This medical condition has either been superseded or has become inactive
| Specific Conditions |
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| Indication for Ig Use |
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| Level of Evidence | Clear evidence of benefit (Category 1) |
| Description and Diagnostic Criteria |
Multifocal motor neuropathy (MMN) is a relatively rare disorder characterised by slowly progressive, asymmetric, predominately distal limb weakness without sensory impairment. Weakness often begins in the arms and the combination of weakness, wasting, cramps and fasciculations may suggest a diagnosis of motor neuron disease. However, clinical examination may demonstrate that the pattern of weakness follows the distribution of individual nerves rather than a spinal segmental pattern. Investigations will typically show conduction block on nerve conduction studies. IgM anti-GM-1 antibodies have been reported in a large number of patients with MMN and provide confirmatory evidence but are not essential for the diagnosis. |
| Justification for Evidence Category |
The Biotext (2004) review found six low-quality case studies or crossover randomised controlled trials (RCTs) with a total sample size of 68 patients. A possible benefit of intravenous immunoglobulin (IVIg) treatment in these patients was observed, although five studies were not controlled. Frommer and Madronio (2006) identified a Cochrane systematic review including four RCTs. Thirty-four patients were randomly assigned to IVIg or placebo. IVIg treatment was superior to placebo in inducing an improvement in muscle strength. There was a trend (p=0.08) to reduced disability. In 2013 Han et al published a double blind placebo controlled study of IVIg treatment in 44 multifocal motor neuropathy (MMN) cases. Patients were randomized 1:1 to receive either double-blind treatment with IVIg followed by placebo for 12 weeks each, or the reverse. A significant difference (P = 0·005) in mean maximal grip strength was observed during IVIg treatment (increased 3·75 percent) compared to placebo (decline 31·4 percent) (Hahn et al 2013). A further review by Leger 2014 described the results of four small to moderate sized unblinded long-term follow-up studies of both treated and treatment naïve cases. Improvement was demonstrated in up to 70 percent of cases in grip strength and Medical Research Council (MRC) scores, confirming that IVIg is the most useful agent for initial and maintenance treatment of MMN. Consensus statements assert that IVIg is the only safe treatment demonstrated to be effective in patients with MMN. It is recommended in those who have significant disability. Dose and monitoring is similar to chronic inflammatory demyelinating polyneuropathy (CIDP). IVIg therapy is usually long term, but the minimum effective dose for each patient should be sought. Plasma exchange and steroids are ineffective and may cause deterioration. Regular maintenance doses of IVIg are needed. The National Guideline Clearinghouse (European Handbook of Neurological Management 2011) recommends IVIg as first-line treatment for definite MMN when disability is sufficient to warrant treatment. A trial of IVIg is not recommended for patients with exclusion criteria, or those without typical clinical or electrophysiological features, who are likely to have motor neuron disease (MND). |
| Diagnosis Requirements |
A diagnosis must be made by a Neurologist. |
| Qualifying Criteria for Ig Therapy |
First-line and maintenance therapy for multifocal motor neuropathy (MMN)
This indication should be used for new patients and those that have never trialled off from Ig therapy. For responding patients who have relapsed after weaning from Ig therapy please use the indication Relapse of multifocal motor neuropathy (MMN) patients within six months of commencement of trial off immunoglobulin therapy.
Review by a neurologist is required within four months of treatment and annually thereafter. Documentation of clinical efficacy is necessary for continuation of IVIg therapy. For patients in remission on maintenance therapy, a trial of weaning leading to cessation should be considered. If the patient relapses, they may be eligible for further Ig therapy under the indication Relapse of MMN patients within six months of commencement of a trail off Ig therapy. A subsequent trial of weaning leading to cessation might be considered after a further two years of Ig therapy. Relapse of multifocal motor neuropathy (MMN) patients within six months of commencement of trial off immunoglobulin therapy
This indication should be used for responding multifocal motor neuropathy (MMN) patients who have relapsed within six months of commencement of a trial off immunoglobulin therapy. For new patients and those that have never trialled off from Ig therapy, please use the indication First-line and maintenance therapy for MMN.
Review by a neurologist is required within four months of treatment and annually thereafter. Documentation of clinical efficacy is necessary for continuation of IVIg therapy. For patients in remission on maintenance therapy, a trial of weaning leading to cessation should be considered. If the patient relapses, again within six months of commencement of a trail off Ig therapy, they may be eligible for further Ig therapy under this indication. A subsequent trial of weaning leading to cessation might be considered after a further two years of Ig therapy. |
| Exclusion Criteria |
Presence of upper motor neuron signs Marked bulbar involvement Significant sensory impairment without an adequate alternative explanation Diffuse symmetric weakness during the initial weeks |
| Review Criteria for Assessing the Effectiveness of Ig Use |
First-line and maintenance therapy for multifocal motor neuropathy (MMN)
IVIg should be used for a maximum of four months (induction plus three maintenance cycles) before determining whether the patient has responded. If there is no benefit after this treatment, IVIg therapy should be abandoned.
Review by a neurologist is required within four months of treatment and annually thereafter. Documentation of clinical efficacy is necessary for continuation of IVIg therapy. For patients in remission on maintenance therapy, a trial of weaning leading to cessation should be considered. If the patient relapses, they may be eligible for further Ig therapy under the indication Relapse of MMN patients within six months of commencement of a trial off Ig therapy. A subsequent trial of weaning leading to cessation might be considered after a further two years of Ig therapy. Clinical effectiveness of Ig therapy can be assessed by: On review of the initial authorisation period
On review of a continuing authorisation period
Relapse of multifocal motor neuropathy (MMN) patients within six months of commencement of trial off immunoglobulin therapy
IVIg should be used for a maximum of four months (induction plus three maintenance cycles) before determining whether the patient has responded. If there is no benefit after this treatment, IVIg therapy should be abandoned.
Review by a neurologist is required within four months of treatment and annually thereafter. Documentation of clinical efficacy is necessary for continuation of IVIg therapy. For patients in remission on maintenance therapy, a trial of weaning leading to cessation should be considered. If the patient relapses, again within six months of commencement of a trail off Ig therapy, they may be eligible for further Ig therapy under this indication. A subsequent trial of weaning leading to cessation might be considered after a further two years of Ig therapy. Clinical effectiveness of Ig therapy may be assessed by: On review of the initial authorisation period
On review of a continuing authorisation period
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| Dose |
First-line and maintenance therapy for multifocal motor neuropathy (MMN)
The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.
Refer to the current product information sheet for further information on dose, administration and contraindications. Relapse of multifocal motor neuropathy (MMN) patients within six months of commencement of trial off immunoglobulin therapy
The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.
Refer to the current product information sheet for further information on dose, administration and contraindications. |
| Bibliography |
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| Association of British Neurologists 2005, Guidelines for the use of intravenous immunoglobulin in neurological diseases, The Association, London. Available from: http://www.theabn.org/media/docs/ABN%20publications/IVIg-guidelines-final-July05.pdf Biotext 2004, ‘Summary data on conditions and papers’, in A systematic literature review and report on the efficacy of intravenous immunoglobulin therapy and its risks, commissioned by the National Blood Authority on behalf of all Australian Governments. Available from: https://www.blood.gov.au/system/files/A-systematic-literature-review-and-report-on-the-efficacy-of-IVIg-therapy-and-its-risks.pdf The National Guideline Clearinghouse European Handbook of neurological management. 2nd Ed Vol 1 Oxford (UK); Wiley-Blackwell; 2011; p343-50. Gilhus, NE, Barnes, MR, Brainin, M 2010, ‘European Handbook of Neurological Management’, 2nd Edition, Volume 1, pp. 343-50, Oxford (UK), Wiley-Blackwell. Available from: https://www.wiley.com/en-us/European+Handbook+of+Neurological+Management%2C+2nd+Edition%2C+Volume+1-p-9781405185332 Federico, P, Zochodne, DW, Hahn, AF, et al 2000, ‘Multifocal motor neuropathy improved by IVIg: randomized, double-blind, placebo-controlled study’, Neurology, vol. 55, no. 9, pp. 1256–62. https://www.researchgate.net/publication/12239595_Multifocal_motor_neuropathy_improved_by_IVIg_Randomized_double-blind_placebo-controlled_study Frommer, M & Madronio, C, 2006, ‘The use of intravenous immunoglobulin in Australia. A report for the National Blood Authority, Part B: systematic literature review’, Sydney Health Projects Group, University of Sydney, Sydney, pp. 35–7. Graham, RC & Hughes, RA, 2006, ‘A Modified Peripheral Neuropathy Scale: The Overall Neuropathy Limitations Scale’, Journal of Neurology, Neurosurgery and Psychiatry, vol. 77,no. 8, pp. 973–976. https://www.ncbi.nlm.nih.gov/pubmed/16574730 Hahn, AF, Beydoun, SR, Lawson, V, et al 2013, ‘A controlled trial of intravenous immunoglobulin in multifocal motor neuropathy’, Journal of the Peripheral Nervous System, vol. 18, no. 4, pp. 321-30. https://www.readbyqxmd.com/read/24725024/a-controlled-trial-of-intravenous-immunoglobulin-in-multifocal-motor-neuropathy Kornberg, AJ, for the Asia–Pacific IVIg Advisory Board, 2004, ‘Bringing consensus to the use of IVIg in neurology. Expert consensus statements on the use of IVIg in neurology’, 1st edn, Asia–Pacific IVIg Advisory Board, Melbourne, pp. 30–4. Leger JM 2014, ‘Immunoglobulin (Ig) in multifocal motor neuropathy (MMN): update on evidence for Ig treatment in MMN’, Clinical and Experimental Immunology, vol. 178, pp. 42–44. https://onlinelibrary.wiley.com/doi/pdf/10.1111/cei.12505 Van den Berg-Vos, RM, Franssen, H, Wokke, JH, et al 2002, ‘Multifocal motor neuropathy: long-term clinical and electrophysiological assessment of intravenous immunoglobulin maintenance treatment’, Brain, vol. 125, no. 8, pp. 1875–86.https://www.ncbi.nlm.nih.gov/pubmed/12135977 Van Schaik, IN, Bouche, P, Illac, I, et al 2006, ‘European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy’, European Journal of Neurology, vol. 13, pp. 802–8.http://www.neuromuskularni-sekce.cz/res/file/archiv/Guidelines-Management-MMN.pdf Van Schaik, IN, van den Berg, LH, de Haan, R, et al 2005, ‘Intravenous immunoglobulin for multifocal motor neuropathy’, (Cochrane Review) in The Cochrane Library, Issue 2, John Wiley & Sons, Ltd, Chichester, UK.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004429.pub2/pdf |