Evidence of disease control: a realistic concept beyond NEDA in the treatment of multiple sclerosis

Abstract

Although no evidence of disease activity (NEDA) permits evaluation of response to treatment in the systematic follow-up of patients with multiple sclerosis (MS), its ability to accomplish detection of surreptitious activity of disease is limited, thus being unable to prevent patients from falling into a non-reversible progressive phase of disease. A protocol of evaluation based on the use of validated biomarkers that is conducted at an early stage of disease would permit the capture of abnormal neuroimmunological phenomena and lead towards intervention with modifying therapy before tissue damage has been reached.

Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis

“…The search for valid biomarkers for patients with MS has been unsatisfying throughout many years. Particularly at the beginning of the disease, prospective biomarkers could facilitate therapy decisions, permit the detection of neuroimmunological activity before structural damage becomes prominent 10 and therefore lead to better patient outcome and decreased incidence of transition to progressive disease course in the long term. 11 So far, female sex, pure sensory onset, lower age at onset and other prognostic factors are associated with a benign course in early RRMS patients.…”

Reviewing the Significance of Blood–Brain Barrier Disruption in Multiple Sclerosis Pathology and Treatment

“…The concept of 'no evidence of disease activity' (NEDA) evolved over the last decade, from the criterion of no disease activity (stable neurological examination, no relapses, no new or enhancing MRI lesions) as the gold standard for therapy to more complex criteria to affirm that a patient has NEDA. The most recent NEDA 8 adds other signs of disease progression, such as cognitive decline, CSF light chain neurofilament, loss of brain volumes, patient-related outcome, and oligoclonal bands, to the previous criteria [62]. Elliot et al considered progressive clinical evolution in patients with no MRI Gd+ activity to be secondary to smoldering demyelination or the so-called 'silent progression' (after Cree et al), which is correlated with brain atrophy independent of relapses [63,64].…”