Combined inhibition of complement C5 and neonatal Fc receptor in refractory generalized myasthenia gravis: A report of two cases.

In patients with refractory generalized myasthenia gravis (MG) inadequately controlled by standard immunotherapies, including intravenous immunoglobulin and intravenous methylprednisolone, molecular targeted therapies have emerged as important treatment options. Although both neonatal Fc receptor (FcRn) inhibitors and complement C5 inhibitors have demonstrated efficacy in anti-acetylcholine receptor antibody-positive generalized MG, the clinical utility of their combined use remains unclear. Here, we report two cases of refractory anti-acetylcholine receptor antibody-positive generalized MG successfully managed with combined FcRn and C5 inhibition. In Case 1, disease control was not achieved despite thymectomy, multiple standard immunotherapies, and FcRn inhibition alone. Sequential treatment with C5 inhibitors, including eculizumab, ravulizumab, and zilucoplan, was attempted; sustained stabilization occurred only after combination therapy with zilucoplan and subcutaneous efgartigimod. In Case 2, standard therapies were ineffective, and thymectomy under general anesthesia was considered unsafe because of severe disease activity. Combination therapy was therefore introduced to stabilize the disease and enable safe perioperative management. Following successful thymectomy, targeted therapies were discontinued in Case 2, whereas Case 1 required ongoing treatment. To our knowledge, this is one of the first reports demonstrating effective disease control using combined FcRn and C5 inhibition in refractory generalized MG. These cases suggest that this strategy may benefit selected patients with refractory disease, particularly when stable disease control is required; however, further studies are warranted to determine its broader applicability and long-term safety.