| Specific Conditions |
|
| Indication for Ig Use |
|
| 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 MMN cases. Patients were randomised 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 Indication 2: Relapse of multifocal motor neuropathy (MMN) patients within six months of commencement of trial off immunoglobulin therapy.
Review by a neurologist is required within 4 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 Indication 2: 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 2 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 6 months of commencement of a trial off immunoglobulin therapy. For new patients and those that have never trialled off from Ig therapy, please use Indication 1: First-line and maintenance therapy for MMN.
IVIg should be used for a maximum of 4 months (induction plus 3 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 4 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 6 months of commencement of a trial 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 2 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 4 months (induction plus 3 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 4 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 Indication 2: 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 2 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 4 months (induction plus 3 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 4 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 6 months of commencement of a trial 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 2 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
|
| 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 |
|---|
Association of British Neurologists (2005) ‘Guidelines for the use of intravenous immunoglobulin in neurological diseases’, The Association, London. 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, pp. 155-61. Available from: https://catalogue.nla.gov.au/Record/3808068. Federico P, Zochodne DW, Hahn AF et al (2000) ‘Multifocal motor neuropathy improved by IVIg: randomized, double-blind, placebo-controlled study’, Neurology, 55(9):1256–62, DOI: 10.1212/wnl.55.9.1256. 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. Gilhus NE, Barnes MR, Brainin M (2010) ‘European Handbook of Neurological Management’, 2nd Edition, Vol 1, Wiley-Blackwell, Oxford, pp. 343-50. Graham RC & Hughes RA (2006) ‘A Modified Peripheral Neuropathy Scale: The Overall Neuropathy Limitations Scale’, Journal of Neurology, Neurosurgery and Psychiatry, 77(8):973–976, DOI: 10.1136/jnnp.2005.081547. 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, 18(4):321-30, DOI: 10.1111/jns5.12046. 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, 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, 178:42–44. DOI: 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, 125(8):1875–86,DOI: 10.1093/brain/awf193. 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, 13(8):802–8, DOI: 10.1111/j.1468-1331.2006.01466.x. Van Schaik IN, van den Berg LH, de Haan R et al (2005) ‘Intravenous immunoglobulin for multifocal motor neuropathy’, Cochrane Database of Systematic Reviews, 2025(2):CD004429, DOI: 10.1002/14651858.CD004429.pub2. |