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Serum Neurofilament Levels and PML Risk in Patients With Multiple Sclerosis Treated With Natalizumab
Nicolás Fissolo1, Beatrice Pignolet1, Jordi Rio1
1From the Servei de Neurologia-Neuroimmunologia (N.F., M.C.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse (B.P., D.B.), CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France; Servei de Neurologia-Neuroimmunologia (J.R., X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Univ. Lille (P.V.), Inserm U1172, CHU Lille, FHU Imminent, France; Université (A.R.), Bordeaux; CHU de Bordeaux (A.R.), INSERM-CHU CIC-P 0005, & Services de Neurologie; Neurocentre Magendie (A.R.), INSERM U1215; Department of Neurology (J.dS), Hôpital Civil, Strasbourg; Department of Neurology (P.L.), CHU Montpellier; Department of Neurology CHU Lyon (S.V.); Department of Neurology (C.P.), Hôpital de la Salpétrière, Paris; Chi Aix en Provence (L.M.-A.); Department of Neurology and Faculté de Médecine de Reims (A.T.), CHU de Reims, URCA; LPN EA2027 Université Paris VIII (A.T.), Saint-Denis; Department of Neurology (P.C.), CHRU Clermont Ferrand; Department of Neurology (T.M.), CHU Dijon; Aix-Marseille Univ (J.P.), APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, CNRS, CRMBM UMR 7339, Marseille; Service de Neurology (C.L.-F.), CHU de Nice Pasteur2, Université Nice Cote d'Azur UR2CA URRIS, Nice; Neurologie (B.B.), CHU Rouen; and Neurologie (G.D.), CHU Caen, France.
Serum neurofilament light chain (NFL) levels can predict progressive multifocal leukoencephalopathy (PML) risk in multiple sclerosis (MS) patients treated with natalizumab (NTZ). Elevated NFL levels also help differentiate PML from MS relapses.
Area of Science:
- Neuroscience
- Immunology
- Biomarker Discovery
Background:
- Natalizumab (NTZ) is an effective treatment for multiple sclerosis (MS).
- Progressive multifocal leukoencephalopathy (PML) is a rare but serious opportunistic infection associated with NTZ therapy.
- Predictive biomarkers are needed to identify MS patients at high risk for PML.
Purpose of the Study:
- To evaluate serum neurofilament light chain (NFL) levels as a predictor of PML risk in NTZ-treated MS patients.
- To assess the utility of serum NFL levels in differentiating PML from MS relapses.
Main Methods:
- Serum NFL levels were measured using single molecule array (Simoa) across four distinct patient cohorts.
- Cohorts included prospective pre-PML and non-PML NTZ-treated MS patients, patients during active PML, a replication cohort, and patients during exacerbations.
Main Results:
- Serum NFL levels were significantly elevated in pre-PML patients compared to controls after two years of NTZ treatment.
- Serum NFL levels demonstrated prognostic performance for PML development, consistent across independent cohorts.
- Serum NFL levels were substantially higher during PML compared to MS relapses, aiding in differential diagnosis.
Conclusions:
- Serum NFL levels serve as a valuable biomarker for identifying NTZ-treated MS patients at increased risk of developing PML.
- Serum NFL measurements can effectively distinguish PML from MS relapses in clinical practice.
- These findings support the integration of serum NFL testing into routine monitoring for NTZ-treated MS patients.
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