002), thalamic volume (-0.56% vs. -0.31%, p=0.047 and -0.94% vs. -0.49%, p\u3c0.001), and WM volume (-0.30% vs. -0.19%, p=0.083 and -0.38% vs. -0.18%, p=0.003) but not of cGM volume (-0.39% vs. -0.32%, p=0.337 and -0.49% vs. -0.46%, p=0.563). A single sNfL assessment at baseline was not prognostic for on-study relapses or disability worsening. Results were similar in the subgroup of recently diagnosed, treatment-naive patients. CONCLUSION: This study confirms that baseline sNfL levels are prognostic of future on-study lesion formation and whole brain and regional atrophy in all RMS patients, including recently diagnosed, treatment-naive patients