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sNFL applicability as additional monitoring tool in natalizumab extended interval dosing regimen for RRMS patients

  • Paola Valentino
    Correspondence
    Corresponding author at: Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, Orbassano 10043, Italy.
    Affiliations
    Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, Orbassano 10043, Italy

    CRESM Biobank, University Hospital San Luigi Gonzaga, Regione Gonzole 10, Orbassano 10043, Italy
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  • Simona Malucchi
    Affiliations
    Department of Neurology and CRESM, University Hospital San Luigi Gonzaga, Regione Gonzole 10, Orbassano 10043, Italy
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  • Serena Martire
    Affiliations
    Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, Orbassano 10043, Italy

    Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Via Cherasco 15, Turin 10100, Italy
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  • Cecilia Irene Bava
    Affiliations
    Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, Orbassano 10043, Italy
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  • Marco Alfonso Capobianco
    Affiliations
    CRESM Biobank, University Hospital San Luigi Gonzaga, Regione Gonzole 10, Orbassano 10043, Italy

    Department of Neurology, S. Croce e Carle Hospital, Via Michele Coppino, 26, Cuneo 12100, Italy
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  • Antonio Bertolotto
    Affiliations
    Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, Orbassano 10043, Italy

    Department of Neurology, Koelliker Hospital, C.so Galileo Ferraris, 247/255, Turin 10134, Italy
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Published:September 13, 2022DOI:https://doi.org/10.1016/j.msard.2022.104176

      Abstract

      Introduction

      Extended interval dosing (EID) of Natalizumab (NAT) has been proposed to reduce progressive multifocal leukoencephalopathy (PML) risk associated with standard interval dosing (SID) in people with multiple sclerosis (MS). Previous studies have suggested that NAT effectiveness is maintained in the great majority of patients who switch from SID to EID; monitoring of disease activity is currently based exclusively on clinical and MRI parameters. Frequent MRI are expensive and not always applicable, underlining the need for biological markers able to detect central nervous system lesions. Serum Neurofilament-light chain (sNFL) currently represents the most promising biomarker of disease activity, prognosis and treatment response in MS, and their clinical suitability is increasingly evident. The objective of the present study is to assess the applicability of sNFL as additional/alternative measure of treatment efficacy during EID regimen.

      Methods

      We measured sNFL by Simoa technology in longitudinal samples from 63 Relapsing Remitting (RR) MS patients switched from SID to EID. Inclusion criteria: diagnosis of RRMS, age 18-60 years; NAT SID for at least 12 months; NEDA-3 (no evidence of disease activity) for at least 12 months; availability of at least 2 serum samples collected 6 months apart. Patients’ follow-up time during EID was at least 12 months and 2 blood samples were collected after at least 6 and 12 months. Clinical examination was performed before each infusion, while MRI 6 and 12 months after NAT initiation and according to PML risk during the whole study.

      Results

      No patients showed clinical or MRI activity during the whole follow-up. sNFL levels measured during SID and EID were comparable, without significant difference between groups. The effect of EID on NFL levels did not show significant effects (LMM, p> 0.05) and sNFL levels did not vary with time during SID or EID protocols (LMM, p> 0.05). Intra-individual sNFL levels demonstrated overall stability during SID and EID (median CV=11% between SID and EID samples). According to our previously published reference values, sNFL levels were in the normal range in all samples, both during SID and EID.

      Conclusions

      Our results suggest that sNFL quantification can be used as an alternative/additional approach to MRI in managing individual patients. The present work provides a new clinical application of sNFL to monitor NAT efficacy.

      Keywords

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