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 -