Blood-brain barrier permeability changes in the first year after alemtuzumab treatment predict 2-year outcomes in relapsing-remitting multiple sclerosis

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.

Keywords: Alemtuzumab; Biomarker; MRI; Neuroimaging; Relapsing-remitting multiple sclerosis.