A 2023 international guideline reviewed the role of intravenous immunoglobulin (IVIG) in the management of myasthenia gravis, including its use in acute exacerbations and myasthenic crisis. The guideline synthesized evidence from randomized trials, comparative studies, and expert consensus evaluating IVIG dosing strategies and clinical outcomes. Standard IVIG regimens for acute exacerbation were identified as 0.4 g/kg/day for 5 consecutive days or 1 g/kg/day for 2 days, corresponding to a total cumulative dose of 2 g/kg. Outcomes assessed included improvement in quantitative myasthenia gravis (QMG) scores, duration of myasthenic crisis, ventilatory requirements, and clinical stabilization, with IVIG demonstrating efficacy comparable to plasmapheresis in moderate to severe disease. The authors noted that in selected cases, lower cumulative doses (e.g., 1 g/kg total) may be sufficient, while IVIG has also been used off-label as maintenance therapy in specific clinical scenarios; however, no randomized or controlled data were identified supporting cumulative doses exceeding 2 g/kg. Based on the available evidence, the guideline concludes that IVIG doses up to 2 g/kg are supported for MG exacerbation and crisis, and there is no evidence within the reviewed literature to support dosing up to 4 g/kg, regardless of administration over 2-5 days. [1]
A 2022 review evaluated the immunomodulatory mechanisms and clinical use of IVIG in myasthenia gravis (MG), with a focus on its role in acute exacerbations and factors influencing treatment response. The review summarized clinical trial data demonstrating that IVIG administered at a total dose of 2 g/kg, typically divided over 2 consecutive days, produces clinically meaningful improvements in disease severity scores within days in patients with severe MG exacerbations. While no controlled clinical trials were identified that directly evaluated IVIG doses up to 4 g/kg for MG exacerbations, the authors discussed pharmacogenomic data indicating that polymorphisms in the neonatal Fc receptor (FcRn) receptor gene (VNTR2/3 genotype) are associated with increased IgG catabolism and reduced IVIG exposure. Based on these mechanistic and pharmacokinetic considerations, the authors noted that some patients with MG who respond inadequately to standard dosing are likely to require higher IVIg doses (such as super-high IVIg at 3-4 g/kg per month) or more frequent administrations if 2 g/kg is not effective. The authors concluded that while 2 g/kg remains the evidence-supported standard for acute MG exacerbations, higher cumulative doses may be biologically plausible in refractory patients, though this strategy is based on expert opinion and indirect evidence rather than direct clinical trial data and warrants further study. [2]
A 2012 review evaluated randomized controlled trials assessing the efficacy and dosing of IVIG for MG exacerbation, worsening disease, and chronic stable disease. The review included seven RCTs comparing IVIG with placebo, plasma exchange, corticosteroids, or alternative IVIG dosing regimens, with outcomes primarily assessing changes in myasthenic muscle score (MMS) and QMG score within 7-15 days of treatment. Standard IVIG dosing across trials ranged from 1 g/kg total to 2 g/kg total, administered either as 0.4 g/kg/day over 3-5 days or 1 g/kg/day over 1-2 days. Importantly, the largest dose-comparison trial (N= 168) demonstrated no statistically significant superiority of 2 g/kg over 1 g/kg in clinical improvement, and the authors concluded that any potential benefit of higher dosing was small and not clinically meaningful. No trials evaluated cumulative IVIG doses exceeding 2 g/kg, and there is no evidence in this review to support IVIG dosing up to 4 g/kg for myasthenia gravis exacerbation or worsening. [3]
A 2023 review evaluated randomized controlled trials comparing IVIG and plasma exchange (PLEX) for the treatment of moderate-to-severe worsening myasthenia gravis, focusing on efficacy, safety, and speed of relapse control. Across the included trials, IVIG dosing regimens varied but were limited to conventional cumulative doses, including 2 g/kg administered as 1 g/kg/day over 2 days or 0.4 g/kg/day over 5 days, with no studies evaluating IVIG doses exceeding 2 g/kg per treatment course. The meta-analysis of 114 patients demonstrated no statistically significant difference in overall efficacy between IVIG and PLEX based on changes in QMG scores, although there was a nonsignificant trend toward faster improvement with PLEX within the first two weeks. Safety outcomes showed no significant difference in adverse event rates between IVIG and PLEX, though adverse event reporting carried a high risk of bias. Importantly, the authors highlighted heterogeneity in IVIG dosing across trials and emphasized that existing randomized evidence in MG relapse is confined to standard dosing strategies, providing no direct clinical data to support IVIG doses up to 4 g/kg for myasthenia gravis exacerbations. [4]