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. 2012 Dec 12;12(12):CD002277.
doi: 10.1002/14651858.CD002277.pub4.

Intravenous immunoglobulin for myasthenia gravis

Philippe Gajdos  1 , Sylvie Chevret, Klaus V Toyka
Affiliations

Intravenous immunoglobulin for myasthenia gravis

Philippe Gajdos et al. Cochrane Database Syst Rev. .

Abstract

Background: Myasthenia gravis is an autoimmune disease in which autoantibodies interfere with neuromuscular transmission. As with other autoimmune diseases, people with myasthenia gravis would be expected to benefit from intravenous immunoglobulin (IVIg). This is an update of a review first published in 2003 and last updated in 2007.

Objectives: To examine the efficacy of IVIg for treating exacerbations of myasthenia gravis or for chronic myasthenia gravis.

Search methods: We searched the Cochrane Neuromuscular Disease Group Specialized Register (11 October 2011), CENTRAL (2011, Issue 3), MEDLINE (January 1966 to September 2011) and EMBASE (January 1980 to September 2011) using 'myasthenia gravis' and 'intravenous immunoglobulin' as the search terms.

Selection criteria: All randomised controlled trials (RCTs) or quasi-RCTs in which IVIg was compared with no treatment, placebo or plasma exchange, in people with myasthenia gravis.

Data collection and analysis: One review author extracted the data and two others checked these data. For methodological reasons, no formal meta-analysis was performed.

Main results: We identified seven RCTs. These trials differ in inclusion criteria, comparison with alternative treatment and outcomes. In a trial comparing IVIg with placebo, including 51 participants with myasthenia gravis worsening, the mean difference (MD) in quantitative myasthenia gravis score (QMGS) (MD 95% CI) after 14 days was: -1.60 (95% CI - 3.23 to 0.03) this result being borderline statistically significant in favour of IVIg. In an unblinded study of 87 participants with exacerbation comparing IVIg and plasma exchange there was no difference in myasthenic muscle score (MMS) after 15 days (MD -1.00; 95% CI -7.72 to 5.72). In a study of 84 participants with worsening myasthenia gravis there was no difference in change in QMGS 14 days after IVIg or plasma exchange (MD -1.50; 95% CI -3.43 to 0.43). In a study of 12 participants with moderate or severe myasthenia gravis, which was at high risk of bias from skewed allocation, the mean fall in QMGS both for IVIg and plasma exchange after four weeks was significant (P < 0.05). A study with 15 participants with mild or moderate myasthenia gravis found no difference in change in QMGS 42 days after IVIg or placebo (MD 1.60; 95% CI -1.92 to 5.12). A study included 33 participants with moderate exacerbations of myasthenia gravis and showed no difference in change in QMGS 14 days after IVIg or methylprednisolone (MD -0.42; 95% CI -1.20 to 0.36). All these three smaller studies were underpowered. The last trial, including 168 people with exacerbations, showed no evidence of superiority of IVIg 2 g/kg over IVIg 1 g/kg on the change of MMS after 15 days (MD 3.84; 95% CI -0.98 to 8.66). Adverse events due to IVIg were moderate (fever, nausea, headache), self-limiting and subjectively less severe than with plasma exchange (although, given the available data, no statistical comparison was possible). Other than where specific limitations are mentioned the trials were generally at low risk of bias.

Authors' conclusions: In exacerbation of myasthenia gravis, one RCT of IVIg versus placebo showed some evidence of the efficacy of IVIg and two did not show a significant difference between IVIg and plasma exchange. Another showed no significant difference in efficacy between 1 g/kg and 2 g/kg of IVIg. A further, but underpowered, trial showed no significant difference between IVIg and oral methylprednisolone. In chronic myasthenia gravis, there is insufficient evidence from RCTs to determine whether IVIg is efficacious.

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Conflict of interest statement

One review author (PG) conducted two trials on IVIg supported by the Laboratoire Francais de Biotechnologie (LFB). This support consisted of the provision of IVIg but no other financial support. One review author (KVT) participated in the trial by Schuchardt 2002 (unpublished) as the chairman of the Advisory Board (receiving compensation of the equivalent of 500 Euros) and as a senior co‐author of the manuscript originally submitted but not published (no payments received). He participated in a conference of IgG treatments in chronic inflammatory neruopathy (receiving a payment of 3000 US$) and performed a research project on the neutralising role of IgG in animal models of inflammatory neuropathies and of Lambert‐Eaton myasthenic syndrome (public funding, no payments).

Figures

1
1
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 IVIg versus plasma exchange for exacerbation, Outcome 1 Change in MMS day 0 to 15.
2.1
2.1. Analysis
Comparison 2 IVIg versus methylprednisolone for MG exacerbation, Outcome 1 Change in QMGS day 0 to 14.
3.1
3.1. Analysis
Comparison 3 IVIg versus placebo, Outcome 1 Change in QMGS day 0 to 14.
3.2
3.2. Analysis
Comparison 3 IVIg versus placebo, Outcome 2 Change in QMGS day 0 to 28.
3.3
3.3. Analysis
Comparison 3 IVIg versus placebo, Outcome 3 Change in QMGS day 0 to 14 mild group.
3.4
3.4. Analysis
Comparison 3 IVIg versus placebo, Outcome 4 Change in QMGS day 0 to 28 mild group.
3.5
3.5. Analysis
Comparison 3 IVIg versus placebo, Outcome 5 Change in QMGS day 0 to 14 severe group.
3.6
3.6. Analysis
Comparison 3 IVIg versus placebo, Outcome 6 Change in QMGS day 0 to 28 severe group.
4.1
4.1. Analysis
Comparison 4 IVIg 1g/kg versus IVIg 2g/kg, Outcome 1 Change in MMS day 0 to 15.
5.1
5.1. Analysis
Comparison 5 IVIg versus plasma exchange for worsening MG, Outcome 1 Change in QMGS day 0 to day 14.
5.2
5.2. Analysis
Comparison 5 IVIg versus plasma exchange for worsening MG, Outcome 2 Change in QMGS day 0 to day 21.
5.3
5.3. Analysis
Comparison 5 IVIg versus plasma exchange for worsening MG, Outcome 3 Change in QMGS day 0 to day 28.
6.1
6.1. Analysis
Comparison 6 IVIg versus placebo for severe stable MG, Outcome 1 Change in QMGS day 0 to 42.
6.2
6.2. Analysis
Comparison 6 IVIg versus placebo for severe stable MG, Outcome 2 Change in MG‐ADL day 0 to 42.
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References

References to studies included in this review

Barth 2011 {published data only}
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