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JAMA Neurol. 2015 Feb;72(2):152-8. doi: 10.1001/jamaneurol.2014.3537.

Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort.

Author information

1
Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Boston, Massachusetts.
2
Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Boston, Massachusetts2Biostatistics Center, Massachusetts General Hospital, Brookline, Massachusetts.

Abstract

IMPORTANCE:

With multiple and increasingly effective therapies for relapsing forms of multiple sclerosis (MS), disease-free status or no evidence of disease activity (NEDA) has become a treatment goal and a new outcome measure. However, the persistence of NEDA over time and its predictive power for long-term prognosis are unknown.

OBJECTIVE:

To investigate NEDA during 7 years as measured by relapses, disability progression, and yearly magnetic resonance imaging (MRI).

DESIGN, SETTING, AND PARTICIPANTS:

Patients were selected from the 2200-patient Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital (CLIMB) cohort study. Patients were required to have an initial diagnosis of clinically isolated syndrome or relapsing-remitting MS and a minimum of 7 years of prospective follow-up that included yearly brain MRI and biannual clinical visits (nā€‰=ā€‰219). Patients were analyzed independent of disease-modifying therapy. Patients were classified as having early (recent-onset) MS if they were 5 years or less from their first MS symptom at enrollment or otherwise considered to have established MS (>5 years from onset).

MAIN OUTCOMES AND MEASURES:

NEDA was defined as a composite that consisted of absence of relapses, no sustained Expanded Disability Status Scale score progression, and no new or enlarging T2 or T1 gadolinium-enhancing lesions on annual MRI. Relapses, progression, and MRI changes were also investigated as individual outcomes.

RESULTS:

A total of 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. No differences were found in NEDA status between patients with early vs established MS. A dissociation was found between clinical and MRI disease activity. Each year, 30.6% (64 of 209) to 42.9% (93 of 217) of the cohort had evidence of either clinical or MRI disease activity but not both. NEDA at 2 years had a positive predictive value of 78.3% for no progression (Expanded Disability Status Scale score change ā‰¤0.5) at 7 years. Only minor improvement was found in the positive predictive values with additional follow-up of 1 to 3 years.

CONCLUSIONS AND RELEVANCE:

NEDA is difficult to sustain long term even with treatment. NEDA status at 2 years may be optimal in terms of prognostic value in the longer term. Our results provide a basis for investigating NEDA as an outcome measure and treatment goal and for evaluating the effect of new MS drugs on NEDA.

PMID:
25531931
DOI:
10.1001/jamaneurol.2014.3537
[Indexed for MEDLINE]

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