New AAN Guideline on IVIg in Neuromuscular Disorders

Megan Brooks

March 26, 2012

March 26, 2012 — The American Academy of Neurology (AAN) has published an evidence-based guideline on the use of intravenous immunoglobulin (IVIg) in the treatment of neuromuscular disorders.

Developed by the Therapeutics and Technology Assessment Subcommittee of the AAN, the document, along with a 2-page summary for clinicians, is published in the March 27 issue of Neurology.

"Treatment with IVIg has increased and neurologists, and other clinicians who treat neuromuscular disease, should be aware of the data supporting its use," guideline lead author Huned S. Patwa, MD, from Yale University and the Veterans Affairs Connecticut Healthcare System, New Haven, told Medscape Medical News.

Strong Evidence

IVIg is used to treat a range of immune-mediated neurologic disease. It's approved by the US Food and Drug Administration (FDA) for use in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating syndrome (CIDP), but it's often used for non–FDA-approved indications, the guideline authors note.

The guideline summarizes the evidence and makes recommendations regarding IVIg use in treating patients with specific neuromuscular disorders.

For GBS, there is strong (level A) evidence of efficacy in adults but insufficient evidence to support or refute the effectiveness of IVIg in children, the guideline states. "Many experts consider it reasonable treatment to use IVIg for GBS in children given its effectiveness in the same disease in adults," the authors note.

The guideline also states that IVIg is as efficacious as plasmapheresis and should be offered for treating GBS in adults, but it recommends against combining IVIg with plasmapheresis for treatment of GBS (moderate evidence, level B). There is insufficient evidence to recommend methylprednisolone in combination with IVIg. There is also insufficient evidence to make a recommendation on the optimal dose of IVIg for GBS.

Strong (level A) evidence also exists for the efficacy of IVIg in CIDP, the guideline notes. However, it also alerts clinicians that dosing, frequency, and duration of IVIg for CIDP may vary depending on the clinical assessment and that evidence is insufficient to address the comparative efficacy of other CIDP treatments (eg, steroids, plasmapheresis, and immunosuppressants).

Additionally, the guideline notes that experts have identified possible overuse of IVIg in long-term care of CIDP. "We were unable to evaluate this question using available randomized trial data," the authors note.

Moderate Evidence

According to the guideline, IVIg is "probably effective and should also be considered" in the treatment of myasthenia gravis (MG). The authors note that the MG recommendation (moderate evidence, level B) is based largely on studies involving moderately or severely affected patients. "The benefits and risks of this medication should be weighed carefully in patients with mild MG," they say, adding, "Further studies of IVIg efficacy in MG are warranted due to the few randomized trials and small study size to date."

There is also moderate (level B) evidence to consider IVIg for multifocal motor neuropathy (MMN), according to the guideline. "MNN is a chronic disease requiring ongoing treatment. No data are available to address optimal treatment dosing, interval and duration," the guideline states.

IVIg is possibly effective and may be considered for treating nonresponsive dermatomyositis in adults and Lambert-Eaton myasthenic syndrome (weak evidence, level C). There is insufficient evidence to support or refute use of IVIg in the treatment of neuropathy associated with IgM paraprotein, inclusion-body myositis, polymyositis, diabetic radiculoplexoneuropathy, or Miller Fisher syndrome or in the routine treatment of postpolio syndrome or in children with GBS (level U).

Dr. Patwa told Medscape Medical News, "IVIg is relatively safe in selected patients, but there remains concern for thrombotic events and renal failure in rare cases." The guideline advises individual patient risk assessment for adverse events (AEs) when IVIg therapy is considered.

It also notes that in 22 prospective studies reviewed, 18 recorded the number of serious and minor AEs from 632 patients receiving IVIg at a total dose of 2.0 to 2.5 g/kg. "There were no IVIg-related deaths in these studies. Most studies concluded that IVIg was well-tolerated and AEs were either transient or manageable," the guideline notes.

The most common IVIg-related AEs included headache (16.1%), fever (6.6%), mild hypertension (4.6%), chills (3.3%), nausea (3.2%), asthenia (1.4%), arthralgia (1.3%), anorexia (1.1%), dizziness (1.1%), malaise (1.1%), and transient hyperglycemia (1.1%).

Serious AEs related to IVIg were rare and included aseptic meningitis (n = 3), urticaria (n = 2), heart failure (n = 1), myocardial infarction (n = 1), and renal failure (n = 1), they say. "These findings do not exclude the possibility of rare AEs such as stroke and thrombotic events, which have been previously reported with IVIg," the authors emphasize.

"Evidence based guidelines," Dr. Patwa told Medscape Medical News, "are meant as a guide for clinicians based on current evidence available. Individual patient decisions need to be made on clinical circumstances, atypical presentations, comorbidities and previous response to therapy," he added.

Recommendations 'Appropriate'

The guideline also notes that more data are needed on the efficacy of IVIg as compared with other therapies. "There are several areas for potential research, including optimal dosing and timing for IVIg administration, role of adjunctive treatments and comparative treatment trials," Dr. Patwa said.

"In addition there are numerous conditions such as IgM paraprotein-associated neuropathy, inclusion body myositis, polymyositis, diabetic radiculoplexoneuropathy and Miller Fisher syndrome for which there is insufficient evidence and further research is needed," he added.

John T. Kissel, MD, director of the Division of Neuromuscular Medicine at Ohio State University Medical Center in Columbus, who was not involved in development of the guideline, told Medscape Medical News that it's "an excellent summary of a very complicated area."

"The authors have very nicely and completely summarized the literature and the evidence, and their conclusions and recommendations seem appropriate and very much in line with current thinking from most of us in the neuromuscular community," he added.

"The article should also help get insurance authorizations to help pay for this relatively expensive therapy, as that is sometimes a difficult issue in regards to IVIg therapy," Dr. Kissel said.

Neurology. 2012;78:1009-1015. Abstract

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