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 - Copyright © 2022. Published by Elsevier B.V.
PY - 2022/7
Y1 - 2022/7
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/therapeutic use
KW - Blood-Brain Barrier
KW - Humans
KW - Magnetic Resonance Imaging
KW - Multiple Sclerosis, Relapsing-Remitting/chemically induced
KW - Multiple Sclerosis/chemically induced
KW - Permeability
UR - http://www.scopus.com/inward/record.url?scp=85131427582&partnerID=8YFLogxK
U2 - 10.1016/j.msard.2022.103891
DO - 10.1016/j.msard.2022.103891
M3 - Journal article
C2 - 35661562
VL - 63
JO - Multiple Sclerosis and Related Disorders
JF - Multiple Sclerosis and Related Disorders
SN - 2211-0348
M1 - 103891
ER -