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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:
http://www.choosingwisely.org/doctor-patient-lists/american-academy-of-neurology/
The fully article is here:
http://www.neurology.org/content/ea...ract?sid=1d5b047e-12f0-4592-b460-098f78f2d078
A direct link to the PDF is here:
http://www.neurology.org/content/early/2013/02/20/WNL.0b013e31828aab14.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 experienced in 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 to patients with progressive MS and some do not. If a patient has progressive non-relapsing MS and have 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? What is your style of practice? Would you continue an injectible on a 65 year patient with no relapses or new MRI lesions in the last 20 years presuming she was steadily clinically progressing during this period while on treatment?
I thank you very much for you input.
#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:
http://www.choosingwisely.org/doctor-patient-lists/american-academy-of-neurology/
The fully article is here:
http://www.neurology.org/content/ea...ract?sid=1d5b047e-12f0-4592-b460-098f78f2d078
A direct link to the PDF is here:
http://www.neurology.org/content/early/2013/02/20/WNL.0b013e31828aab14.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 experienced in 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 to patients with progressive MS and some do not. If a patient has progressive non-relapsing MS and have 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? What is your style of practice? Would you continue an injectible on a 65 year patient with no relapses or new MRI lesions in the last 20 years presuming she was steadily clinically progressing during this period while on treatment?
I thank you very much for you input.
