Adding brain volume measures into response criteria in multiple sclerosis: the Río-4 score

Purpose: Brain volume changes (BVC) on therapy in MS are being considered as predictor for treatment response at an individual level. We ought to assess whether adding BVC as a factor to monitor interferon-beta response improves the predictive ability of the (no) evidence of disease activity (EDA-3) and Río score (RS-3) criteria for confirmed disability progression in a historical cohort. Methods: One hundred one patients from an observational cohort treated with interferon-beta were assessed for different cutoff points of BVC (ranged 0.2–1.2%), presence of active lesions (≥ 1 for EDA/≥ 3 for RS), relapses, and 6-month confirmed disability progression (CDP), measured by the Expanded Disability Status Scale, after 1 year. Sensitivity, specificity, and positive and negative predictive values for predicting confirmed disability progression at 4 years in original EDA (EDA-3) and RS (RS-3) as well as EDA and RS including BVC (EDA-4 and RS-4) were compared. Results: Adding BVC to EDA slightly increased sensitivity, but not specificity or predictive values, nor the OR for predicting CDP; only EDA-3 showed a trend for predicting CDP (OR 3.701, p = 0.050). Adding BVC to RS-3 (defined as ≥ 2 criteria) helped to improve sensitivity and negative predictive value, and increased OR for predicting CDP using a cutoff of ≤ − 0.86% (RS-3 OR 23.528, p < 0.001; RS-4 for all cutoffs ranged from 15.06 to 32, p < 0.001). RS-4 showed areas under the curve larger than RS-3 for prediction of disability at 4 years. Conclusion: Addition of BVC to RS improves its prediction of response to interferon-beta.