背景:越来越多的针对肌萎缩蛋白病的新治疗策略的临床试验正在进行中或正在考虑中。关于这种情况的自然进展的详细数据对于评估新药的有效性至关重要。然而,缺乏有关自然过程的长期数据以及在中国如何管理的数据。在这项研究中,我们提供临床和分子研究的全面概述,以及中国人群的治疗结果。
方法:回顾性分析了2011年8月至2021年8月所有肌营养不良病患者的机构数据。数据包括地理分布,诊断时的年龄,分子发现,和治疗选择,比如皮质类固醇,心脏干预,和临床结果。
结果:总计,2097例肌营养不良症患者,包括1703例Duchenne型肌营养不良(DMD),311例Becker肌营养不良(BMD),中间型肌营养不良(IMD)46例,和37例归类为“未决”(表型未确定的个体),2011年8月至2021年8月在复旦大学附属儿童医院的肌营养不良病数据库中注册。鉴定的变异包括外显子缺失(66.6%),外显子重复(10.7%),无义变体(10.3%),剪接位点变异体(4.5%),小缺失(3.5%),小插入/重复(1.8%),和错义变体(0.9%)。鉴定了四个深内含子变体和两个倒位变体。关于治疗,54.4%的DMD患者和39.1%的IMD患者接受了糖皮质激素治疗.在接受糖皮质激素治疗的DMD患者中,步行失败的中位年龄为2.5年后。总的来说,至少为7.4%的DMD患者开了一种心脏药物,8.3%的IMD患者,2.6%的BMD患者。此外,4名DMD患者需要呼吸机支持.在55.3%的DMD患者中发现了外显子跳跃治疗的资格,12.9%,10%,这些患者中有9.6%分别符合跳过外显子51、53和45的条件。
结论:这是评估中国肌萎缩蛋白病自然史的最大研究之一,这特别有利于招募符合条件的患者进行临床试验,并提供真实世界的数据以支持药物开发。
BACKGROUND: An increasing number of clinical trials for new therapeutic strategies are underway or being considered for dystrophinopathy. Having detailed data on the natural progression of this condition is crucial for assessing the effectiveness of new drugs. However, there\'s a lack of data regarding the long-term data on the natural course and how it\'s managed in China. In this study, we offer a comprehensive overview of clinical and molecular findings, as well as treatment outcomes in the Chinese population.
METHODS: Institutional data on all patients with dystrophinopathy from August 2011 to August 2021 were retrospectively reviewed. The data included geographic distribution, age at diagnosis, molecular findings, and treatment options, such as corticosteroids, cardiac interventions, and clinical outcomes.
RESULTS: In total, 2097 patients with dystrophinopathy, including 1703 cases of Duchenne muscular dystrophy (DMD), 311 cases of Becker muscular dystrophy (BMD), 46 cases of intermediate muscular dystrophy (IMD), and 37 cases categorized as \"pending\" (individuals with an undetermined phenotype), were registered in the Children\'s Hospital of Fudan University database for dystrophinopathy from August 2011 to August 2021. The spectrum of identified variants included exonic deletions (66.6%), exonic duplications (10.7%), nonsense variants (10.3%), splice-site variants (4.5%), small deletions (3.5%), small insertions/duplications (1.8%), and missense variants (0.9%). Four deep intronic variants and two inversion variants were identified. Regarding treatment, glucocorticoids were administered to 54.4% of DMD patients and 39.1% of IMD patients. The median age at loss of ambulation was 2.5 years later in DMD patients who received glucocorticoid treatment. Overall, one cardiac medicine at least was prescribed to 7.4% of DMD patients, 8.3% of IMD patients, and 2.6% of BMD patients. Additionally, ventilator support was required by four DMD patients. Eligibility for exon skipping therapy was found in 55.3% of DMD patients, with 12.9%, 10%, and 9.6% of these patients being eligible for skipping exons 51, 53, and 45, respectively.
CONCLUSIONS: This is one of the largest studies to have evaluated the natural history of dystrophinopathy in China, which is particularly conducive to the recruitment of eligible patients for clinical trials and the provision of real-world data to support drug development.