"No evidence of disease activity": Is it an aspirational therapeutic goal in multiple sclerosis?

'No evidence of disease activity' (NEDA) that has been identified as a potential outcome measure for the evaluation of DMTs effects. The concept has been adopted from other diseases such as cancer where treatment is intended to free the patient from the disease. Disease-free status has been substituted by NEDA in MS, since we are limited when it comes to fully evaluating the underlying disease. In general, NEDA, otherwise termed as NEDA-3, is defined by the lack of disease activity based on the absence of clinical relapses, disability progression with the expanded disability status score (EDSS), and radiological activity. Recently, brain atrophy, a highly predictive marker of disability progression, has been added as a fourth component (NEDA-4). The use of this composite allowed a more comprehensive assessment of the disease activity. Indeed, it has an important role in clinical trials as a secondary outcome in addition to primary endpoints. However, the evidence is insufficient regarding the ability of NEDA to predict future disability and treatment response. Moreover, combining different composites does not eliminate the limitation of each, therefore the use of NEDA in clinical routine is still not implemented. The aim of this review is first to report from the literature the available definitions of NEDA and its different variants, and second, evaluate the importance of its use as a surrogate marker to assess the efficacy of different DMTs.