Blood-brain barrier permeability changes in the first year after alemtuzumab treatment predict 2-year outcomes in relapsing-remitting multiple sclerosis
Maria Højberg Knudsen, Ulrich Lindberg, Jette Lautrup Frederiksen, Mark Bitsch Vestergaard, Helle Juhl Simonsen, Aravinthan Varatharaj, Ian Galea, Morten Blinkenberg, Finn Sellebjerg, Henrik Larsson, Stig P. Cramer
Abstract
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 (K i ) 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 K i 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 K i 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.