Multifocal Motor Neuropathy With Conduction Blocks Medication

Updated: Nov 12, 2018
  • Author: Sasa Zivkovic, MD, PhD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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Medication

Medication Summary

Multifocal motor neuropathy (MMN) is an immune-mediated disorder, and while multiple immunomodulatory and immunosuppressive treatments have been used, only intravenous immunoglobulin (IVIG), [21, 22, 23] subcutaneous immunoglobulin (SCIG) [24, 25] and cyclophosphamide have been consistently effective. Delay of treatment may result in increased weakness and disability. Anecdotal reports also indicate that rituximab, [26, 27, 28] interferon-beta, azathioprine and cyclosporine may be efficacious. [29, 30]

The presence of conduction blocks or elevated titers of anti-GM1 antibodies are not reliable predictors of response to treatment with IVIG.

Most patients (~80-90%) improve with IVIG, but frequently long-term maintenance IVIG infusions are required to prevent worsening of symptoms. [23, 31] The pharmacokinetics of IVIG vary among individual patients and may influence the clinical response. [32] Subcutaneous immunoglobulin (SCIG) infusions may be used as an alternative to IVIG with similar efficacy and improved safety profile. [33]

Cyclophosphamide may be used in combination with plasmapheresis. Lack of benefit was reported for 1 patient who received high-dose cyclophosphamide treatment followed by autologous stem cell transplantation. [34]

Corticosteroids or plasmapheresis (without cyclophosphamide) is not effective, and in some cases, MMN may even worsen. Mycophenolate is ineffective as adjunct treatment with IVIG. [31]

Recent reports describe effective treatment with cyclosporine and rituximab in a small number of patients, but additional data are needed before these would be recommended for treatment of MMN.

Other treatments used with variable success include interferon-beta and azathioprine.

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Immune Globulin

Class Summary

IVIG infusions are the mainstay of MMN treatment. Patients are initially treated with IVIG (2 g/kg) over 2-5 days, followed by maintenance infusions. The frequency of maintenance treatments depends on patients' symptoms, and it is usually every 4-8 weeks. Maintenance dose is determined by patient's response and typically ranges from 1-2 g/kg per treatment. Infusions are performed in an inpatient setting (hospital), in outpatient settings (infusion center or physician's office), or at home. Most patients improve with IVIG treatments (~80-90%), and dosing must be individualized based on patient's response.

Subcutaneous immunoglobulin (SCIG) therapy is used as an alternative to IVIG and can provide more treatment flexibility and autonomy for the patients. Infusion-related adverse effects are less common with SCIG than with IVIG, and SCIG may be given at home by the patient and his or her family. SCIG does require more frequent dosing (typically weekly). The optimal dosing of SCIG has not been established and various ratios of IVIG to SCIG have been used from 1:1 to 1:1.53, and others. [24]

Long-term IVIG treatment improves muscle strength and functional disability, but the responsiveness may decrease over time.

If IVIG is not (sufficiently) effective, then alternative treatments (eg, cyclophosphamide, rituximab, cyclosporin) should be considered.

Immunoglobulin, intravenous (Gamimune, Gammar-P, Sandoglobulin, Gammagard Liquid and S/D, Gammunex, Carimune, Flebogamma, Gamaplex, Octigam, Privigen)

Intravenous immunoglobulin neutralizes circulating myelin antibodies through anti-idiotypic antibodies. It down-regulates proinflammatory cytokines, including INF-gamma. It blocks Fc receptors on macrophages, suppresses inducer T and B cells and augments suppressor T cells, blocks complement cascade, and promotes remyelination. It may increase CSF IgG (10%).

After 3-7 years of treatment, IVIG may become less effective, possibly because of development of axonal degeneration.

In other patients, few doses of IVIG may induce prolonged remission.

Immune globulin, subcutaneous (Hizentra, Gammagard Liquid, and Gamunex-C )

Immune globulin subcutaneous is used to treat patients with primary immune deficiency. It has also been used in the treatment of autoimmune neuromuscular disorders. It supplies a wide spectrum of IgG antibodies against bacteria, viral, mycoplasma, and parasitic agents, as well as their antigenic toxins. It is also used in patients with poor venous access and those who want to be able to self-administer to increase independence in administration.

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Immunomodulators

Class Summary

These agents are used to modify the activity of the immune system.

Rituximab (Rituxan)

Rituximab is a second-line agent that may be used for patients with MMN who do not respond to IVIG. Its efficacy is based on anecdotal reports. While most patients exhibiting a response to rituximab had positive anti-GM1 IgM antibodies, improvement was observed in seronegative patients as well.

Rituximab is a genetically engineered chimeric murine/human monoclonal antibody directed against CD20 antigen found on the surface of normal and malignant B lymphocytes. The antibody is an IgG1 kappa immunoglobulin containing murine light- and heavy-chain variable region sequences and human constant region sequences.

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Immunosuppressive Agents

Class Summary

Cyclophosphamide is primarily used in patients with severe symptoms that do not respond to IVIG infusions and may be combined with plasmapheresis. Use of cyclophosphamide induced remission in 50-80% patients, but it is not routinely administered because of potential adverse effects. Oral cyclophosphamide is not as effective as intravenous therapy, and has the potential for more frequent dose-limiting adverse effects, so intravenous infusions are preferred.

The use of cyclophosphamide should be limited to more severely affected patients given the potential adverse effects.

Cyclophosphamide (Cytoxan)

Cyclophosphamide is chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells.

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