Author Topic: Remission (DAFS or disease-activity free status) as a goal in MS?  (Read 138 times)

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Offline agate

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From MedPage Today, January 8, 2014:

Quote
Striking a Nerve: Remission as an MS Treatment Goal


By John Gever, Deputy Managing Editor, MedPage Today

Is it time to set disease remission as a treatment goal in relapsing-remitting multiple sclerosis?

Carolyn Bevan, MD, and Bruce Cree, MD, PhD, of the University of California San Francisco, pretty much said so in a Viewpoint essay published Monday in JAMA Neurology. Except they stopped short of using the word "remission."

Instead, they advocated "disease activity free status," or DAFS, as an endpoint to include in future MS treatment trials, which some day might become the standard primary endpoint.

DAFS has been defined as the absence of clinical relapse symptoms along with lack of evidence of disease activity in MRI scans. It has been reported in some post-hoc analyses of phase III trial data for drugs including natalizumab (Tysabri), fingolimod (Gilenya), and dimethyl fumarate (BG-12, Tecfidera).

Those, of course, were industry-funded studies. DAFS gained more credibility when it was included as an outcome measure in the National Institutes of Health-funded CombiRx study of combined glatiramer acetate (Copaxone) and interferon-beta-1a (Avonex).

Bevan and Cree noted that, in the five studies analyzed thus far, DAFS was achieved by 28% to 44% of patients receiving one of the tested treatments -- indicating that it is indeed a feasible treatment goal.

Fine, but what's wrong with "remission" as the name for it? Bevan and Cree argued that its use in other chronic disorders such as rheumatoid arthritis had brought connotations that cannot be supported in MS.

"Rheumatoid arthritis is an inflammatory disease for which the treat-to-target approach inherently makes sense. In contrast, MS has both inflammatory as well as degenerative components," they wrote.

"It is not known if applying a treat-to-target strategy to the inflammatory aspect of MS will have an effect on the degenerative processes that underlie disease progression. Because MS evolves over decades, the effect of DAFS on long-term disability has yet to be evaluated."

True enough. Nevertheless, as a professional wordsmith, I see no substantive difference in saying a patient is "in remission" versus "free of disease activity." Certainly in the cancer world, "remission" carries no connotation of permanence.

Bevan and Cree pointed out another, more immediate problem with incorporating remission or DAFS, whichever one prefers, into clinical trial designs, which is how to include disability progression. Surely some measure of disability progression ought to be part of any definition of freedom from disease activity, the researchers argued.

The problem is that the current standard measure, the Expanded Disability Status Scale (EDSS), has been used in different ways in different trials. Measured on a categorical scale, it has also been criticized as excessively subjective and for emphasizing certain forms of disability over others.

In part because MS relapses and sustained EDSS-measured progression are both usually infrequent, DAFS as defined in the previous studies has been driven by MRI findings, which Bevan and Cree suggested was problematic.

"Before DAFS becomes the new standard for efficacy in MS therapeutic trials, its prognostic utility in assessing MS disability will need to be established," they wrote.

But, as they also noted, the fact that this conversation is even possible "highlights the remarkable progress in MS therapeutics over the past 2 decades."

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Striking a Nerve is a blog by John Gever for readers interested in neurology and psychiatry.

The article can be seen here.
« Last Edit: January 18, 2014, 02:18:41 pm by agate »
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.