Reply from authors to Khatri, McQuillen, Kaminski et al., Stork et al., and Mateen et al.
IreneCortese, guidelines@aan.com
V. Chaudhry, Baltimore, MD; D. Cornblath, Baltimore, MD; Y. So, Palo Alto, CA; F. Cantor, Bethesda
Submitted July 05, 2011
The updated plasmapheresis guideline is a systematic review of published trials of plasma exchange in a variety of neurologic conditions. These trials were rated according to AAN criteria for classification of evidence and the classification criteria have changed since the publication of the 1996 guidelines.
The panel identified those treatment practices validated by the classification of evidence and also identified situations where there was insufficient evidence (Level U rating), in order to guide future research in this area.
Regarding MG, no published controlled study exists that documents the efficacy of treatment with plasma exchange. Thus, despite the fact that plasma exchange is commonly used in myasthenic crisis and preoperatively prior to thymectomy, the absence of controlled studies precluded an evidence-based validation of this practice. A Cochrane review on this topic independently arrived at the same conclusion: "no adequate randomized controlled trials have been performed to determine whether plasma exchange improves the short-term or long-term outcome of MG." [14]
However, the guidelines should not be interpreted as evidence of a lack of efficacy of plasma exchange in MG. Understandably, it may be inappropriate to conduct a placebo-controlled, double-blind study of the use of plasma exchange in myasthenic crisis. The disconnection between the published guidelines and general clinical experience underscores that evidence-based guidelines should not be considered comprehensive or definitive guides to individual patient management. [15] This is especially true when the evidence pertinent to a clinical question is inadequate.
Likewise, for orphan diseases, such as retinocochleocerebral vasculopathy, or for treatment of common neurologic diseases in pregnancy, there is insufficient evidence to make a recommendation on the basis of AAN criteria for quality of evidence. Using the same criteria, the panel evaluated the double-blind, placebo-controlled study of MS by Khatri et al. [3] The panel's conclusion was similar to that reached in the guidelines that reviewed the disease-modifying therapies in MS in 2002 and 2008. [16] As in 2002, persistent uncertainties about the statistical interpretation of the data, together with more recent studies that failed to demonstrate a benefit of plasma exchange in progressive forms of MS, led to the classification of plasma exchange as "established ineffective" for this condition.
In the case of neuropathies associated with paraproteinemia, the panel concluded on the basis of a single Class I study that plasma exchange is “probably effective” for IgA- and IgG-associated neuropathy but “probably not effective” for IgM-associated neuropathy. As Dr. Stork points out, this study did not distinguish between axonal and demyelinating variants. This was recognized by the panel as an area requiring further research.
The AAN has consistently stated that use of its guidelines for determination of insurance reimbursement is inappropriate. [17] The purpose of AAN guidelines is to identify evidence for treatment and to note areas where evidence is lacking. The guidelines do not state that each patient must be treated in the same way. [15]
References
14. Gajdos P, Chevret S, Toyka K. Plasma exchange for myasthenia gravis. Cochrane Database of Systematic Reviews 2002, Issue 4. Art. No.: CD002275. DOI: 10.1002/14651858.CD002275.
15. Gronseth G, French J. Practice parameters and technology assessments: what they are, what they are not, and why you should care. Neurology 2008;71:1639–1643.
16. Goodin DS, Frohman EM, Garmany GP Jr, et al. Disease modifying therapies in multiple sclerosis: Subcommittee of the American Academy of Neurology and the MS council for Clinical Practice Guidelines. Neurology 2002;58:169–178.
17. Getchius TSD, Moses LK, French J, Gronseth GS, England JD, Miyasaki J. AAN Guidelines: a benefit to the neurologist. Neurology 2010;75:1126–1127.
Disclosures: See original article for full disclosure list.
The updated plasmapheresis guideline is a systematic review of published trials of plasma exchange in a variety of neurologic conditions. These trials were rated according to AAN criteria for classification of evidence and the classification criteria have changed since the publication of the 1996 guidelines.
The panel identified those treatment practices validated by the classification of evidence and also identified situations where there was insufficient evidence (Level U rating), in order to guide future research in this area.
Regarding MG, no published controlled study exists that documents the efficacy of treatment with plasma exchange. Thus, despite the fact that plasma exchange is commonly used in myasthenic crisis and preoperatively prior to thymectomy, the absence of controlled studies precluded an evidence-based validation of this practice. A Cochrane review on this topic independently arrived at the same conclusion: "no adequate randomized controlled trials have been performed to determine whether plasma exchange improves the short-term or long-term outcome of MG." [14]
However, the guidelines should not be interpreted as evidence of a lack of efficacy of plasma exchange in MG. Understandably, it may be inappropriate to conduct a placebo-controlled, double-blind study of the use of plasma exchange in myasthenic crisis. The disconnection between the published guidelines and general clinical experience underscores that evidence-based guidelines should not be considered comprehensive or definitive guides to individual patient management. [15] This is especially true when the evidence pertinent to a clinical question is inadequate.
Likewise, for orphan diseases, such as retinocochleocerebral vasculopathy, or for treatment of common neurologic diseases in pregnancy, there is insufficient evidence to make a recommendation on the basis of AAN criteria for quality of evidence. Using the same criteria, the panel evaluated the double-blind, placebo-controlled study of MS by Khatri et al. [3] The panel's conclusion was similar to that reached in the guidelines that reviewed the disease-modifying therapies in MS in 2002 and 2008. [16] As in 2002, persistent uncertainties about the statistical interpretation of the data, together with more recent studies that failed to demonstrate a benefit of plasma exchange in progressive forms of MS, led to the classification of plasma exchange as "established ineffective" for this condition.
In the case of neuropathies associated with paraproteinemia, the panel concluded on the basis of a single Class I study that plasma exchange is “probably effective” for IgA- and IgG-associated neuropathy but “probably not effective” for IgM-associated neuropathy. As Dr. Stork points out, this study did not distinguish between axonal and demyelinating variants. This was recognized by the panel as an area requiring further research.
The AAN has consistently stated that use of its guidelines for determination of insurance reimbursement is inappropriate. [17] The purpose of AAN guidelines is to identify evidence for treatment and to note areas where evidence is lacking. The guidelines do not state that each patient must be treated in the same way. [15] References
14. Gajdos P, Chevret S, Toyka K. Plasma exchange for myasthenia gravis. Cochrane Database of Systematic Reviews 2002, Issue 4. Art. No.: CD002275. DOI: 10.1002/14651858.CD002275.
15. Gronseth G, French J. Practice parameters and technology assessments: what they are, what they are not, and why you should care. Neurology 2008;71:1639–1643.
16. Goodin DS, Frohman EM, Garmany GP Jr, et al. Disease modifying therapies in multiple sclerosis: Subcommittee of the American Academy of Neurology and the MS council for Clinical Practice Guidelines. Neurology 2002;58:169–178.
17. Getchius TSD, Moses LK, French J, Gronseth GS, England JD, Miyasaki J. AAN Guidelines: a benefit to the neurologist. Neurology 2010;75:1126–1127.
Disclosures: See original article for full disclosure list.