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Objective  To investigate whether blood–brain barrier (BBB) permeability, as measured by dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI), can provide early detection of suboptimal treatment response in relapsing–remitting multiple sclerosis (RRMS).    Methods  Thirty‐five RRMS patients starting on fingolimod or natalizumab, drugs with a common effect of decreasing lymphocyte influx into the central nervous system, were scanned with DCE‐MRI at 3T prior to treatment and at 3 and 6 months posttreatment. We calculated the influx constant K i , a measure of BBB permeability, using the Patlak model. Suboptimal treatment response was defined as loss of no evidence of disease activity (NEDA) status after 2 years of treatment.    Results  Subjects with loss of NEDA status at 2 years had a 51% higher mean K i  in normal‐appearing white matter (NAWM) measured after 6 months of treatment, compared to subjects with maintained NEDA status (mean difference = 0.06ml/100g/min, 95% confidence interval [CI] = 0.02–0.09,  p  = 0.002). K i  in NAWM at 6 months was a good predictor of loss of NEDA status at 2 years (area under the curve = 0.84, 95% CI = 0.70–0.99,  p  = 0.003), and a value above 0.136ml/100/g/min yielded an odds ratio of 12.4 for suboptimal treatment response at 2 years, with a sensitivity of 73% and a specificity of 82%.    Interpretation  Our results suggest that BBB permeability as measured by DCE‐MRI reliably predicts suboptimal treatment response and is a surrogate marker of the state of health of the BBB. We find a predictive threshold for disease activity, which is remarkably identical in clinically isolated syndrome as previously reported and established RRMS as investigated here. Ann Neurol 2018;83:902–914

annals of neurology

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