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Comment & Response
August 2014

Defining the New End Point for Multiple Sclerosis Treatment

Author Affiliations
  • 1Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany
  • 2Cognitive Psychology and Methodology, Basel University, Basel, Switzerland
  • 3Department of Neurology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany
JAMA Neurol. 2014;71(8):1056-1057. doi:10.1001/jamaneurol.2014.1542

To the Editor In their Viewpoint published in JAMA Neurology, Bevan and Cree1 proposed disease activity free status (DAFS) as a new end point in multiple sclerosis (MS) research. We strongly agree that with new effective drugs available to treat MS, we should aim for additional outcome parameters rather than being primarily focused on reducing the relapse rate. A complete stop of disease activity would be ideal; however, as the authors rightly outlined, DAFS is not yet well defined. The current definition includes the clinical variables of relapse and disability progression as measured by Expanded Disability Status Scale (EDSS) and the magnetic resonance imaging parameter of new or enlarging T2 lesions and gadolinium-enhancing lesions. This definition is very much driven by the radiographic marker, and the clinical scale is rather crude and oversimplified. The EDSS predominantly picks up walking disability but other factors, in particular neuropsychological functions, are underrepresented. In addition, disease progression in the low EDSS range is difficult to detect. However, immune intervention seems to be most promising in the early phases of MS when there is no or only little disability. After reaching an EDSS score of 3, the disease progression seems to be uniform and leads to pronounced neurologic deficits within several years.2 Thus, if we intend to achieve a complete disease silencing, then more sensitive tools than the EDSS to detect clinical changes are needed. Those tools should be applicable in everyday practice and not only as a research protocol to improve management of all patients with MS. Such a tool has been proposed including several tests for the domains relapse, disease progression, neuropsychology, and magnetic resonance imaging (Table).3 To ascertain practicability, these tests require only 20 minutes, of which 13 minutes are performed/explained by an MS nurse and 7 minutes are spent by the patient alone for questionnaires. Unfortunately, neither this nor any other tool has yet been validated or tested for clinical feasibility, and we currently follow the sensible assumption that the long-term outcome will be better if there is a DAFS. Thus, definition and validation of our measures for DAFS are requested for a much-needed treat-to-target strategy for patients with MS.

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