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

Tjalf Ziemssen, Douglas L. Arnold, Enrique Alvarez, Anne H. Cross, Roman Willi, Bingbing Li, Petra Kukkaro, Harald Kropshofer, Krishnan Ramanathan, Martin Merschhemke, Bernd Kieseier, Wendy Su, Dieter A. Häring, Stephen L. Hauser, Ludwig Kappos, Jens Kuhle

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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 post-hoc studies suggested that sNfL could be a prognostic biomarker in RMS. In the phase 3 ASCLEPIOS I/II trials in which ofatumumab demonstrated better efficacy outcomes than teriflunomide, treatment with ofatumumab also led to significantly reduced sNfL levels compared to teriflunomide treatment. 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 (>median) 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<0.001), 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<0.001), 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.

Original languageEnglish
Article number852563
JournalFrontiers in immunology
Volume13
DOIs
StatePublished - Mar 31 2022

Keywords

  • MS disease activity
  • brain atrophy
  • lesion formation
  • prognostic biomarker
  • serum neurofilament light chain

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