Efgartigimod for generalized myasthenia gravis: a comprehensive review of clinical evidence and future perspectives.

Efgartigimod, a first-in-class neonatal Fc receptor (FcRn) antagonist, has transformed the therapeutic landscape of generalized myasthenia gravis (gMG). This review synthesizes evidence from pivotal trials to real-world applications. The phase 3 ADAPT trial demonstrated rapid, clinically meaningful improvements in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores in anti-acetylcholine receptor antibody-positive (AChR-Ab+) patients, with a favorable safety profile. Long-term extension studies confirmed reproducible efficacy and sustained safety across multiple treatment cycles. Subsequent research optimized dosing through flexible, individualized regimens and a subcutaneous formulation, enhancing patient convenience. Extensive real-world evidence validates these findings across diverse populations, including antibody-negative patients, those with acute exacerbations or myasthenic crisis, and thymoma-associated MG, consistently showing rapid response and steroid-sparing effects. When real-world evidence is stratified by antibody status, thymic pathology, and age at onset, efgartigimod shows consistent benefits across most subgroups, including MuSK-positive and seronegative patients. Emerging data suggest immunomodulatory effects beyond IgG reduction, influencing B-cell populations and gene expression profiles. While comparative efficacy against other novel biologics (complement inhibitors, other FcRn antagonists) remains under investigation through indirect analyses, efgartigimod's rapid onset, cyclical administration allowing drug holidays, and broad applicability distinguish it. Distinct biomarker profiles are emerging for FcRn blockade versus complement inhibition, with the former linked to measurable changes in IgG subclasses and immune cell phenotypes. Ongoing research focuses on optimizing patient selection, exploring combination therapies, and expanding applications to other IgG-mediated autoimmune diseases. Efgartigimod represents a cornerstone of targeted immunotherapy in MG, offering personalized, effective, and well-tolerated disease management.