Abstract: 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. 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.

Plain-language summary: Five of the RCTs evaluated the efficacy of IVIg for the treatment of exacerbations or worsening (the former being usually more severe than the latter). One RCT of IVIg versus placebo, which included 51 participants, showed some evidence of the efficacy of IVIg for treating myasthenia gravis with worsening weakness. Two trials, the first of which included the first 87 and the second 84 participants, showed no significant difference between IVIg and plasma exchange. In the first of these trials there was a high risk of bias because the assigned treatments were not hidden. A trial including 33 participants showed no difference in efficacy between IVIg and a corticosteroid (methylprednisolone) but did not recruit enough participants to detect an effect, so there is insufficient evidence to favour IVIg over corticosteroids in moderate exacerbations. Another trial, which included 168 participants, showed no evidence of superiority of IVIg 2 g/kg over IVIg 1 g/kg on the change of myasthenic muscle score (MMS) after 15 days (MD 3.84; 95% CI -0.98 to 8.66). Two RCTs evaluated the efficacy of IVIg for the treatment of moderate or severe myasthenia gravis. One compared, in 12 participants, IVIg and plasma exchange. The second, with 15 participants included, compared IVIg and a placebo. Both are underpowered and the first at some risk of bias, so no conclusion could be drawn from these two trials. There is no evidence from RCTs nor from other trials to determine whether IVIg improves function or reduces the need for steroids.