Blood-Brain Barrier Permeability Predicts Treatment Response in MS

Disease-modifying therapies natalizumab and fingolimod, used to treat patients with relapsing-remitting multiple sclerosis, can reduce the occurrence and severity of relapses by mediating lymphocyte passage across the blood-brain barrier. Detecting the health of normal-appearing white matter is an indicator for blood-brain barrier permeability and can be used to predict treatment efficacy, according to a study published in the Annals of Neurology.

The prospective study included 35 participants with relapsing-remitting multiple sclerosis starting natalizumab or fingolimod treatment, who were evaluated using dynamic-contrast enhanced MRI (DCE-MRI) prior to treatment, and again at 3 months and 6 months following treatment. Blood-brain barrier permeability was measured by calculating the influx constant Ki in normal-appearing white matter (NAWM); there was no difference in mean Ki in the pre-treatment evaluation of subjects.

The goal of treatment proposed a zero-tolerance threshold; the treatment status was evaluated against the concept of no-evidence-of-disease activity (NEDA) and sub-optimal treatment was indicated by a loss of NEDA status. Study results reported that patients with a loss of NEDA status after 2 years of treatment demonstrated a 51% higher mean Ki in NAWM measured 6 months after initiating treatment. This suggests that a high Ki response (as measured by DCE-MRI) was a significant predictor of a sub-optimal treatment effect.

Study findings that used the physical integrity of the blood-brain barrier to predict an individual patient’s treatment response within the first 2 years show that blood-brain barrier health may even provide long-term prognostic information.

Reference

Cramer SP, Simonsen HJ, Varatharaj A, Galea I, Frederiksen JL, Larsson HBW. Permeability of the blood-brain barrier predicts no evidence of disease activity at 2 years after natalizumab or fingolimod treatment in relapsing-remitting multiple sclerosis [published online March 31, 2018]. Ann Neurol. doi: 10.1002/ana.25219