The choosing wisely guidelines by the AAN

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The choosing wisely guidelines by the AAN

Postby centenarian100 » Mon Dec 02, 2013 3:23 pm

Earlier this year, the American Academy of Neurology published five recommendations regarding common "mistakes" made by neurologists.

#4 is as follows:

"Don’t prescribe interferon-beta or glatiramer acetate to patients with disability from progressive, non-relapsing forms of multiple sclerosis...

Interferon-beta and glatiramer acetate do not prevent the development of permanent disability in progressive forms of multiple sclerosis. These medications increase costs and have frequent side effects that may adversely affect quality of life."

The list of recommendations can be found here: ... neurology/

The full article is here: ... 8f78f2d078

A direct link to the PDF is here: ... 4.full.pdf html

I think you may need a password to access the online green journal

Here is a brief background for those who are less knowledge about Multiple sclerosis:

There is evidence in ongoing inflammation in all forms of multiple sclerosis (oligoclonal bands in CSF, meningeal lymphoid aggregates in secondary progressive MS found in some autopsy cases, inflammatory cells in normal appearing white matter).

However, there have been multiple failed trials regarding immunosuppressants in progressive forms of MS (primary progressive MS, secondary progressive MS) including potent myeloablative chemotherapies followed by bone marrow transplantation.

It is believed by many that progressive MS is mediated more by degenerative processes such as secondary axonal injury or metabolic/mithochondrial failure than by inflammation.

In clinical practice, some clinicians use injectibles such as beta-interferons and glatiramer for patients with progressive MS and some do not. If a patient has progressive non-relapsing MS and has not had relapses, new T2 bright lesions on MRI, or gadolinium enhancing lesions on MRI for many years (which often happens around age 50-55 regardless on age at disease onset), some clinicians will stop injectibles and focus on symptomatic therapies. However, there are reports of patients who have had relapses or more rapid deterioration after stopping therapy, so some experts would advise against stopping therapy.

The sources listed for the recommendation are here:

Rice GP, Incorvaia B, Munari L, et al. Interferon in relapsing-remitting multiple sclerosis. Cochrane Database Syst Rev 2001;4:CD002002.
La Mantia L, Munari LM, Lovati R. Glatiramer acetate for multiple sclerosis. Cochrane Database Syst Rev 2010;5:CD004678.
La Mantia L, Vacchi L, Di Pietrantonj C, et al. Interferon beta for secondary progressive multiple sclerosis. Cochrane Database Syst Rev 2012;1:CD005181.
Rojas JI, Romano M, Ciapponi A, Patrucco L, Cristiano E. Interferon beta for primary progressive multiple sclerosis. Cochrane Database Syst Rev 2009;1:CD006643.

When the recommendation was published, it passed by a small majority (34% disagreed), and many experts were upset. In fact, was not initially reviewed by the MS seciton.

Here is an example of a response to the recommendation with citations:

Recommendation #4 in the Choosing Wisely article by Langer-Gould et al. [1] suggests that interferons and glatiramer acetate should not be used in patients with progressive, non-relapsing forms of the illness. This recommendation fails to recognize clear benefits in subsets of both secondary progressive [2] and primary progressive [3] patients, especially in those with history of recent relapse, enhancing lesions on scans, and perhaps mostly, younger progressive patients. In addition, what little evidence that does exist on discontinuation of disease-modifying therapies (DMT) in progressive MS suggests that stopping either interferons [4] or natalizumab [5] may be associated with significant recurrence of disease activity. In reality, there is no large, multi-year study designed to examine if discontinuation of DMT in MS, in any context, is safe and not associated with significant recurrence of disease activity. As most patients with progressive forms of MS (especially secondary progressive MS) will likely already be on a DMT when a decision is potentially made to not use a DMT, a recommendation to simply not use MS medications is premature and potentially dangerous. This issue requires not only more discussion, but a lot more data.

1. Langer-Gould AM, Anderson WE, Armstrong MJ, et al. The American Academy of Neurology's top five choosing wisely recommendations. Published online before print February 20, 2013.
2. Kappos L, Weinshenker B, Pozzilli C, et al. Interferon-beta-1b in secondary progressive MS: A combined analysis of the two trials. Neurology 2004;63:1779-1787.
3. Hawker K, O'Connor P, Freedman MS, Calabresi PA, Antel J, Simon J, Hauser S, Waubant E, Vollmer T, Panitch H, Zhang J, Chin P, Smith CH; OLYMPUS trial group. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo- controlled multicenter trial. Ann Neurol 2009;66:460-471
4. Wu S, Dastidar P, Kuusisto H, Ukkonen M, Huhtala H, Elovaara I, Increased disability and MRI lesions after discontinuation of IFN beta-1a in secondary progressive MS. Acta Neurol Scan 2005;112:242-247.
5. Miravalle A, Jensen R, Kinkel RP. Immune reconstitution inflammatory syndrome in patients with multiple sclerosis following cessation of natalizumab therapy. Arch Neurol 2011;68:186-191.

What is your opinion regarding this recommendation? Is it reasonable to take injectibles if you are 65 years old with MS with no relapses or new MRI lesions in the last 20 years (presuming steady clinical progression during this period while on treatment)?

I know that it is psychologically more powerful to be active and vigilant in fighting disease, but if the treatment isn't helpful, should we accept it? The $50,000/year for these medicaitons could be used for rehab, symptomatic treatments, assistive devices, paying caretakers, and future multiple sclerosis research. If a 55 year old takes copaxone every day and then dies at age 75 of an unrelated heart attack, that is $1,000,000 dollars solely in medication expenses. If the medication isn't chaning the course of the disease, should we continue to take it?

I thank you very much for you input.
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Re: The choosing wisely guidelines by the AAN

Postby NHE » Tue Dec 03, 2013 12:24 am

centenarian100 wrote:If the medication isn't chaning the course of the disease, should we continue to take it?

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Re: The choosing wisely guidelines by the AAN

Postby MSandI » Tue Dec 03, 2013 5:30 pm

I am puzzled by these questions myself. The one thing that I do want to add is that dmd does not cure ms, but its purpose is to slow the progression of the disease. My question is how do you know if it is working (meaning slowing the progression down, changing the course of the disease). So to stop it because it is not working, how do you come to that conclusion? I have been on avonex for sometime now, and just recently stopped for a couple of reasons. I cannot say that it worked or did not work on my ms. My neuro wants me to try tecfidera, but I am still sitting on the fence trying some advice I have found in this forum.
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Re: The choosing wisely guidelines by the AAN

Postby cheerleader » Tue Dec 03, 2013 6:21 pm

Hi to both Centenarian and Ann--
In the past decade or so, the monitoring of MS disease progression has slowly changed, from using white matter lesions and relapses to noting that loss of gray matter is a better indicator of disease progression.
Grey matter atrophy occurs in the earliest stages of MS, progresses faster than in healthy individuals, and shows significant correlations with MRI lesion load, cognitive function and measures of physical disability; indeed, brain atrophy is the best predictor of subsequent disability and can be readily measured using MRI.

So, as you've both pointed out, there's a problem. How can you tell is a dmd is "working"? I would ask a few questions of your neurologist.
Am I still RRMS? Is this why you are recommending a dmd or Tecfidera, because I have an inflammatory disease process?
How does my gray matter look on MRI? Is my third ventricle enlarged, have I lost mass in my thalamus and brain stem?
Another thing to discuss is how you are doing in terms of progression. Have you lost mobility? Do you have new disabilities? Or is your disease stable.

Inflammation is part of RRMS, and that is what the dmds were created to address, but we do not see inflammation in older individuals or those with progressive MS. In these individuals, it appears that preserving gray matter is more important. And none of the dmds were created or trialled to do this.

But exercise can increase gray matter in those with MS, with no side effects. ... otion.html

Lots to think about! Good luck,
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
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