Kei Ishizuchi

Thymoma‐associated myasthenia gravis (TAMG) is frequently refractory, particularly when complicated by myasthenic crisis in advanced invasive disease. Complement C5 inhibitors and neonatal Fc receptor (FcRn) inhibitors have expanded the treatment of acetylcholine receptor (AChR) antibody‐positive generalized myasthenia gravis; however, their optimal selection, sequencing, and combined use in refractory TAMG remain undefined. We report a case of a 46‐year‐old man with Masaoka–Koga stage IVa invasive thymoma and pleural dissemination who developed a prolonged ventilator‐dependent myasthenic crisis after debulking surgery. Immunoadsorption plasmapheresis, intravenous immunoglobulin, and ravulizumab produced only transient benefit. Serum complement activity became undetectable after ravulizumab was switched to zilucoplan (a peptide C5 inhibitor chosen because it is not affected by FcRn blockade), yet sustained respiratory stability was not achieved. Only after subcutaneous efgartigimod was added to ongoing zilucoplan did the patient attain sustained daytime ventilator independence, with a parallel decline in anti‐AChR antibody titer and total immunoglobulin G. He was discharged and remained clinically stable, with no worsening during a subsequent mild infection. Reviewing this case together with previously reported patients who received concurrent or sequentially overlapping C5 and FcRn inhibition, we discuss the biological rationale for dual‐pathway targeting, pharmacological considerations relevant to agent selection and sequencing, and infectious‐safety implications. This temporal association does not establish efficacy; however, combined C5 and FcRn inhibition may be considered, on an individualized basis, in selected refractory TAMG cases when single‐pathway therapy is insufficient.

Efgartigimod, which has been well tolerated and efficacious in individuals with generalized myasthenia gravis (MG), is available in Japan not only for the treatment of anti–acetylcholine receptor–positive (AChR+) but also anti–muscle-specific receptor tyrosine kinase (MuSK+) and seronegative generalized MG. We report details of the use of efgartigimod for generalized MG in clinical practice in Japan. We included patients with generalized MG in the 2021 survey of Japan Myasthenia Gravis Registry (JAMG-R) study group who received an initial cycle of efgartigimod between May and September 2022. We defined “responders” as patients who achieved a score ≥2 points for MG activities of daily living (MG-ADL) in the first treatment cycle. The MG composite and the Revised scale of the 15-item Myasthenia Gravis–Quality of Life scale (MG-QOL15-r) were also evaluated. Of 1,343 JAMG-R patients, 36 (2.7%) started efgartigimod (female 68%, age 53 years). Their serologic profiles were as follows: AChR+, n = 19 (53%); MuSK+, n = 6 (17%); and seronegative, n = 11 (31%). Twenty-six patients (72%) had refractory MG. There were 81 cycles of efgartigimod during the 26-week observation in 34 patients (average, 2.4 cycles). The mean interval between cycles was 5.9 weeks. A continuous 4-weekly infusion of efgartigimod was performed in 65 (80%) of 81 cycles. In the first cycle, the MG-ADL score of the 34 patients decreased significantly from 10.5 ± 4.3 to 6.9 ± 5.1 (p = 0.003). Similarly, the mean MG composite and MG-QOL15-r decreased from 18.4 ± 13.6 to 11.8 ± 9.6 (p = 0.004) and from 19.2 ± 6.3 to 14.2 ± 8.3 (p = 0.007), respectively. Twenty-one (62%) patients were responders. Therapeutic responses were observed in the subsequent cycles. The duration of effectiveness of efgartigimod was varied among the responders; 4 responders had only a single effective cycle. Significant improvement was observed in the MuSK+ patients. Prednisolone dose of 7 patients was reduced. Our examination of the patients' postintervention status revealed that 6 patients achieved minimal manifestations. COVID-19 occurred in 5 patients. We failed to detect clinical or laboratory findings associated with responders. Efgartigimod can be considered for the treatment of patients with generalized MG who do not achieve minimal manifestations, with a broad flexibility of patient selection and treatment schedules.

症例は50代女性で，2か月前より持続する右上眼瞼周囲の頭痛のため受診となった．頭部MRI T₂強調画像で脳梁，両側放線冠に多発性の高信号病変を認めた．自己免疫疾患を考えステロイドパルス療法を施行したが，右眼に下方水平性半盲と対光反射減弱が出現した．眼窩MRIのT₂強調画像で右視神経腫大，視神経上半側の高信号，ガドリニウム造影増強効果を認め，抗AQP4抗体陽性と併せ視神経脊髄炎関連疾患（neuromyelitis optica spectrum disorders，以下NMOSDと略記）と診断した．NMOSDの初発症状として頭痛がみられることがあるので，鑑別の際に念頭に置く必要がある．