The evolution of "No Evidence of Disease Activity" in multiple sclerosis

The availability of effective therapies for patients with relapsing-remitting multiple sclerosis (RRMS) has prompted a re-evaluation of the most appropriate way to measure treatment response, both in clinical trials and clinical practice. Traditional parameters of treatment efficacy such as annualized relapse rate, magnetic resonance imaging (MRI) activity, and disability progression have an important place, but their relative merit is uncertain, and the role of other factors such as brain atrophy is still under study. More recently, composite measures such as "no evidence of disease activity" (NEDA) have emerged as new potential treatment targets, but NEDA itself has variable definitions, is not well validated, and may be hard to implement as a treatment goal in a clinical setting. We describe the development of NEDA as an outcome measure in MS, discuss definitions including NEDA-3 and NEDA-4, and review the strengths and limitations of NEDA, indicating where further research is needed.