Regimen-stratified Bayesian model-based meta-analysis of targeted biologics in generalised myasthenia gravis: efficacy comparison, mechanism-level class contrast, and endpoint sensitivity with model-informed trial design
Abstract
Nine targeted biologics spanning four mechanisms have reached phase III development for generalised myasthenia gravis, yet no cross-programme comparison accounts for the distinct continuous versus cyclical dosing patterns or integrates both patient-reported (MG-ADL) and clinician-assessed (QMG) scales. We performed a regimen-stratified Bayesian model-based meta-analysis (MBMA) to compare efficacy, evaluate mechanism-level class differences, and inform trial design. Longitudinal MG-ADL and QMG data were extracted from nine placebo-controlled phase III trials. Six hierarchical nonlinear Emax models were fitted with inverse-variance weighting. Drug-specific maximum efficacy, net benefit over placebo, week 26 predictions, time to the minimum clinically important difference (MCID), cumulative efficacy, ranking probabilities, and mechanism-level class contrasts were derived. Robustness was assessed via model comparison, prior sensitivity, and Leave-one-study-out analyses on both scales. Endpoint-sensitivity simulation and a treatment-selection framework were appended. The study was registered with PROSPERO: CRD420261288549. On MG-ADL, zilucoplan led with the highest Emax (4.8 points; 95% CrI: 4.2-5.4) and largest net benefit (2.5; 2.0-3.1). On QMG, batoclimab led (Emax 5.9; 4.4-9.5; net benefit 4.1; 2.7-7.7). Efgartigimod achieved the fastest onset on both scales (≤ 1.6 weeks). At the mechanism class level, neonatal Fc receptor (FcRn) inhibitors demonstrated decisive superiority…
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