NEDA (no evidence of disease activity)

No evidence of disease activity (NEDA), also referred to as freedom from disease activity, is a new goal that is emerging in multiple sclerosis treatment. The aim is to treat people with relapsing remitting MS (RRMS) with disease modifying drugs (DMDs) to reach a point where they are having:

  • no relapses
  • no increase in disability (as measured by EDSS)
  • no new or active (enhancing) lesions on their MRI scans.

This is sometimes referred to as NEDA-3 for the three components of disease activity involved. Some studies use NEDA-4 and include measures of brain shrinkage (atrophy) as a fourth component.

In the past, treatment of people with RRMS has been focused solely on reducing the number of relapses. The person with MS would be started on a moderately effective DMD, escalating to alternative drugs only after the first one was shown to be ineffective by allowing breakthrough disease activity in the form of relapses.

However, relapses may not be a sufficient indicator of MS activity. The inflammation caused by MS does not always result in a relapse or any visible symptoms. This silent MS activity may mean that there are changes caused by your MS that can only be seen on a brain scan. The aim of NEDA is to reach a point where you are free of the silent disease activity as well as visible changes in your MS. 

This concept of being ‘disease free’ is based on a treatment approach that has been found to be successful in the treatment of people with cancer and rheumatoid arthritis. The idea is to start disease modifying drug (DMD) treatment as soon as possible after diagnosis to prevent a build-up of symptoms and nerve damage. If you do not respond to treatment and MS activity is detected then your treatment would be reviewed to consider switching to another drug which may be more effective.

The concept of NEDA is still evolving, but long term follow ups show that being defined as NEDA is strongly related to a better health and disability status 16 and 21 years later.

Whilst a growing number of neurologists with a specialist interest in MS are encouraging this early, proactive approach to managing RRMS, not all neurologists will take the same view and some national guidance does not yet reflect this strategy. If you have RRMS, then do raise the issue of early treatment and how it might apply to you with your MS team.

NEPAD (no evidence of progression or active disease)

For those with progressive MS, the goal of NEPAD, or 'no evidence of progression or active disease' is considered by some to be more appropriate than NEDA. In relapsing remitting MS, relapses are clinically important, and their frequency will guide treatment decisions. In progressive forms of MS, increasing disability is the chief concern, and so more emphasis is placed on slowing or preventing progression.

The concept of NEPAD was introduced as part of the work done to evaluate the efficacy of Ocrevus (ocrelizumab). In addition to the EDSS measurement of disability, researchers also looked at walking tests and the 9-hole peg test as an indicator of arm function, to measure whether the drug was slowing the progressive accumulation of disability.

Find out more

Giovannoni G et al.
Is it time to target no evident disease activity (NEDA) in multiple sclerosis?
Multiple Sclerosis and Related Disorders 2015;4(4):329-333.
Full article (link is external)
Rotstein DL et al.
Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort.
JAMA Neurology 2015;72(2):152-158.
Summary (link is external)
Rotstein, D et al.
Association of NEDA-4 With No Long-term Disability Progression in Multiple Sclerosis and Comparison With NEDA-3: A Systematic Review and Meta-analysis
Neurol Neuroimmunol Neuroinflamm . 2022 Oct 12;9(6):e200032.
Summary (link is external)