Targeted Therapies in Generalized Myasthenia Gravis – A Narrative Review

Background Generalized myasthenia gravis (gMG) is a clinically and immunologically heterogeneous autoimmune disorder that can cause substantial functional impairment and life-threatening myasthenic crisis. Although symptomatic therapy and broad immunosuppression remain the basis of management, long-term treatment may be limited by incomplete disease control and treatment-related toxicity. Advances in understanding disease mechanisms have led to the development of therapies targeting specific immune pathways. Aim To summarize and critically evaluate the evidence on the efficacy and safety of existing and emerging targeted therapies for generalized myasthenia gravis. Materials and Methods A narrative review was conducted using PubMed, Google Scholar, and ClinicalTrials.gov, covering English-language sources from January 2016 to September 2026, with earlier landmark and mechanistic studies considered when relevant. A total of 87 sources were included. Evidence was grouped by therapeutic target and synthesized qualitatively, considering study design, autoantibody status, previous treatment exposure, and follow-up duration. Preliminary findings from conference abstracts and trial registries were distinguished from full peer-reviewed publications. Results FcRn and complement inhibitors improved clinical outcomes in several randomized trials, although study populations, endpoints, and treatment effects differed. Evidence for complement inhibition was concentrated in AChR-Ab-positive gMG; the primary endpoint of the pivotal eculizumab REGAIN trial did not reach statistical significance. Evidence for B-cell-directed therapies varied by agent and antibody subgroup. Support for rituximab in MuSK-Ab-positive disease came predominantly from observational studies, whereas inebilizumab demonstrated efficacy in a phase III trial involving AChR-Ab-positive and MuSK-Ab-positive patients. Findings for cytokine and intracellular signaling inhibitors were heterogeneous. CAR-T therapies showed preliminary clinical activity, but long-term safety and durability remained uncertain. Conclusions Targeted therapies have expanded treatment options for gMG, with the most extensive clinical evidence supporting FcRn and complement inhibition. The applicability of this evidence depends on autoantibody status, disease characteristics, previous treatment exposure, and agent-specific safety considerations. Differences between trials and limited direct comparisons prevent identification of an optimal treatment sequence. Further comparative and long-term studies are needed to clarify safety, sustained reductions in corticosteroid exposure, and the potential for durable treatment-free remission.