1. Serum Neurofilament Levels and PML Risk in Patients With Multiple Sclerosis Treated With Natalizumab
- Author
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Fissolo, Nicolás, Pignolet, Beatrice, Rio, Jordi, Vermersch, Patrick, Ruet, Aurélie, deSèze, Jerome, Labauge, Pierre, Vukusic, Sandra, Papeix, Caroline, Martinez-Almoyna, Laurent, Tourbah, Ayman, Clavelou, Pierre, Moreau, Thibault, Pelletier, Jean, Lebrun-Frenay, Christine, Bourre, Bertrand, Defer, Gilles, Montalban, Xavier, Brassat, David, Comabella, Manuel, Universitat Autònoma de Barcelona, Universitat Autònoma de Barcelona (UAB), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Vall d'Hebron University Hospital [Barcelona], Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [Aix-en-Provence], Centre Hospitalier du Pays d'Aix, Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire de Psychopathologie et Neuropsychologie (LPN), Université Paris 8 Vincennes-Saint-Denis (UP8), CHU Clermont-Ferrand, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire de Nice (CHU Nice), Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), CHU Rouen, Normandie Université (NU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre d'Esclerosi Múltiple de Catalunya (CemCat), Vall d’Hebron Research Institute (VHIR), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Lille Neurosciences & Cognition - U 1172 (LilNCog), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), CHU Bordeaux [Bordeaux], Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Service de Neurologie [Lyon], CHU Lyon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de neurologie [Reims], Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Service de neurologie [Rouen], Normandie Université (NU)-Normandie Université (NU), Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), HAL-SU, Gestionnaire, Institut Català de la Salut, [Fissolo N, Comabella M] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Pignolet B] CRC-SEP Neurosciences Centre Hospitalier Universitaire Toulouse, CPTP INSERM UMR 1043 CNRS UMR 5282 et Université de Toulouse III, UPS, France. [Rio J, Montalban X] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Vermersch P] Univ. Lille, Inserm U1172, CHU Lille, FHU Imminent, France. [Ruet A] CHU de Bordeaux, INSERM-CHU CIC-P 0005, Service de Neurologie, Bordeaux F-33076, France. Université de Bordeaux, Bordeaux F-33076, France. [deSèze J] Department of Neurology, Hôpital Civil, Strasbourg, Vall d'Hebron Barcelona Hospital Campus, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
- Subjects
Male ,Oncology ,Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::Neurofilament Proteins [CHEMICALS AND DRUGS] ,viruses ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,MESH: Multiple Sclerosis, Relapsing-Remitting / blood ,0302 clinical medicine ,Natalizumab ,Neurofilament Proteins ,030212 general & internal medicine ,Prospective cohort study ,MESH: Middle Aged ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Progressive multifocal leukoencephalopathy ,Leukoencephalopathy, Progressive Multifocal ,Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES] ,MESH: Multiple Sclerosis / diagnosis ,virus diseases ,MESH: Follow-Up Studies ,Middle Aged ,Prognosis ,Clinical Practice ,MESH: Immunologic Factors / administration & dosage ,Neurology ,MESH: Young Adult ,enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES] ,Cohort ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,Female ,MESH: Multiple Sclerosis / drug therapy ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Otros calificadores::Otros calificadores::Otros calificadores::/sangre [Otros calificadores] ,medicine.drug ,Adult ,medicine.medical_specialty ,Neurofilament ,MESH: Multiple Sclerosis, Relapsing-Remitting / diagnosis ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Filaments citoplasmàtics ,sustancias macromoleculares::polímeros::biopolímeros::proteínas de filamentos intermedios::proteínas de neurofilamentos [COMPUESTOS QUÍMICOS Y DROGAS] ,Sensitivity and Specificity ,Article ,MESH: Prognosis ,Multiple sclerosis ,Young Adult ,03 medical and health sciences ,Multiple Sclerosis, Relapsing-Remitting ,Internal medicine ,parasitic diseases ,MESH: Leukoencephalopathy, Progressive Multifocal / blood ,medicine ,Humans ,Immunologic Factors ,Other subheadings::Other subheadings::/blood [Other subheadings] ,In patient ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,MESH: Leukoencephalopathy, Progressive Multifocal / diagnosis ,MESH: Humans ,business.industry ,MESH: Multiple Sclerosis / blood ,MESH: Adult ,medicine.disease ,MESH: Sensitivity and Specificity ,MESH: Male ,Class I ,Avaluació de resultats (Assistència sanitària) ,MESH: Multiple Sclerosis, Relapsing-Remitting / drug therapy ,Neurology (clinical) ,business ,Esclerosi múltiple - Tractament ,MESH: Female ,MESH: Natalizumab / administration & dosage ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,030217 neurology & neurosurgery ,Follow-Up Studies ,MESH: Neurofilament Proteins / blood - Abstract
ObjectivesThe study aimed to assess the potential for serum neurofilament light chain (NFL) levels to predict the risk of progressive multifocal leukoencephalopathy (PML) in natalizumab (NTZ)-treated patients with multiple sclerosis (MS) and to discriminate PML from MS relapses.MethodsNFL levels were measured with single molecule array (Simoa) in 4 cohorts: (1) a prospective cohort of patients with MS who developed PML under NTZ therapy (pre-PML) and non-PML NTZ-treated patients (NTZ-ctr); (2) a cohort of patients whose blood was collected during PML; (3) an independent cohort of non-PML NTZ-treated patients with serum NFL determinations at 2 years (replication cohort); and (4) a cohort of patients whose blood was collected during exacerbations.ResultsSerum NFL levels were significantly increased after 2 years of NTZ treatment in pre-PML patients compared with NTZ-ctr. The prognostic performance of serum NFL levels to predict PML development at 2 years was similar in the NTZ-ctr group and replication cohort. Serum NFL levels also distinguished PML from MS relapses and were 8-fold higher during PML compared with relapses.ConclusionsThese results support the use of serum NFL levels in clinical practice to identify patients with relapsing-remitting MS at higher PML risk and to differentiate PML from clinical relapses in NTZ-treated patients.Classification of EvidenceThis study provides Class I evidence that serum NFL levels can identify NTZ-treated patients with MS who will develop PML with a sensitivity of 67% and specificity of 80%.
- Published
- 2021