Permeability of the blood–brain barrier predicts no evidence of disease activity at 2 years after natalizumab or fingolimod treatment in relapsing–remitting multiple sclerosis
Autor: | Stig P. Cramer, Henrik Larsson, Jette L. Frederiksen, Helle J. Simonsen, Ian Galea, Aravinthan Varatharaj |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Gastroenterology Permeability 03 medical and health sciences 0302 clinical medicine Natalizumab Multiple Sclerosis Relapsing-Remitting Internal medicine medicine Humans Research Articles Clinically isolated syndrome medicine.diagnostic_test Surrogate endpoint business.industry Fingolimod Hydrochloride Multiple sclerosis Area under the curve Magnetic resonance imaging Middle Aged medicine.disease Fingolimod Magnetic Resonance Imaging White Matter Confidence interval 030104 developmental biology Neurology Blood-Brain Barrier Female Neurology (clinical) business 030217 neurology & neurosurgery medicine.drug Research Article |
Zdroj: | Annals of Neurology Cramer, S P, Simonsen, H J, Varatharaj, A, Galea, I, Frederiksen, J L & Larsson, H B W 2018, ' Permeability of the blood–brain barrier predicts no evidence of disease activity at 2 years after natalizumab or fingolimod treatment in relapsing–remitting multiple sclerosis ', Annals of Neurology, vol. 83, no. 5, pp. 902-914 . https://doi.org/10.1002/ana.25219 |
ISSN: | 1531-8249 0364-5134 |
Popis: | Objective: To investigate whether blood–brain barrier (BBB) permeability, as measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), can provide early detection of suboptimal treatment response in relapsing–remitting multiple sclerosis (RRMS). Methods: Thirty-five RRMS patients starting on fingolimod or natalizumab, drugs with a common effect of decreasing lymphocyte influx into the central nervous system, were scanned with DCE-MRI at 3T prior to treatment and at 3 and 6 months posttreatment. We calculated the influx constant Ki, a measure of BBB permeability, using the Patlak model. Suboptimal treatment response was defined as loss of no evidence of disease activity (NEDA) status after 2 years of treatment. Results: Subjects with loss of NEDA status at 2 years had a 51% higher mean Ki in normal-appearing white matter (NAWM) measured after 6 months of treatment, compared to subjects with maintained NEDA status (mean difference = 0.06ml/100g/min, 95% confidence interval [CI] = 0.02–0.09, p = 0.002). Ki in NAWM at 6 months was a good predictor of loss of NEDA status at 2 years (area under the curve = 0.84, 95% CI = 0.70–0.99, p = 0.003), and a value above 0.136ml/100/g/min yielded an odds ratio of 12.4 for suboptimal treatment response at 2 years, with a sensitivity of 73% and a specificity of 82%. Interpretation: Our results suggest that BBB permeability as measured by DCE-MRI reliably predicts suboptimal treatment response and is a surrogate marker of the state of health of the BBB. We find a predictive threshold for disease activity, which is remarkably identical in clinically isolated syndrome as previously reported and established RRMS as investigated here. Ann Neurol 2018;83:902–914. |
Databáze: | OpenAIRE |
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