Objective:

To compare the efficacy and safety of targeted therapies for generalized myasthenia gravis (gMG) using network meta-analysis.

Background:

Multiple targeted therapy classes exist for gMG, yet no head-to-head trials have been conducted. Indirect comparative evidence across clinician-rated and patient-reported outcomes is critically needed to guide treatment selection.

Design/Methods:

We systematically searched PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov through April 2026. Eligible studies were randomized placebo-controlled trials in adults with gMG reporting change from baseline in Quantitative Myasthenia Gravis (QMG) score, MG-Activities of Daily Living (MG-ADL) scale, overall adverse events (AEs), or serious adverse events (SAEs). Bayesian random-effects NMA with a half-normal prior on between-study heterogeneity was the primary analysis; frequentist NMA served as sensitivity. Drug-level and mechanistic class-level analyses were conducted. Treatment ranking used the Surface Under the Cumulative Ranking curve (SUCRA). 

Results:

Seventeen placebo-controlled RCTs encompassing 12 drugs across five mechanistic classes and 1,827 participants were included. For QMG, batoclimab ranked highest (SUCRA: 95.2%; MD: -5.37, 95% CrI: -8.06 to -2.92) but demonstrated no MG-ADL benefit (SUCRA: 24.7%; MD: 0.04, 95% CrI: -2.33 to 2.98), representing the most pronounced outcome-dependent rank reversal in the network. For MG-ADL, zilucoplan ranked first (SUCRA: 69.7%) and efgartigimod second (67.8%). At class level, complement inhibitors (MD: -1.92, 95% CrI: -2.82 to -1.04) and FcRN blockers (MD: -1.56, 95% CrI: -2.14 to -0.87) showed significant MG-ADL improvement. Satralizumab was the only agent with statistically confirmed excess overall AEs (OR: 3.21, 95% CI: 1.44-7.14). 

Conclusions:

No single targeted therapy demonstrates consistent superiority across clinician-rated and patient-reported outcomes in gMG. Batoclimab and efgartigimod show opposing rank reversals between QMG and MG-ADL, demonstrating that outcome selection critically determines comparative rankings. FcRN blockers and complement inhibitors provide the strongest class-level efficacy evidence. Satralizumab carries the only confirmed excess adverse event burden, underscoring the need for outcome-specific prescribing and head-to-head trials.