C5 complement inhibition versus FcRn modulation in generalised myasthenia gravis.

Area of Science:

• Neurology
• Immunology
• Pharmacology

Background:

• Myasthenia gravis (MG) is an autoimmune neuromuscular junction disorder causing fluctuating muscle weakness.
• Standard immunosuppression is insufficient for a significant subgroup of MG patients.
• Complement factor C5 inhibition (C5IT) and neonatal Fc receptor (FcRn) antagonism are emerging therapies with limited comparative real-world data.

Purpose of the Study:

• To compare the real-world effectiveness and safety of C5IT and FcRn antagonists in myasthenia gravis (MG) patients.
• To provide crucial comparative data for guiding treatment decisions in refractory MG.
• To evaluate clinical outcomes and safety profiles within the first six months of treatment initiation.

Main Methods:

• Retrospective analysis of 153 MG patients from 8 German centers.
• Patients received either C5IT (eculizumab, ravulizumab) or efgartigimod (FcRn antagonist).
• Propensity score matching (PSM) was used to compare outcomes and safety profiles.

Main Results:

• Both C5IT and FcRn antagonists demonstrated rapid clinical improvements and reduced prednisolone doses.
• Insufficient response rates varied (20%-49.1%) based on MG-specific scores.
• After PSM, comparable reductions in MG-Activities of Daily Living (MG-ADL) scores were observed in both groups, with similar secondary outcome results.

Conclusions:

• Real-world data indicate comparable efficacy and safety between C5IT and FcRn antagonism in myasthenia gravis (MG).
• These findings contrast with some meta-analyses and indirect comparisons of clinical trial data.
• The study provides valuable evidence for clinical decision-making in managing refractory MG patients.