Five- and seven-year prognostic value of new effectiveness measures (NEDA, MEDA and six-month delayed NEDA) in relapsing-remitting multiple sclerosis

Abstract

The concept of ‘no evidence of disease activity’ (NEDA) has been proposed as a surrogate marker for treatment response in relapsing-remittent multiple sclerosis (MS). However, there is no agreement regarding its prognostic value, nor about the starting time for evaluation of drug effectiveness. Aim of this study was to investigate if the status preservation of two-year NEDA, ‘minimal evidence of disease activity’ (MEDA) and six-month delayed NEDA (6md-NEDA, with a “rebaseline” six months after the treatment start) predicts the achievement of long-term disability outcomes (EDSS score ≥ 4.0 or 6.0, 3-month confirmed disability progression (CDP) or conversion to secondary progressive MS) after five and seven years of disease. A total of 271 treatment courses (TCs) were analyzed in this retrospective study, involving all TCs started with any disease-modifying treatments (DMT). Overall, 72 (27%), 77 (28%) and 92 (34%) TCs maintained NEDA, MEDA and 6md-NEDA status after a two-year treatment. NEDA, MEDA and 6md-NEDA TCs had a lower risk of attaining all disability outcomes, compared to ‘evidence of disease activity’ (EDA) TCs. NEDA status determined a lower risk of CDP after five (OR 0.18, 95% CI 0.07–0.45, p < .0001) and seven years of disease (OR 0.15, 95% CI 0.05–0.44, p < .0001), with high positive (90%) and low negative (42%) predictive value, good specificity and low sensitivity. NEDA TCs had a lower risk of CDP compared to MEDA TCs after seven years (OR 0.30, 95% CI 0.10–0.91, p = .04). 6md-NEDA had a small impact on the improvement of NEDA prognostic value.