TY - JOUR
T1 - Serum Neurofilament Levels and PML Risk in Patients With Multiple Sclerosis Treated With Natalizumab
AU - Fissolo, Nicolás
AU - Pignolet, Beatrice
AU - Rio, Jordi
AU - Vermersch, Patrick
AU - Ruet, Aurélie
AU - deSèze, Jerome
AU - Labauge, Pierre
AU - Vukusic, Sandra
AU - Papeix, Caroline
AU - Martinez-Almoyna, Laurent
AU - Tourbah, Ayman
AU - Clavelou, Pierre
AU - Moreau, Thibault
AU - Pelletier, Jean
AU - Lebrun-Frenay, Christine
AU - Bourre, Bertrand
AU - Defer, Gilles
AU - Montalban, Xavier
AU - Brassat, David
AU - Comabella, Manuel
N1 - Publisher Copyright:
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - 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%.
AB - 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%.
UR - https://www.scopus.com/pages/publications/85105905534
U2 - 10.1212/NXI.0000000000001003
DO - 10.1212/NXI.0000000000001003
M3 - Article
C2 - 33903203
AN - SCOPUS:85105905534
SN - 2332-7812
VL - 8
JO - Neurology: Neuroimmunology and NeuroInflammation
JF - Neurology: Neuroimmunology and NeuroInflammation
IS - 4
ER -