The AAN has updated its guideline on the use of plasmapheresis to treat neurologic disorders. The guideline, which will appear in the Jan.18 edition of Neurology, was based on the scientific literature from 1995 through September 2009 as well as a review of the evidence used to formulate the previous guideline, issued in 1996.
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Neurology Today spoke with Irene Cortese, MD — a staff clinician in the Neuroimmunology Branch of the NINDS — who chaired the AAN panel that drew up the revised guideline. In a telephone interview, Dr. Cortese discussed the rationale for the revisions and what they mean for clinicians.
HAS THE USE OF PLASMAPHERESIS FOR NEUROLOGIC CONDITIONS CHANGED MUCH SINCE THE LAST GUIDELINE WAS ISSUED IN 1996?
The indications for plasmapheresis — or plasma exchange — have not in fact changed significantly. What has changed is that the evidence to support its use in different circumstances has either increased due to evidence being added or, in other cases, is no longer considered strong based on new criteria used to evaluate the strength of research.
Plasmapheresis is presumed to remove humoral factors (antibodies, cytokines, etc.) that might be contributing to and sustaining an inflammatory process, so it can be helpful in the treatment of a number of immune-mediated illnesses. The question is how can it or should it be used within the management of those diseases? The last guideline was in 1996, so it was time to look at it critically and determine what has changed.
WHAT ARE THE MAJOR DIFFERENCES BETWEEN THE 1996 GUIDELINE AND THE UPDATED VERSION?
Our review of previous studies led to the downgrading of some evidence, with the greatest impact on the evaluation of use of plasma exchange for myasthenia gravis. With the current criteria for rating evidence, available studies are insufficient to support or refute plasma exchange for that indication.
On the other hand, there is growing evidence that begins to define the indications of plasmapheresis in CNS demyelinating diseases, where there may be potential for a greater role. The same is true for acute inflammatory demyelinating polyneuropathy/Guillain-Barré syndrome (AIDP/GBS).
COULD YOU EXPLAIN SOME MORE ABOUT THE THINKING ON AIDP/GBS?
A review of older studies has stood the test of time — and therefore the evidence remains strong for use of plasma exchange in AIDP. This is especially true for more severe cases, for which there is more evidence. One new study did begin to address the role for plasma exchange in mild AIDP. Although the evidence is still limited, it suggests plasmapheresis is also beneficial for milder forms of this disease and it should be considered. This guideline did not address alter-native treatment options nor did it compare efficacy between them.
WHAT ABOUT THE USE OF PLASMAPHERESIS FOR CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY (CIDP)?
The evidence continues to support the use of plasma exchange for the short-term management of CIDP. But, according to the guideline, two studies showed “the beneficial effect is not sustained, with worsening beginning one to five weeks after the last plasmapheresis treatment.” This makes sense if you consider that plasma exchange does not actually correct or resolve the underlying disease process. If the underlying disease is acute and monophasic, it may help it resolve more quickly; if the underlying disease is chronic, plasma exchange may be beneficial transiently, but additional therapeutic interventions will be needed.
THE GUIDELINE SUPPORTS PLASMA EXCHANGE FOR NEUROPATHIES ASSOCIATED WITH IGA OR IGG MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE, BUT NOT WITH IGM. WHY DO THOSE RECOMMENDATIONS DIFFER?
These recommendations stem from the evidence. Speaking more generally, though, neuropathy associated with IgM doesn't typically have as robust a response to immunotherapy (including plasma exchange) as compared to IgG- or IgA-associated neuropathies, which tend to behave more like CIDP. This is probably telling us something about the underlying disease mechanisms — and probably is a good example of where research from bench to bedside and then back to bench might be critical for furthering our understanding of appropriate management of this disease.
WHAT ABOUT MULTIPLE SCLEROSIS AND OTHER CNS DEMYELINATING DISEASES?
There is potential but also a need to clarify the role of plasmapheresis in acute, fulminant demyelinating CNS disease — and specifically where along the treatment algorithm does plasmapheresis fall for each of these diseases. Currently for this indication it's really institutional experience and anecdotal evidence that guides its use. The guideline does note that based on strong evidence plasma exchange should not be offered for chronic (primary) progressive or secondary progressive MS, in which neurodegenerative processes likely prevail.
WHAT ABOUT MYASTHENIA GRAVIS (MG)?
Because the criteria for classification of evidence have become more stringent, we downgraded the recommendation for the use of plasma exchange in MG. I think this opens discussion about what we should do with this re-evaluation. Certainly myasthenic crisis does not lend itself to the type of study that would provide Class I evidence, so we may have to accept that for certain indications these standards are unlikely to be met.
WHAT AREAS DESERVE MORE RESEARCH?
Research is needed that confirms the role of plasma exchange in fulminant demyelinating CNS disease where corticosteroids have failed. In addition, the utility of plasma exchange in individual demyelinating diseases (for example, transverse myelitis) needs further study.
IS PLASMAPHERESIS OVERUSED BASED ON THE AVAILABLE EVIDENCE?
I don't think so. If anything, due to barriers such as access and need for specialists to perform it, it is probably used less often than it could be.
HOW DO YOU SEE PLASMA EXCHANGE FITTING INTO OVERALL TREATMENT PLANS AS NEW THERAPIES COME ON LINE?
Plasmapheresis is a powerful treatment option, especially in acute immune-mediated illnesses or for short-term management of patients with some chronic immune-mediated neurologic illnesses. As such it continues to have an important role that all neurologists need to be familiar with. •
FOR MORE ABOUT PLASMAPHERESIS IN NEUROLOGIC DISORDERS
Michelle L. Mauermann, MD, assistant professor of neurology at the Mayo Clinic in Rochester, MN, interviewed the lead guideline author Irene Cortese, MD, about what new evidence suggests about plasmapheresis in neurologic disorders. Download the Jan. 18 podcast on www.neurology.org.
Cortese I, Chaudhry V, Rae-Grant A, et al. Evidence-based guideline update: Plasmapheresis in neurologic disorders. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2011; 76: 294–300.