Comparing the Safety and Efficacy of Myasthenia Gravis Treatments: A Bayesian Network Meta-analysis Accounting for Inconsistencies in Trial Designs and Populations
Bhaskar Roy1, Nilay McLaren2, Wayne Zhong2, Sheena Hussain3, Richard Nowak4
1Neurology, Yale University, 2Neurology, Yale School of Medicine, 3Kolkata Medical College, 4Yale University School of Medicine
Objective:
We compared the efficacy and safety of myasthenia gravis (MG) treatments leveraging a Bayesian hierarchical model accounting for the inconsistencies in trial designs and populations.
Background:
In the last decade, many novel targeted therapies have shown promise in treating generalized MG; however, no head-to-head prospective studies have compared efficacy and safety between one another, nor to existing therapies. As a viable alternative, we conducted a Bayesian network meta-analysis, designed to account for inconsistencies in study designs and populations.
Design/Methods:
Twenty-seven trials (publication date range: 1987-2025; placebo n=1,086; treatment n=1,232) reporting change from baseline in MG-Activities of Daily Living (MG-ADL) or Quantitative MG (QMG) score, targeting B-Cells, neonatal Fc receptor (FcRn), complement activity, CD40, Interleukin-6 signaling, immunoglobulin G, and broadscale immunosuppression were included.
Results:
QMG scores decreased by an average of -3.6 (95% Credible Interval: [-4.40, -2.72]) points more in patients treated with FcRn inhibitors than those treated with placebo/standard of care, followed by -2.59 [-3.93, -1.27] points for C5 complement inhibitors, and -2.50 [-5.15, 0.13] points for CD19 Depletion. MG-ADL scores decreased by -1.94 [-2.23, -1.67] in patients treated with FcRn inhibitors, -1.89 [-2.95, -0.83] for CD19 Depletion, and -1.78 [-2.43, -1.13] for C5 complement inhibitors. These results remained consistent in sensitivity analyses. In simulations, FcRn inhibitors had a probability of 0.873 of having the greatest QMG treatment effect and 0.834 for MG-ADL. Patients treated with FcRn inhibitors had greater odds of treatment-related adverse events (Odds Ratio: 2.20 [1.52, 3.38]) while C5 complement inhibitors and CD19 depletion showed comparable odds to placebo/standard of care.
Conclusions:
This meta-analysis cannot substitute randomized trials, but compares the benefits and adverse events of targeted therapies and will help make evidence-based therapeutic choices in MG.
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