The AAN has released a new evidence-based guideline on the efficacy of IV immunoglobulin (IVIg) — used to treat a range of immune-mediated neurological diseases — for neuromuscular disorders, based on a comprehensive review of the literature by the AAN Therapeutics and Technology Assessment Subcommittee in the 43-year period between 1966 and 2009. The review was published in the March 27 print issue of Neurology.
Lead author Huned S. Patwa, MD, associate professor of neurology at Yale University School of Medicine and chief of the Neurology Service at VA CT Healthcare System, talked to Neurology Today about the findings, recommendations, and further research indications expounded upon in this review. Dr. Patwa is involved in research in neuropathy, ALS, myasthenia gravis and neuromuscular disorders at Yale University.
WHAT ARE THE SIGNIFICANT FINDINGS FOR TREATMENT OF NEUROMUSCULAR DISORDERS WITH IVIG?
There is strong evidence [Level A] to support the use of IVIg for the treatment of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). We also found moderate evidence to support the use of IVIg for myasthenia gravis, but that seems to be limited to the treatment of moderate to severely ill patients as well as for multifocal motor neuropathy [Level B].
Evidence is insufficient to support the use of IVIg in the treatment of paraprotein neuropathy, inclusion body myositis, polymyositis, diabetic radiculoplexoneuropathy, or Miller Fisher syndrome.
HOW WOULD NEUROLOGISTS USE THESE GUIDELINES IN PRACTICE?
Neurologists are generally familiar with the use of IVIg for the treatment of neuromuscular diseases. However, some of them may not know the evidence that corroborates these uses. This review provides the data that support these treatments. In other cases, this review points out the gap in information to support use and helps guide neurologists in the direction where further research is needed.
WHAT ARE SOME OF THE SIDE EFFECTS OF THE TREATMENT?
We reviewed studies that recorded both minor and serious adverse events and discovered that there were a very limited number of adverse events. The serious adverse events include myocardial infarction, aseptic meningitis, heart failure, and renal failure. More common adverse events include headache, fever, nausea, mild hypertension, chills, and asthenia. Neurologists who treat patients with IVIg should be aware of the risks of thrombotic events and renal failure.
WHAT ARE SOME OF THE ALTERNATE TREATMENTS, AND HOW DO THEY MEASURE UP?
One of the alternative treatments is plasmapheresis, which was evaluated in a recent evidence-based AAN guideline as well. [See http://bit.ly/xV9Cs8.] We know that plasmapheresis and IVIg are equally effective in the treatment of GBS. Another treatment that we looked at was the addition of steroids, particularly methylprednisolone for GBS, but we found that the evidence was inadequate to make a recommendation for adding steroids.
THE GUIDELINES MENTION THAT THE BENEFIT FROM IVIG IS OFTEN SHORT-LIVED. WHY IS THIS? HAS THIS BEEN ADDRESSED BY RESEARCH?
That's correct. IVIg is short-lived and requires ongoing treatment. There are inadequate studies to look at long-term use of IVIg for the treatment of neuromuscular diseases, except for CIDP in which we specifically made a recommendation that it is efficacious for long-term treatment based on a long-term clinical trial. Data to support optimal dosing and timing are still lacking.
WHERE SHOULD FURTHER RESEARCH BE DONE?
We reviewed a number of conditions where evidence is inadequate to make a determination (Level U), such as inclusion body myositis, IgM paraproteinemic neuropathy, polymyositis, diabetic radiculoplexoneuropathy, and Miller Fisher syndrome. Further research is needed on these conditions.
Other treatment modalities are available for many of the diseases that we discussed, so comparative studies would certainly be helpful. Long-term studies would also allow us to understand the benefits of treatment with IVIg in chronic conditions. Studies to assess optimal timing, dosing and duration of treatment would be welcomed. All of these areas are ripe for further research and study.
• Patwa HS, Chaudhry V, So YT, et al. Evidence-based guideline: Immune globulin intravenous (IGIV) in the treatment of neuromuscular disorders. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2012; 78:1009-1015.