Differential response to ofatumumab in anti-AChR and anti-MuSK positive myasthenia gravis patients: a single-center retrospective study

Background: Ofatumumab (OFA), a humanized anti-CD20 monoclonal antibody, shows potential in myasthenia gravis (MG) with antibody against acetylcholine receptor (AChR-Ab), but comparative efficacy across AChR and muscle-specific kinase (MuSK) subtypes remains uncharacterized. Objectives: To evaluate OFA’s clinical and immunological effects in AChR-MG versus MuSK-MG, identify predictors of minimal symptom expression (MSE), and explore the dynamics of B-cell repopulation. Design: A retrospective study in a single center. Methods: Twenty-one refractory MG patients (13 MuSK+, 8 AChR+) received individualized OFA induction (Regimen 1: two 20 mg doses ⩾2 weeks apart; Regimen 2: single 20 mg dose) and maintenance (20 mg upon CD19 + B counts ⩾5 cells/μL repopulation or clinical exacerbation). Outcomes included time-to-MSE, Quantitative Myasthenia Gravis Score (QMGS) dynamics, prednisone reduction, and serial immunophenotyping (B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), soluble CD40L (sCD40L), microphage migration inhibitory factor (MIF), and immunoglobulin). Results: MuSK-MG achieved faster MSE (median time: 6 vs 15 months, log-rank p = 0.164, age-adjusted Cox p = 0.027), and a higher 3-month improvement (92.3% vs 50.0%; p = 0.047). Earlier achievement of MSE was associated with shorter disease duration ( p = 0.038) and concomitant corticosteroid therapy ( p = 0.030). Prednisone doses decreased significantly over 6 months ( p = 0.029) without difference between groups ( p = 0.109). MuSK-MG showed synchronized BAFF/APRIL declines while AChR-MG presents transient BAFF elevation and sustained APRIL. BAFF levels showed a significant positive correlation with QMGS in MuSK-MG, while IgM/IgG positively correlated with QMGS in both subtypes. Median B cell-repopulation time was 47.7 days. Conclusion: OFA demonstrates superior efficacy in MuSK-MG with distinct immunological modulation. AChR-MG requires combinatorial strategies targeting compensatory pathways.