The statement was an effort by the International Advisory Committee on Clinical Trials in Multiple Sclerosis, which is jointly supported by the US National MS Society and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The Committee provides perspective and guidance in areas of interest to planning and implementing clinical trials for new agents for the treatment of MS.
“With this published statement, we’re encouraging the healthcare and regulatory community to use the terms as described for the different subtypes of MS and for describing disease activity,” noted Fred Lublin, MD (Icahn School of Medicine at Mount Sinai), who is senior author of the statement and two previous papers defining MS subtypes that were published in 1996 and 2013 under the auspices of the committee. “It’s critical not just for improving patient care, but also for selecting participants for clinical trials, so you are comparing apples to apples.”
Inconsistent use of the terms: The 2013 paper defined four categories of MS based on current clinical course: clinically isolated syndrome (an initial episode of neurological symptoms), relapsing-remitting MS, secondary progressive MS, and primary progressive MS. The paper also recommended adding terms to describe an individual’s current disease state, such as “active” (shown by relapse or changes on MRI) and “progression” (shown by worsening of disability independent of relapse activity). While the time period for the activity was not specified, it was recommended that an assessment be performed at least annually.
Since the 2013 paper was published, there has been confusion in the use of the terms describing a person’s current disease state and the terms have been used without reference to a timeframe. For example, in the prescription indications for recent MS therapy approvals, neither the European Medicines Agency nor the U.S. Food and Drug Administration specified a timeframe for determining disease activity. Moreover, the agencies defined activity differently; the European Medicines Agency defined “activity” as either clinical relapse or MRI-detected inflammation, whereas the U.S. Food and Drug Administration defined “activity” only in terms of relapses.
Clarifying definitions: The recently published statement reiterates the definition of “activity” as clinical relapses or imaging features of inflammatory activity, evaluated annually or over another specified interval. The definition of “progression” is reiterated as clinical evidence of disability worsening, independent of relapses, in individuals in a progressive phase, evaluated annually or over another specified interval. Also, the more general term “worsening” refers to any increase in impairment or disability as the result of residual deficits caused by relapses, or increasing disability during progressive phases of MS.
Future work: “As part of its ongoing activities, the committee plans to continue to reevaluate and refine course descriptors, especially when new evidence-based methods enable pathological distinctions between MS phenotypes, said Professor Alan Thompson, Chair of the International Advisory Committee on Clinical Trials in MS and Dean of University College London’s Faculty of Brain Sciences. “This would vastly improve prognosis, treatment choices, and the development of more selective therapies.”
Read the recently published open access statement, “The 2013 clinical course descriptors for multiple sclerosis: A clarification” by Fred D. Lublin, Timothy Coetzee, Jeffrey A. Cohen, Ruth Ann Marrie, Alan J. Thompson. Published online in Neurology on May 29, 2020.