Real-world clinical effectiveness and exploratory longitudinal immunological changes of Efgartigimod in myasthenia gravis: a retrospective study and a single-cell analysis in one patient

Abstract

Efgartigimod, an antagonist of the neonatal Fc receptor, has demonstrated efficacy in generalized myasthenia gravis, but evidence from routine clinical practice remains limited, and its immunological effects beyond immunoglobulin G reduction are incompletely understood. We retrospectively evaluated the 12-week effectiveness and safety of Efgartigimod in 21 patients with acetylcholine receptor antibody-positive generalized myasthenia gravis. Outcomes included changes in Myasthenia Gravis Activities of Daily Living scores, response rates defined by reductions of ≥2 and ≥5 points, achievement of minimal symptom expression, changes in prednisone dosage, and adverse events. To explore potential longer-term immune changes, paired peripheral blood mononuclear cell samples obtained from one patient at baseline and after 6 months of repeated treatment were analyzed using single-cell RNA sequencing and T- and B-cell receptor repertoire sequencing. The median MG-ADL score decreased from 7.0 (IQR, 6.0–8.0) at baseline to 1.0 (IQR, 1.0–1.5) at week 12. After the first and second treatment cycles, 85.7 and 94.7% of patients achieved CMI, respectively, while 57.1 and 84.2% achieved ≥5-point reductions. At week 12, 73.7% of patients achieved MSE. Treatment was generally well tolerated, with two mild adverse events and no serious adverse events. Exploratory longitudinal profiling in one patient identified reduced myeloid inflammatory activity and antigen-presentation signatures, attenuated predicted inflammatory intercellular communication, and a more dispersed pattern of T- and B-cell clonal expansion after prolonged treatment. The clinical cohort findings support the effectiveness and favorable safety profile of Efgartigimod in routine practice. The exploratory single-cell and immune repertoire analyses from one patient provide preliminary insights into potential immunological changes beyond IgG reduction and require validation in larger cohorts.