Journal expresses concern over flawed multiple sclerosis treatment guideline

neurology may13coverThe journal Neurology has issued an Expression of Concern over recommendations it published earlier this year regarding the treatment of multiple sclerosis.

The journal’s website received multiple comments from clinicians expressing their own concern about the flawed recommendation, which was published as part of a paper titled “The American Academy of Neurology’s Top Five Choosing Wisely recommendations.” The problematic item was number 4:

The Working Group submitted 5 neurologic recommendations to the AAN Practice Committee and Board of Directors; all 5 were approved by both entities in September 2012. Recommendation 1: Don’t perform EEGs for headaches. Recommendation 2: Don’t perform imaging of the carotid arteries for simple syncope without other neurologic symptoms. Recommendation 3: Don’t use opioids or butalbital for treatment of migraine, except as a last resort. Recommendation 4: Don’t prescribe interferon-β or glatiramer acetate to patients with disability from progressive, nonrelapsing forms of multiple sclerosis. Recommendation 5: Don’t recommend carotid endarterectomy for asymptomatic carotid stenosis unless the complication rate is low (<3%).

But a group of posters identifying themselves as “David H. Mattson, Indianapolis, IN; Robert P. Lisak, Detroit, MI; David E. Jones, Charlottesville, VA,” wrote:

As representatives of the multiple sclerosis (MS) section of the AAN we have major concerns about recommendation 4 of the AAN Choosing Wisely Working Group: “don’t prescribe interferon-beta or glatiramer acetate to patients with disability from progressive, nonrelapsing forms of multiple sclerosis”. [1] Due to an administrative oversight at the AAN, this recommendation was never reviewed by the Executive Committee of the MS section, contrary to what was stated to have occurred in the Methods. This article is not an evidence-based guideline and should not be construed as such. This is an oversimplified recommendation that we strongly feel needs to be more nuanced. Progressive MS patients with superimposed relapses can still benefit from these agents, as acknowledged in the text of the article. Progressive patients who are on one of these agents and having no relapses are likely obtaining a partial treatment benefit and should remain on the agent. Progressive patients with gadolinium- enhancing central nervous system lesions can benefit from treatment. [2] Progressive MS shares pathophysiology with relapsing MS, rendering these labels arbitrary and artificial in clinical decision making. [3] The treatment of a complex disease like MS requires clinical judgment that cannot be reduced to platitudes!

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. Cook SD, Dhib-Jalbut S, Dowling P, et al. Use of magnetic resonance imaging as well as clinical disease activity in the clinical classification of multiple sclerosis and assessment of its course. International Journal of MS Care 2012;14:105-114.

Similar remarks came from “John R. Corboy, Professor, Neurology, University of Colorado School of Medicine,” who wrote:

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 (1) and primary progressive (2) 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 DMTs in progressive MS suggests that stopping either interferons (3) or natalizumab (4) may be associated with significant recurrence of disease activity. In reality, there is no large, multi-year study designed to examine if discontinuation of DMTs 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 SPMS) 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. 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.

2. 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

3. 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.

4. 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.

The authors of the flawed recommendation issued an online response, in which they apologized for the mixup:

We apologize for our inadvertent failure to obtain review from the AAN MS Section for the Choosing Wisely recommendations before the AAN Board of Directors approved the list. AAN staff reached out to relevant AAN Sections in August 2012 to review the list of recommendations, and it was an inadvertent error that the email did not reach the MS Section. When we were notified of this omission, we sent the MS recommendation and supporting text to the full MS Section for comment in April 2013. When that comment period ends May 2, 2013, the AAN’s Choosing Wisely work group will reconvene on May 8, 2013, to evaluate responses and respond to Mattson et al. and Corboy.

Neurology now has issued the following statement:

The editors express concern about a recommendation in the report “The American Academy of Neurology’s Top Five Choosing Wisely recommendations” (Neurology® 2013 Feb 20 [Epub ahead of print]; DOI: 10.1212/WNL.0b013e31828aab14). The Methods section contained wording indicating that the AAN Working Group sent the final 7 candidate recommendations to relevant AAN Sections and Committees, specialty societies, and patient advocacy organizations for review before voting on the final recommendations. In fact, as the result of an oversight by AAN staff, the Multiple Sclerosis Section of the AAN was not asked for their input, which was relevant for the fourth recommendation, “Don’t prescribe interferon-β or glatiramer acetate to patients with disability from progressive, nonrelapsing forms of multiple sclerosis.” Several members of the Multiple Sclerosis Section have responded in Neurology‘s WriteClick online correspondence with major concerns about this recommendation. Further evaluation is under way to determine whether the authors will change the recommendation after review by the Section.

The American Academy of Neurology, which publishes Neurologypromoted its Choosing Wisely recommendations — an initiative of the American Board of Internal Medicine and various specialty groups — when they initially appeared. Will it issue a new release to reflect the amended item?

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