Pharmacodynamics of natalizumab extended interval dosing in MS.
Journal
Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
23
09
2019
accepted:
23
12
2019
entrez:
6
2
2020
pubmed:
6
2
2020
medline:
7
5
2021
Statut:
epublish
Résumé
To determine if the concentration and saturation of natalizumab (NTZ) administration at extended interval dosing (EID; every 5-8 weeks) over 18 months is able to be maintained in the range considered adequate to sustain the clinical efficacy of NTZ. In a cross-sectional assessment of patients with multiple sclerosis (MS) who received standard interval dosing (every 4 weeks) or EID, serum NTZ concentrations were measured using ELISA, and α Trough serum concentration was above the "therapeutic" concentration of 2.0 μg/mL in 72% of EID patients. Trough saturation was above the "therapeutic" 50% threshold in 79% of EID-treated patients. Our model predicted that at least 9 NTZ infusions/year are required to maintain adequate trough saturation and concentration levels. Higher body mass index (BMI) was a predictor of suboptimal trough saturation on EID NTZ. Trough α4-integrin receptor saturation >50% correlated with high clinical efficacy of NTZ in previous studies. A continual treatment with EID maintains receptor saturation and concentration that are in the "therapeutic range" for most patients. This finding provides biological plausibility for the clinical efficacy of NTZ EID. Patients with higher BMI may require closer clinical and MRI follow-up.
Identifiants
pubmed: 32019876
pii: 7/2/e672
doi: 10.1212/NXI.0000000000000672
pmc: PMC7057061
pii:
doi:
Substances chimiques
Immunologic Factors
0
Natalizumab
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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