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‘No evidence of disease activity’ has potential as a useful outcome in MS

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NEDA is important, but has hurdles

Although the study did not explore the impact of different treatment approaches, the ‘no evidence of disease activity’ measure (NEDA) is a necessary – albeit ambitious – benchmark that will likely become an important goal in MS care, according to Dr. Jaime Imitola and Dr. Michael K. Racke.

While the study suggests that NEDA is difficult to maintain long term, at 2 years it does have some prognostic value.

“Neurologists must start discussing the goal of disease activity–free status with their patients to take NEDA from the uniform environment of clinical trials to actual clinical practice,” they wrote.

Dr. Imitola and Dr. Racke are from the comprehensive multiple sclerosis center at Ohio State University, Columbus. Their comments come from an editorial accompanying the study on NEDA (JAMA Neurol. 2015;72:145-7). They reported having no relevant financial conflicts.


 

FROM JAMA NEUROLOGY

References

A longitudinal study of 215 patients with clinically isolated syndrome or relapsing-remitting multiple sclerosis showed that while 46% had achieved no evidence of disease activity at 1 year, only 7.9% maintained it after 7 years.

In the study of patients from the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women’s Hospital (CLIMB) cohort who had a minimum of 7 years of prospective MRI and clinical follow-up data, however, having no evidence of disease activity (NEDA) at 2 years had a positive predictive value of 78.3% for no progression at 7 years, according to Dr. Dalia L. Rotstein, then from the Brigham and Women’s Hospital and now with the St. Michael’s Hospital, Toronto, and her coauthors (JAMA Neurol. 2015;72:152-8).

The concept of NEDA is already used in diseases such as cancer and rheumatoid arthritis, but in multiple sclerosis (MS), it is still considered a secondary outcome measure, defined as the absence of new or enlarging T2 lesions or T1 gadolinium-enhancing lesions on MRI and no sustained Kurtzke Expanded Disability Status Scale (EDSS) score progression or clinical relapse, the authors said.

During the course of the study, clinical and MRI indicators of disease progress were dissociated, the investigators found. They reported that the percentage of patients who had no evidence of disease progression on one measure but not another ranged from 42.9% at year 2 to 30.6% at year 7. No MRI disease activity occurred in 23.5% at year 1 and in 14.8% at year 7, but the percentage of those who had no evidence of clinical disease activity stayed at about 15% at both time points.

“Although NEDA has the potential to become not only a key outcome measure of disease-modifying therapy but also a treat-to-target goal, it will require a comprehensive approach that integrates advances in MRI technology, linkage of blood and cerebrospinal fluid biomarkers, and a high degree of cooperation among investigators,” the authors wrote.

The study was partly supported by Merck Serono, and several authors declared grants, consultancies, advisory board positions, and speaking engagements with a range of pharmaceutical companies, including Merck Serono.

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