Blood-brain barrier permeability changes in the first year after alemtuzumab treatment predict 2-year outcomes in relapsing-remitting multiple sclerosis
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Blood-brain barrier permeability changes in the first year after alemtuzumab treatment predict 2-year outcomes in relapsing-remitting multiple sclerosis. / Knudsen, Maria Højberg; Lindberg, Ulrich; Frederiksen, Jette Lautrup; Vestergaard, Mark Bitsch; Simonsen, Helle Juhl; Varatharaj, Aravinthan; Galea, Ian; Blinkenberg, Morten; Sellebjerg, Finn; Larsson, Henrik Bo Wiberg; Cramer, Stig Præstekjær.
In: Multiple Sclerosis and Related Disorders, Vol. 63, 103891, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Blood-brain barrier permeability changes in the first year after alemtuzumab treatment predict 2-year outcomes in relapsing-remitting multiple sclerosis
AU - Knudsen, Maria Højberg
AU - Lindberg, Ulrich
AU - Frederiksen, Jette Lautrup
AU - Vestergaard, Mark Bitsch
AU - Simonsen, Helle Juhl
AU - Varatharaj, Aravinthan
AU - Galea, Ian
AU - Blinkenberg, Morten
AU - Sellebjerg, Finn
AU - Larsson, Henrik Bo Wiberg
AU - Cramer, Stig Præstekjær
N1 - Publisher Copyright: © 2022
PY - 2022
Y1 - 2022
N2 - Background: In relapsing-remitting multiple sclerosis (RRMS), early disease control reduces the risk of permanent disability. The blood–brain barrier (BBB) is compromised in MS, and its permeability is a potential biomarker. Objective: To investigate BBB permeability measured by MRI as a marker of alemtuzumab efficacy. Methods: Patients with RRMS initiating alemtuzumab treatment were recruited prospectively. BBB permeability was assessed as the Patlak-derived influx constant (Ki) by dynamic contrast-enhanced MRI before and 6, 12, and 18 months after the first course of alemtuzumab. No Evidence of Disease Activity-3 (NEDA-3) status was ascertained two years after treatment initiation. Results: Patients who maintained NEDA-3 status at two years (n = 7) had a larger decrease in Ki between baseline and six months (-0.029 ml/100 g/min [CI -0.005 − -0.053]) and between baseline and 12 months in normal appearing white matter (0.043 [CI 0.022 – -0.065]), than those who experienced disease activity (n = 8). ROC curve analysis of the Ki change between baseline and 12 months in NAWM predicted a loss of NEDA status at 2 years with 86% sensitivity and 86% specificity (AUC 0.98, p = 0.002). Conclusion: BBB permeability predicted alemtuzumab efficacy at two years, indicating that BBB permeability is a biomarker of treatment response in RRMS.
AB - Background: In relapsing-remitting multiple sclerosis (RRMS), early disease control reduces the risk of permanent disability. The blood–brain barrier (BBB) is compromised in MS, and its permeability is a potential biomarker. Objective: To investigate BBB permeability measured by MRI as a marker of alemtuzumab efficacy. Methods: Patients with RRMS initiating alemtuzumab treatment were recruited prospectively. BBB permeability was assessed as the Patlak-derived influx constant (Ki) by dynamic contrast-enhanced MRI before and 6, 12, and 18 months after the first course of alemtuzumab. No Evidence of Disease Activity-3 (NEDA-3) status was ascertained two years after treatment initiation. Results: Patients who maintained NEDA-3 status at two years (n = 7) had a larger decrease in Ki between baseline and six months (-0.029 ml/100 g/min [CI -0.005 − -0.053]) and between baseline and 12 months in normal appearing white matter (0.043 [CI 0.022 – -0.065]), than those who experienced disease activity (n = 8). ROC curve analysis of the Ki change between baseline and 12 months in NAWM predicted a loss of NEDA status at 2 years with 86% sensitivity and 86% specificity (AUC 0.98, p = 0.002). Conclusion: BBB permeability predicted alemtuzumab efficacy at two years, indicating that BBB permeability is a biomarker of treatment response in RRMS.
KW - Alemtuzumab
KW - Biomarker
KW - MRI
KW - Neuroimaging
KW - Relapsing-remitting multiple sclerosis
U2 - 10.1016/j.msard.2022.103891
DO - 10.1016/j.msard.2022.103891
M3 - Journal article
C2 - 35661562
AN - SCOPUS:85131427582
VL - 63
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
SN - 2211-0348
M1 - 103891
ER -
ID: 310434952