Natalizumab in Multiple Sclerosis Treatment: From Biological Effects to Immune Monitoring.
Antibodies, Monoclonal
/ pharmacology
Disease Susceptibility
Drug Monitoring
Humans
Integrin alpha4
/ antagonists & inhibitors
Leukoencephalopathy, Progressive Multifocal
/ complications
Molecular Targeted Therapy
Multiple Sclerosis
/ diagnosis
Natalizumab
/ pharmacology
T-Lymphocyte Subsets
/ drug effects
Treatment Outcome
Integrin
Mab therapy monitoring
PML
biotherapy
drug modifying therapy
multiple sclerosis
natalizumab
neutralizing antibodies
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
07
04
2020
accepted:
04
09
2020
entrez:
19
10
2020
pubmed:
20
10
2020
medline:
15
5
2021
Statut:
epublish
Résumé
Multiple sclerosis is a chronic demyelinating disease of the central nervous system (CNS) with an autoimmune component. Among the recent disease-modifying treatments available, Natalizumab, a monoclonal antibody directed against the alpha chain of the VLA-4 integrin (CD49d), is a potent inhibitor of cell migration toward the tissues including CNS. It potently reduces relapses and active brain lesions in the relapsing remitting form of the disease. However, it has also been associated with a severe infectious complication, the progressive multifocal leukoencephalitis (PML). Using the standard protocol with an injection every 4 weeks it has been shown by a close monitoring of the drug that trough levels soon reach a plateau with an almost saturation of the target cell receptor as well as a down modulation of this receptor. In this review, mechanisms of action involved in therapeutic efficacy as well as in PML risk will be discussed. Furthermore the interest of a biological monitoring that may be helpful to rapidly adapt treatment is presented. Indeed, development of anti-NAT antibodies, although sometimes unapparent, can be detected indirectly by normalization of CD49d expression on circulating mononuclear cells and might require to switch to another drug. On the other hand a stable modulation of CD49d expression might be useful to follow the circulating NAT levels and apply an extended interval dose scheme that could contribute to limiting the risk of PML.
Identifiants
pubmed: 33072089
doi: 10.3389/fimmu.2020.549842
pmc: PMC7541830
doi:
Substances chimiques
Antibodies, Monoclonal
0
Natalizumab
0
Integrin alpha4
143198-26-9
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
549842Informations de copyright
Copyright © 2020 Khoy, Mariotte, Defer, Petit, Toutirais and Le Mauff.
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