Despite widespread use of plasmapheresis for treating several different neurologic diseases, it has clearly proven efficacy for only acute inflammatory demyelinating polyneuropathy and chronic inflammatory demyelinating polyneuropathy, according to revised guidelines being released on Jan. 18 by the American Academy of Neurology.
Dr. Alexander Rae-Grant
An expert subcommittee of the academy also determined that plasmapheresis is probably effective for two other indications: polyneuropathy associated with immunoglobulin A and immunoglobulin G, and for managing exacerbations in relapsing forms of multiple sclerosis. The treatment also might be effective for fulminant demyelinating central nervous system disease, but for all other current neurologic applications of plasmapheresis the committee determined that either the evidence base was insufficient to judge its efficacy or the treatment is probably ineffective or proven ineffective (Neurology 2011;76:294-300).
"Plasmapheresis is one of the key, major treatments used in a variety of neurologic diseases, but it is relatively expensive, labor intensive, and intrusive with some risk to patients. That’s why it needs to be fully evaluated in a critical way," said Dr. Alexander Rae-Grant, a neurologist at the Mellen Center for Multiple Sclerosis of the Cleveland Clinic and a member of the AAN Therapeutics and Technology Assessment subcommittee that wrote the new guidelines.
"We need to look hard at the data and advise people and warn them when there is not good evidence of efficacy. It may help prevent having patients treated with something that has really not been shown effective," he said.
The subcommittee’s recommendations form the AAN’s first revision of its plasmapheresis recommendations since 1996 (Neurology 1996;47:840-3). For certain indications the intervening years produced new data, and in other cases the subcommittee produced a more contemporary assessment of the existing data.
"We look at the information more stringently over time. We’ve upgraded the quality of evidence that we expect from studies. We sometimes reclassified older studies and downgraded them because we now have a higher level of expectation," Dr. Rae-Grant said in an interview.
Despite this, "not many differences exist" between the new revision and the prior guidelines, he noted. In particular, the two most well-documented applications of plasmapheresis in neurology remain the same as 15 years ago: treatment of acute inflammatory demyelinating polyneuropathy (Guillain-Barr? syndrome), and short-term treatment of chronic inflammatory demyelinating neuropathy.
Perhaps the most controversial application of plasmapheresis in neurology is for myasthenia gravis, an indication that the subcommittee judged had insufficient evidence to either support or refute its efficacy when used for myasthenic crisis or myasthenia gravis prethymectomy. Despite the equivocal evidence base, "plasmapheresis is used at many medical centers for this indication," the guidelines noted.
"We tried very hard to stick with the evidence despite the practice pattern. We felt that, because plasmapheresis is so widely used [for these indications] we should comment on that use. Of all the indications, myasthenia gravis is the place where it has become common practice, even though when you look at the data it’s not strong. This is what people do, but it needs further evaluation.
"Experts in myasthenia gravis feel there are anecdotal data [in favor of its efficacy]. We tried to balance the expert concept and what the data show. Because our assessment was not in line with active practice, we tried to show [in the wording of the guidelines] that we were aware of this and thought about it," Dr. Rae-Grant said.
The subcommittee also found insufficient evidence for a role of plasmapheresis in treating Sydenham chorea and acute obsessive-compulsive disorder and tics in patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). It determined that good evidence exists to show that plasmapheresis is ineffective for treating polyneuropathy associated with immunoglobulin M, a monoclonal gammopathy of undetermined significance, and hence should not be used in these patients. The subcommittee also found strong evidence that plasmapheresis does not work in patients with chronic progressive or secondary progressive multiple sclerosis and should definitely not be used in these patients.
A final section of the guidelines highlighted seven recommendations for future research: the optimal plasma exchange protocol; the role for plasmapheresis in patients with mild acute inflammatory demyelinating polyneuropathy who have preserved ambulation and in those with this disorder who fail to respond to initial plasmapheresis or relapse after an initial response; the role for long-term plasmapheresis in patients with chronic inflammatory demyelinating neuropathy; adequately powered studies to assess the duration of benefit from plasmapheresis in patients with neuropathies associated with IgA or IgG gammopathy and in neuropathies associated with IgM gammopathy; the best way to use plasmapheresis in patients in myasthenic crisis and for myasthenia gravis prethymectomy; the treatment’s role in patients with fulminant demyelinating central nervous system disease that has not responded to corticosteroid treatment; and the role for plasmapheresis in patients with infectious complications following natalizumab treatment.