针对杜兴氏肌肉萎缩症患者的 Delandistrogene Moxeparvovec 基因疗法后特定不良事件的处理。

IF 3.2 4区 医学 Q2 CLINICAL NEUROLOGY Journal of neuromuscular diseases Pub Date : 2024-04-11 DOI:10.3233/JND-230185
C. Zaidman, N. Goedeker, Amal A Aqul, Russell J. Butterfield, Anne M. Connolly, Ronald G Crystal, Kara E Godwin, Kan N Hor, Katherine D. Mathews, Crystal M. Proud, Elizabeth Kula Smyth, A. Veerapandiyan, Paul B Watkins, J. R. Mendell
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Delandistrogene moxeparvovec (Sarepta Therapeutics, Cambridge, MA) is indicated for treatment of ambulatory pediatric patients aged 4 through 5 years with DMD who have an indicated mutation in the DMD gene.\n\n\nOBJECTIVE\nEvidence-based considerations for management of potential adverse events following gene therapy treatment for DMD are lacking in clinical literature. Our goal was to provide interdisciplinary consensus considerations for selected treatment-related adverse events (TRAEs) (vomiting, acute liver injury, myocarditis, and immune-mediated myositis) that may arise following gene therapy dosing with delandistrogene moxeparvovec.\n\n\nMETHODS\nAn interdisciplinary panel of 12 specialists utilized a modified Delphi process to develop consensus considerations for the evaluation and management of TRAEs reported in delandistrogene moxeparvovec clinical studies. Panelists completed 2 Questionnaires prior to gathering for an in-person discussion. 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引用次数: 0

摘要

背景杜氏肌营养不良症(DMD)是一种罕见的退行性隐性 X 连锁神经肌肉疾病。编码肌营养不良蛋白的基因突变会导致功能性肌营养不良蛋白的缺失。DMD 患者会表现出进行性肌无力,导致丧失行动能力和肢体功能、呼吸功能不全和心肌病,并累及多个器官。腺相关病毒载体介导的基因疗法旨在生产功能性肌营养不良蛋白,是一种新的治疗策略。Delandistrogene moxeparvovec(Sarepta Therapeutics,马萨诸塞州剑桥市)适用于治疗患有 DMD 的 4 至 5 岁非卧床儿童患者,这些患者的 DMD 基因存在指定的突变。我们的目标是为选定的治疗相关不良事件(TRAEs)(呕吐、急性肝损伤、心肌炎和免疫介导的肌炎)提供跨学科共识,这些不良事件可能会在使用 delandistrogene moxeparvovec 进行基因治疗后出现。方法由 12 位专家组成的跨学科小组采用改良的德尔菲流程,为 delandistrogene moxeparvovec 临床研究中报告的 TRAEs 的评估和管理制定共识。专家小组成员在进行面对面讨论之前填写了 2 份问卷。结果小组成员一致认为,基线评估的选择应参考个体临床适应症、治疗提供者的判断以及处方信息。治疗 TRAE 的皮质类固醇剂量应通过考虑每个适应症的风险与收益进行优化。结论德尔菲小组就评估和管理接受溴化阻塞素莫西帕罗韦治疗的患者可能出现的 TRAEs(包括呕吐、急性肝损伤、心肌炎和免疫介导的肌炎)达成了共识。
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Management of Select Adverse Events Following Delandistrogene Moxeparvovec Gene Therapy for Patients With Duchenne Muscular Dystrophy.
BACKGROUND Duchenne muscular dystrophy (DMD) is a rare, degenerative, recessive X-linked neuromuscular disease. Mutations in the gene encoding dystrophin lead to the absence of functional dystrophin protein. Individuals living with DMD exhibit progressive muscle weakness resulting in loss of ambulation and limb function, respiratory insufficiency, and cardiomyopathy, with multiorgan involvement. Adeno-associated virus vector-mediated gene therapy designed to enable production of functional dystrophin protein is a new therapeutic strategy. Delandistrogene moxeparvovec (Sarepta Therapeutics, Cambridge, MA) is indicated for treatment of ambulatory pediatric patients aged 4 through 5 years with DMD who have an indicated mutation in the DMD gene. OBJECTIVE Evidence-based considerations for management of potential adverse events following gene therapy treatment for DMD are lacking in clinical literature. Our goal was to provide interdisciplinary consensus considerations for selected treatment-related adverse events (TRAEs) (vomiting, acute liver injury, myocarditis, and immune-mediated myositis) that may arise following gene therapy dosing with delandistrogene moxeparvovec. METHODS An interdisciplinary panel of 12 specialists utilized a modified Delphi process to develop consensus considerations for the evaluation and management of TRAEs reported in delandistrogene moxeparvovec clinical studies. Panelists completed 2 Questionnaires prior to gathering for an in-person discussion. Consensus was defined as a majority (≥58% ; 7/12) of panelists either agreeing or disagreeing. RESULTS Panelists agreed that the choice of baseline assessments should be informed by individual clinical indications, the treating provider's judgment, and prescribing information. Corticosteroid dosing for treatment of TRAEs should be optimized by considering individual risk versus benefit for each indication. In all cases involving patients with a confirmed TRAE, consultations with appropriate specialists were suggested. CONCLUSIONS The Delphi Panel established consensus considerations for the evaluation and management of potential TRAEs for patients receiving delandistrogene moxeparvovec, including vomiting, acute liver injury, myocarditis, and immune-mediated myositis.
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来源期刊
Journal of neuromuscular diseases
Journal of neuromuscular diseases Medicine-Neurology (clinical)
CiteScore
5.10
自引率
6.10%
发文量
102
期刊介绍: The Journal of Neuromuscular Diseases aims to facilitate progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias and myositis). The journal publishes research reports, reviews, short communications, letters-to-the-editor, and will consider research that has negative findings. The journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.
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