Experts Clarify Concepts of MS States to Improve Patient Care, Clinical Trials
An international committee of multiple sclerosis (MS) experts further clarified how guidelines, updated in 2013, should be used to classify this disease’s different states, and stressed the importance of measuring these states in a timely and consistent manner.
The group’s statement, “The 2013 clinical course descriptors for multiple sclerosis: A clarification,” was issued by the International Advisory Committee on Clinical Trials in Multiple Sclerosis and published in the journal Neurology.
Jointly supported by the U.S. National MS Society and the European Committee for Treatment and Research in MS, the committee (comprised of 25 MS experts) provides perspective and guidance for the planning of clinical trials of investigational MS therapies.
“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,” Fred Lublin, MD, the first author of this statement and of two previous committee-sponsored studies defining MS subtypes, said in a National MS Society news story.
“It’s critical not just for improving patient care, but also for selecting participants for clinical trials, so you are comparing apples to apples,” Lublin added. He is director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai’s Icahn School of Medicine in New York.
In a 2013 committee-sponsored study, MS specialists established four subtypes of MS, and recommended the addition of terms to describe a patient’s current disease state, such as “activity” and “progression,” and that the disease state be framed in time.
“Inclusion of a time frame is critical for effective clinical decision making,” the committee wrote in their statement. While the time period was not specified in the 2013 study, it was recommended that disease assessment be performed at least annually.
However, these terms have been inconsistently used and without reference to a time frame. In particular, regulatory authorities in Europe and the U.S. have used different definitions of disease activity in recent MS therapy approvals, including those given to Ocrevus (by Genentech), Mayzent (by Novartis), and Mavenclad (by EMD Serono; Merck KGaA outside North America).
Active disease was defined as the presence of either relapses or imaging-detected brain inflammation in Europe, but limited to relapses in the U.S. Agencies in neither region specified a timeframe for the disease activity.
This divergence can be problematic. “Variation in the application of the clinical course descriptors has the potential to create some confusion in clinical practice, the conduct of future clinical trials, and decisions by health authorities, insurers, and related entities concerning patient access to approved treatments,” the experts wrote.
Accordingly, the committee reiterated previous clinical recommendations and definitions of disease course terms, such as “active disease,” “progression,” and “worsening.”
The experts emphasized that “active disease” is defined as the presence of clinical relapses or brain imaging features of inflammatory activity, and “progression” as clinical evidence of disability worsening independent of any relapse activity in patients in a progressive course of MS (primary progressive MS or secondary progressive MS).
Both “active disease” and “progression” must be framed in time, either annually or in another prespecified time interval, they noted.
Further, the committee recommended that the term “worsening” be used to describe any increase in patients’ impairment or disability, regardless of being the result of relapses or of increasing disability occurring during progressive phases of the disease.
The statement is expected to further support the use of standardized terminology, the team wrote, which helps improve patient care and access to treatments. It also aids in selecting clinical trial participants and in translating trial results to clinical care.
Alan Thompson, MD, the committee’s chair and dean of the University College London’s Faculty of Brain Sciences, said: “as part of its ongoing activities, the committee plans to continue to reevaluate and refine course descriptors, especially when new evidence-based methods enable [clinical] distinctions between MS [subtypes].”
“This would vastly improve prognosis, treatment choices, and the development of more selective therapies,” Thompson added.
“We recognize that terminology and classification of the MS disease course are dynamic and will require redefining and clarifications as new data and measurement approaches become available,” the statement concluded. “To this end, the committee is planning for their next review of this topic for 2020 to revisit the clinical courses with a particular focus on progression and the contributors to progression.”