C5 complement inhibition versus FcRn modulation in generalised myasthenia gravis

Background Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions, leading to fluctuating muscle weakness. While many patients respond well to standard immunosuppression, a substantial subgroup faces ongoing disease activity. Emerging treatments such as complement factor C5 inhibition (C5IT) and neonatal Fc receptor (FcRn) antagonism hold promise for these patients. However, the current landscape is hindered by a paucity of comparative data that is crucial for treatment decisions.Objective This study aims to compare the effectiveness and safety of C5IT and FcRn antagonists in a real-world setting.Methods A retrospective analysis of 153 MG patients from 8 German specialised MG centres receiving either C5IT (26 eculizumab, 80 ravulizumab) or efgartigimod (47 patients) was conducted. Propensity score matching (PSM) was employed to compare changes in MG-specific outcome parameters within the first 6 months after treatment initiation, along with safety profiles and concomitant MG therapy.Results Both treatment strategies led to rapid clinical improvements and substantial reductions in prednisolone doses. However, insufficient response was noted in 20%-49.1% of patients based on Quantitative MG and MG Activities of Daily Living (MG-ADL) scores. We did not identify any new safety concerns. After PSM, 40 patients remained in each group. In both cohorts, reductions in MG-ADL as prespecified primary study endpoint were comparable. Moreover, analyses of secondary outcome parameters demonstrated similar results for C5IT versus FcRn.Conclusion In contrast to current meta-analyses and indirect comparisons of clinical trial data, our real-world study demonstrates comparable efficacy and safety of C5IT and FcRn antagonism in MG.