Plasma Exchange versus Intravenous Immunoglobulin in Worsening Myasthenia Gravis: A Systematic Review and Meta-Analysis with Special Attention to Faster Relapse Control

Abstract

Currently used rescue interventions to prevent rapid myasthenic deterioration are plasma exchange (PLEX) and intravenous immunoglobulin (IVIG). We investigated the evidence to determine whether the two methods were interchangeable or whether one was superior to the other. This review was registered on PROSPERO (CRD42021285985). Only randomized controlled trials (RCTs) comparing the efficacy and safety of PLEX and IVIG in patients with moderate-to-severe myasthenia gravis (MG) were included. Five major databases were systematically searched (PubMed, CENTRAL, Embase, Scopus, and Web of Science). Odds ratios (OR) with 95% confidence intervals (CI) were calculated for adverse events and mean differences (MD) for changes in quantitative myasthenia gravis scores (QMG). Three RCTs met the inclusion criteria. Two investigating 114 patients in total were eligible for meta-analysis to analyze efficacy and safety. For the change in QMG score, the MD was -2.8 (95% CI: -5.614-0.113), with PLEX performing better. For adverse events, an OR of 1.04 was found (95% CI: 0.25-4.27). This study demonstrated a low risk of bias in evaluating treatment efficacy but indicated a high risk of bias in assessing procedural safety outcomes. Although the results did not show any significant difference, there was a tendency indicating faster efficacy of PLEX in the first two weeks of treatment. In such a critical clinical condition, this tendency may be clinically meaningful, but further studies should clarify this benefit.

Keywords: intravenous immunoglobulin; meta-analysis; myasthenia gravis; plasma exchange; relapse.

Figure 1

It explains the PICO criteria for the meta-analysis. This figure illustrates the studied population, the intervention, and the comparator, as well as presenting the outcomes. In our study, adult patients with moderate or severe myasthenia gravis were investigated in the adult population.

Figure 2

Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA 2020) flow diagrams are shown in the Figure. Due to the rigorous criteria only two studies could be included in the meta-analysis. The rest of the studies had to be excluded as the examined parameters did not sufficiently overlap (e.g., studies examining the overall effect of thymectomy, or using scoring systems other than QMG).

Figure 3

Meta-analysis results comparing the effectiveness of PLEX and IVIG in severe to moderate MG patients were measured by QMG [38,39]. Within the examined timeframe of two weeks, PLEX might show better efficacy in patients with deteriorating myasthenic symptoms, although the difference may have missed the level of significance. In the case of rapidly worsening myasthenic symptoms, this difference deserves attention by clinicians; nevertheless, its confirmation requires further clinical studies. This tendency is also demonstrated by the Common Effects vs. Random Effects model comparison.

Figure 4

Meta-analysis results comparing the number of adverse events within 30 days between PLEX and IVIG treatments in severe to moderate MG [38,39]. The graph clearly shows no major difference in the overall AE occurrence between the two interventions. It is important to note that the results had a high risk of bias (see Table 2).