Achieving no evident disease activity (NEDA) may become the "new normal" state of disease control for patients with multiple sclerosis (MS). This aspirational goal has been compared with the use of biological disease-modifying therapies (DMTs) to achieve disease remission in patients with rheumatoid arthritis.
In a recent article, published in the Multiple Sclerosis Journal,1 Gavin Giovannoni and colleagues reviewed the role of combined assessments of NEDA that factor in brain volume changes or neuropsychological outcomes. Such a combined assessment would need to be validated in prospective studies at the individual patient level as being indicative of long-term disease remission.
In the past, NEDA took into account brain magnetic resonance imaging (MRI), the occurrence of relapse, as well as disease worsening. It has not historically included a measure of neurodegenerative damage, placing emphasis instead on inflammatory activity. Thus, three-domain NEDA (NEDA-3) assessment has been questioned as providing an incomplete picture of disease activity in MS. To add to the controversy, there is no clear agreement regarding the definition of the different disease components that constitute NEDA-3. In addition, NEDA-3 appears difficult to sustain in the long-term, even with treatment.2,3 In support of this, cognitive deterioration has been observed in patients who have achieved NEDA-3.4
In the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women’s Hospital (CLIMB study), 99 of 215 patients (46.0%) had NEDA for clinical and MRI measures at 1 year, but only 17 of 216 (7.9%) maintained NEDA status after 7 years.2 At 2 years, NEDA had a positive predictive value of 78.3% for no progression at 7 years (as measured by an Expanded Disability Status Scale score change ≤0.5). It is not yet known how the relationship between observation period and prognostic power varies among different DMTs and such an understanding will be critical if NEDA is to be used to inform treatment decisions in clinical practice.
In 2015, Gavin Giovannoni et al.5 predicted that the definition of NEDA will evolve as technological innovations are adopted into clinical practice. It is therefore possible that neuropsychological outcomes as well as brain volume loss could be included in future NEDA definitions. However, whether this would make assessment of NEDA too complicated, time-consuming and unrealistic for clinical practice is unclear.
1. Giovannoni G, Tomic D, Bright JR, et al., "No evident disease activity": the use of combined assessments in the management of patients with multiple sclerosis, Mult Scler, 2017;23:1179–87.
2. Rotstein DL, Healy BC, Malik MT, et al., Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort, JAMA Neurol, 2015;72:152–8.
3. Uher T, Havrdova E, Sobisek L, et al., Is no evidence of disease activity an achievable goal in MS patients on intramuscular interferon beta-1a treatment over long-term follow-up?, Mult Scler, 2017;23:242–52.
4. Damasceno A, Damasceno BP, Cendes F, No evidence of disease activity in multiple sclerosis: implications on cognition and brain atrophy, Mult Scler, 2016;22:64–72.
5. Giovannoni G, Turner B, Gnanapavan S, et al., Is it time to target no evident disease activity (NEDA) in multiple sclerosis?, Mult Scler Relat Disord, 2015;4:329–33.