Immunotherapy for IgM anti-myelin-associated glycoprotein paraprotein-associated peripheral neuropathies.
BACKGROUND
Serum monoclonal anti-myelin associated glycoprotein antibodies may be pathogenic in some people with IgM paraprotein and demyelinating neuropathy. Immunotherapies aimed at reducing the level of these antibodies might be expected to be beneficial.


OBJECTIVE
To examine the efficacy of any form of immunotherapy in reducing disability and impairment resulting from IgM anti-myelin associated glycoprotein paraprotein-associated demyelinating peripheral neuropathy.


METHODS
We searched the Cochrane Neuromuscular Disease Group Register (March 2005), MEDLINE (January 1966 to March 2005) and EMBASE (January 1980 to March 2005) for controlled trials. We also checked bibliographies and contacted authors and experts in the field.


METHODS
We included randomised or quasi-randomised controlled trials of participants of any age treated with any type of immunotherapy for anti-myelin-associated glycoprotein antibody associated demyelinating peripheral neuropathy with monoclonal gammopathy of undetermined significance of any severity. Our primary outcome measure was change in the Neuropathy Impairment Scale or Modified Rankin Scale at six months after randomisationSecondary outcome measures were: Neuropathy Impairment Scale or the Modified Rankin Score at 12 months after randomisation; ten-metre walk time, subjective clinical scores and electrophysiological parameters at six and 12 months after randomisation; IgM paraprotein levels and anti-myelin associated glycoprotein antibody titres at six months after randomisation and adverse effects of treatments.


METHODS
We identified eight possible trials. Of these, five randomised controlled trials were included after discussion between the authors. One author extracted and the other checked the data. No missing data could be obtained from trial authors.


RESULTS
The five eligible trials (97 participants) tested intravenous immunoglobulin, interferon-alpha or plasma exchange. Only two, of intravenous immunoglobulin, had comparable interventions and outcomes but both were short-term. There were no significant benefits of the treatments used in the outcomes predefined for this review, but not all the predefined outcomes were used in every included trial. Intravenous immunoglobulin showed benefits in terms of improvement in Modified Rankin Scale at two weeks and 10-metre walk time at four weeks. Serious adverse effects of intravenous immunoglobulin are known to occur from observational studies but none were encountered in these trials.


CONCLUSIONS
There is inadequate reliable evidence from trials of immunotherapies in anti-myelin associated glycoprotein paraproteinaemic neuropathy to recommend any particular immunotherapy treatment. Intravenous immunoglobulin is relatively safe and may produce some short-term benefit. Large well-designed randomised trials of at least six to 12 months duration are required to assess existing or novel therapies.
Lunn
M P T
MP
National Hospital for Neurology and Neurosurgery, Department of Neurology, Queen Square, London, UK, WC1N 3BG. michael.lunn@kcl.ac.uk
Nobile-Orazio
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D003711:Demyelinating Diseases / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D010265:Paraproteinemias / Q000276:immunology; D010266:Paraproteins / Q000276:immunology*; D010523:Peripheral Nervous System Diseases / Q000276:immunology / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic
D007075:Immunoglobulin M; D018992:Myelin-Associated Glycoprotein; D010266:Paraproteins