Double‐Filtration Plasmapheresis Versus Efgartigimod for Generalized Myasthenia Gravis: Severity‐Stratified Benefits in a Prospective Observational Multicenter Study

ABSTRACT Introduction Double‐Filtration plasmapheresis (DFPP) and efgartigimod (EFG) are both effective acute exacerbation therapies for generalized myasthenia gravis (gMG), yet real‐world comparative evidence remains limited. This study aims to systematically compare their clinical efficacy and safety to guide individualized treatment strategies. Methods This prospective multicenter study (Aug 2019–Mar 2025) evaluated gMG patients treated with a cycle of DFPP (3–5 sessions) or EFG (4 weekly infusions). Primary endpoints included changes in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Activities of Daily Living (MG‐ADL) scores from baseline (T0) to post‐treatment (T1) and 1 month after T1 (T2). Secondary endpoints covered clinical meaningful improvement (CMI), deep improvement rates (defined as ≥ 5‐point reduction in MG‐ADL or ≥ 9‐point in QMG), immunological changes, and safety. Results Among 66 MG patients (EFG = 41, DFPP = 25), both DFPP and EFG significantly reduced QMG and MG‐ADL scores at T1 and T2. In moderate‐to‐severe gMG (MGFA ≥ IIb), 3/5‐session DFPP was superior to 4‐infusion EFG at T2 ( p < 0.05), while efficacy was comparable in mild cases (MGFA ≤ IIa). Sustained CMI rates (through T2) increased with higher treatment intensity; the 5‐session DFPP rate was significantly higher than the 3‐session DFPP (85% vs. 45%, p = 0.049) and numerically higher than the 4‐infusion EFG (85% vs. 70%, p = 0.413). The proportion of patients achieving deep improvement in 5‐session DFPP was higher than 4‐infusion EFG. DFPP broadly reduced immunoglobulins/complement versus EFG's selective immunoglobulin G (IgG) reduction. Adverse events occurred in 28.0% of the DFPP group (mainly catheter‐related thrombosis) and 39.0% of the EFG group (predominantly headache; p = 0.431), with no serious events reported. Conclusion Both DFPP and EFG effectively treat gMG, though DFPP offers greater benefit in moderate‐to‐severe cases, underscoring the need for individualized therapy.