Serum Neurofilament Levels and PML Risk in Patients With Multiple Sclerosis Treated With Natalizumab

Nicolás Fissolo (1, 2, 3) , Beatrice Pignolet (4, 5) , Jordi Rio (6, 2) , Patrick Vermersch (7) , Aurélie Ruet (8, 9) , Jerome Desèze (10) , Pierre Labauge (11) , Sandra Vukusic (12) , Caroline Papeix (13) , Laurent Martinez-Almoyna (14) , Ayman Tourbah (15, 16) , Pierre Clavelou (17) , Thibault Moreau (18) , Jean Pelletier (19, 20) , Christine Lebrun-Frenay (21, 22) , Bertrand Bourre (23) , Gilles Defer (24) , Xavier Montalban (6, 2) , David Brassat (4, 5) , Manuel Comabella (1, 2, 3)

1 UAB - Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona
2 CemCat - Centre d'Esclerosi Múltiple de Catalunya
3 VHIR - Vall d’Hebron Research Institute
4 CPTP - Centre de Physiopathologie Toulouse Purpan
5 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
6 Vall d'Hebron University Hospital [Barcelona]
7 LilNCog - Lille Neurosciences & Cognition - U 1172
8 U1215 Inserm - UB - Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale
9 CHU Bordeaux
10 Service de Neurologie [Strasbourg]
11 Département de neurologie [Montpellier]
12 Service de Neurologie [Lyon]
13 CHU Pitié-Salpêtrière [AP-HP]
14 Service de Neurologie [Aix-en-Provence]
15 LPN - Laboratoire de Psychopathologie et Neuropsychologie
16 Service de neurologie [Reims]
17 Service de Neurologie [CHU Clermont-Ferrand]
18 Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon)
19 TIMONE - Hôpital de la Timone [CHU - APHM]
20 CRMBM - Centre de résonance magnétique biologique et médicale
21 Service de Neurologie [CHU Nice]
22 UniCA - Université Côte d'Azur
23 Service de neurologie [Rouen]
24 Service de Neurologie [CHU Caen]

Objectives: The 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. Methods: NFL 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. Results: Serum 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. Conclusions: These 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 evidence: This 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%.

Domains: Human health and pathology; Neurons and Cognition [q-bio.NC]; Immunology

Nicolás Fissolo, Beatrice Pignolet, Jordi Rio, Patrick Vermersch, Aurélie Ruet, et al.. Serum Neurofilament Levels and PML Risk in Patients With Multiple Sclerosis Treated With Natalizumab. Neurology Neuroimmunology & Neuroinflammation, 2021, 8 (4), pp.e1003. ⟨10.1212/NXI.0000000000001003⟩. ⟨hal-03451407⟩