Comparison of the Efficacy and Safety of Myasthenia Gravis Treatments: A Bayesian Network Meta-Analysis.

Abstract

In the past decade, several novel therapies have shown promise in treating generalized myasthenia gravis (MG); however, no head-to-head prospective studies have compared their efficacy and safety. To assist clinicians in navigating this complex treatment landscape, we sought to compare treatments while accounting for differences in trial populations. We conducted a Bayesian network meta-analysis (PROSPERO ID: CRD42023428733) of MG treatments. We searched Scopus, Embase, Web of Science, CENTRAL, and MEDLINE up to May 2, 2025, for randomized trials in MG. Two independent reviewers (N.M. and M.R.) identified prospective multiarm studies of adults (18 or older) with generalized MG that reported mean treatment difference, with uncertainty, in MG-Activities of Daily Living (MG-ADL) or Quantitative MG (QMG) score change from baseline. Of 4,823 eligible studies, 27 placebo-controlled randomized trials (placebo n = 1,086; treatment n = 1,232) were included that targeted B cells, neonatal Fc receptor (FcRn), complement activity, CD40, and interleukin-6 signaling, as well as immunoglobulin G and broad immunosuppression therapy. Compared to those treated with placebo and standard of care, QMG scores decreased by an average of -3.63 (95% credible interval -4.43 to -2.77) points more in patients treated with FcRn inhibitors, -2.59 (-3.92 to -1.28) points more in patients treated with C5 complement inhibitors (C5i), and -2.50 (-5.11 to 0.12) points more in patients treated with CD19⁺ B-cell depletion therapy (BCDT). The MG-ADL treatment effects were -1.93 (-2.21 to -1.65) for FcRn inhibitors, -1.84 (-2.48 to -1.19) for C5i, and -1.91 (-2.97 to -0.84) for CD19⁺ BCDT. Sensitivity analyses detected potential confounding of treatment effects by age and sex. Patients treated with FcRn inhibitors had greater odds of treatment-related adverse events (odds ratio 2.20 [1.52-3.38]) compared with the placebo group, while C5i and CD19⁺ BCDT showed odds comparable to placebo. FcRn inhibitors, C5i, and CD19⁺ BCDT showed comparable efficacy in terms of QMG and MG-ADL reduction because meaningful differences were not observed between treatment classes. Our findings also highlight how differences between trial populations may confound the interpretation of study outcomes. Prospective comparative efficacy studies are warranted.