Soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and Natalizumab Serum Concentration as Potential Biomarkers for Pharmacodynamics and Treatment Response of Patients with Multiple Sclerosis Receiving Natalizumab.
CNS Drugs
; 36(10): 1121-1131, 2022 10.
Article
in En
| MEDLINE
| ID: mdl-36173556
ABSTRACT
BACKGROUND:
Natalizumab (NTZ) is an established treatment for highly active, relapsing-remitting multiple sclerosis. In the context of rare progressive multifocal leukoencephalopathy and extended interval dosing as a treatment option, biomarkers for treatment monitoring are required. Natalizumab serum concentration (NTZ SC) and soluble vascular cell adhesion molecule 1 (sVCAM-1) concentration were shown to change on treatment with NTZ. We aimed to investigate whether NTZ SC and sVCAM-1 could be suitable pharmacodynamic markers and whether they could predict disease activity on NTZ, improving the concept of personalized multiple sclerosis treatment.METHODS:
In a retrospective study at the Medical University of Innsbruck, Austria, we identified patients treated with NTZ and chose samples longitudinally collected during routine follow-ups for the measurement of NTZ SC and sVCAM-1 by an enzyme-linked immunosorbent assay. We correlated these with clinical and demographic variables and clinical outcomes. Furthermore, we analyzed the stability of NTZ SC and sVCAM-1 during treatment.RESULTS:
One hundred and thirty-seven patients were included. We found a strong negative correlation between NTZ SC and sVCAM-1. Both showed significant associations with body mass index, infusion interval, sample age, and anti-drug-antibodies. Natalizumab serum concentration was reduced in extended interval dosing, but not sVCAM-1. Only sVCAM-1 showed a weak association with relapses during treatment, while there was no association with disease progression. Both NTZ SC and sVCAM-1 showed a wide inter-individual distribution while levels in single patients were stable on treatment.CONCLUSIONS:
Soluble vascular cell adhesion molecule 1 is a suitable pharmacodynamic marker during treatment with NTZ, which is significantly reduced already after the first dose, remains stable in individual patients even on extended interval dosing, and strongly correlates with NTZ SC. Because of the high inter-individual range, absolute levels of sVCAM-1 and NTZ SC are difficult to introduce as treatment monitoring biomarkers in order to predict disease activity in single patients.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vascular Cell Adhesion Molecule-1
/
Multiple Sclerosis, Relapsing-Remitting
/
Natalizumab
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
CNS Drugs
Journal subject:
FARMACOLOGIA
/
NEUROLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2022
Document type:
Article
Affiliation country: