Lei Jin1, Dingxian He1, Hongxi Chen2, Hongyu Zhou2, Quantao Zeng3, Song Tan3, Jianquan Shi4, Ying Liu5, Zhangyu Zou6, Jie Song1, Chong Yan1, Xiao Huan1, Yuan Wang7, Lei Yang8, Jianying Xi1, Zongtai Wu9, Jianming Zheng10, Chongbo Zhao1, Xianglin Chu11, Sushan Luo1
1Huashan Rare Disease Center and Department of Neurology, Huashan Hospital, Shanghai Medical College, National Center for Neurological Disorders, Fudan University, Shanghai, China;
2Department of Neurology, West China Hospital, Sichuan University, Chengdu, China;
3Department of Neurology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China;
4Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China;
5Department of Neurology, the Second Hospital of Dalian Medical University, Dalian, China;
6Department of Neurology, Fujian Medical University Union Hospital, Fuzhou, China;
7Department of Blood Transfusion, Huashan Hospital, Fudan University, Shanghai, China;
8Department of Neurosurgery & Neurocritical Care, Huashan Hospital Fudan University, Shanghai, China;
9Faculty of Biology, University of Cambridge, Cambridge, UK;
10Department of Infectious Diseases, Huashan Hospital, National Medical Center for Infectious Diseases, Fudan University, Shanghai, China;
11Department of Thoracic Surgery, Huashan Hospital, Fudan University, Shanghai, China
Correspondence to: Sushan Luo, PhD. Huashan Rare Disease Center and Department of Neurology, Huashan Hospital, Shanghai Medical College, National Center for Neurological Disorders, Fudan University, Shanghai, No. 12, Urumqi Middle Road, Shanghai 200040, China. Email: luosushan@fudan.edu.cn.
Background: Thymoma-associated myasthenia gravis (TAMG) is frequently resistant to conventional treatment and portends poorer prognosis. Targeted biologic therapies have been implemented for treating generalised myasthenia gravis (MG), evidence for their long-term safety and efficacy in TAMG remains scarce. To investigate the long-term safety and efficacy of targeted biologics in patients with TAMG, we conducted this real-world study.
Methods: In this multicenter, retrospective real-world study, we enrolled TAMG patients treated with maintenance targeted biologic therapy at six neuromuscular centers in China from May 2023 to May 2024. Therapies comprised the anti-CD20 monoclonal antibody (rituximab), the C5 inhibitor (eculizumab), and the neonatal Fc receptor (FcRn) antagonist (efgartigimod). Survivors were followed for at least 1 year, while all deaths were captured regardless of follow-up duration. Stable treatment was defined as rituximab at least once every 6 months, or efgartigimod/eculizumab at least once per month. The primary outcome was the proportion achieving minimal symptom expression (MSE). Secondary outcomes included rates of adverse events (AEs), myasthenic crises (MC) or impending crises, and mortality.
Results: Twenty-two patients (mean age 50.3±12.8 years; median disease duration 12.5 months) were analyzed over a mean follow-up of 13.0±5.5 months. Thymectomy was performed in 95.5% of cases, with 59.1% receiving adjuvant chemoradiotherapy. Biologic therapy commenced perioperatively in 18.2%, and 81.8% initiated treatment amid acute exacerbations or crises. Histopathology was dominated by World Health Organization (WHO) type B2 thymoma (40.9%) with Masaoka stage IV (54.5%). After treatment, fell markedly (13.14±5.83 to 3.35±4.66 at 1 year), and median daily steroid dose declined from 45 to 10 mg (Figure 1A). MSE was achieved in 40.9%, lasting on average 230 days. AEs occurred in 59.1%, chiefly infections (50.0%). Both MC (from 63.6% to 22.7%) and impending crisis (from 18.2% to 0%) rates declined. At 1 year, 16 patients (72.7%) attained “Improved” or “Minimal manifestations”, while 5 patients (22.7%) died during follow-up (Figure 1B).
Conclusions: Maintenance targeted biologic therapy substantially improves clinical outcomes, reduces steroid burden and lowers the risk of MC or impending crisis in TAMG, with an acceptable safety profile. These findings support its long-term use in this challenging population.
Keywords: Thymoma; myasthenia gravis (MG); biologics; minimal symptom expression (MSE)
