Targeted Therapies in Generalized Myasthenia Gravis: An Umbrella Review of Evidence Quality and Overlap

Generalized myasthenia gravis (gMG) is an antibody-mediated autoimmune disorder in which complement C5 inhibitors and neonatal Fc receptor (FcRn) antagonists have expanded therapeutic options, while rituximab remains used off-label in selected patients. We conducted an umbrella review to critically appraise systematic reviews and evidence syntheses evaluating complement inhibitors and/or FcRn antagonists within a therapeutic framework that also included rituximab. MEDLINE/PubMed, Embase, Epistemonikos, Google Scholar, and supplementary citation sources were searched from 2015 onward, with an updated search on 15 August 2026. Methodological quality was assessed with AMSTAR 2 and primary-study overlap with the corrected covered area (CCA) and GROOVE. Ten reviews/evidence syntheses met eligibility criteria. Complement inhibitors and FcRn antagonists were generally associated with improvements in MG-ADL and QMG, although estimates and rankings varied. AMSTAR 2 rated one review as high confidence, four as low confidence, and five as critically low confidence. Primary-study overlap was very high (CCA 32.59%), with 36 of 45 pairwise comparisons classified as very high. Comparative evidence, including rituximab, was predominantly indirect. Targeted therapies provide clinically relevant benefit. The protocol was registered with the Open Science Framework (OSF, 27 June 2025).