针对庞贝病婴儿和幼儿进行个体化改良脱敏治疗，以及对阿糖苷酶α输注产生严重反应的方法。
An individually, modified approach to desensitize infants and young children with Pompe disease, and significant reactions to alglucosidase alfa infusions.
机构信息
Department of Pediatrics, Division of Medical Genetics, Duke University Medical, Center, Durham, NC 27710, USA.
出版信息
Mol Genet Metab. 2011 Sep-Oct;104(1-2):118-22. doi: 10.1016/j.ymgme.2011.07.004. Epub 2011 Jul 13.
PURPOSE
Pompe disease (PD) is a progressive metabolic myopathy for which the only available treatment is alglucosidase alfa (Myozyme®). Enzyme replacement therapy (ERT) has improved ventilator-free survival, and cardiac and motor functions in patients with infantile PD. However, for an adequate response to occur, a large amount of enzymes must be infused. In some patients, this may be problematic due to infusion-associated reactions (IARs) occurring in approximately 50% of patients receiving alglucosidase alfa infusions. Whilst the majority of these reactions are mild, life threatening hypersensitivity reactions may occur in some patients. In these patients desensitization is indicated to enable continued ERT safely. Infants and young children with PD and significant infusion reactions pose unique management challenges because of their young age, limited communication skills, variable presentation and underlying cardiomyopathy.
METHODS/SUBJECTS: In 2 patients with PD who experienced significant ERT-related reactions: an infant (IgE positive) and a young child (IgE negative), we implemented a desensitization protocol, that started by administering a reduced dose of alglucosidase alfa (10 mg/kg weekly) instead of the standard (20 mg/kg bi-weekly) using serial micro-dilutions that were individually prepared and delivered in a highly regulated manner based on patients' clinical manifestations and tolerance.
RESULTS
Successful desensitization was achieved in both patients, allowing them to eventually continue to receive the full dose of ERT safely.
CONCLUSION
Therapeutic demands in infants and young children with PD need to be tailored according to the patient presentation, and underlying cardiac and fluid-volume status. Desensitization allowed both patients to continue alglucosidase alfa treatment at the recommended dose without prolonged interruption of therapy, or further reactions.
目的
庞贝病（PD）是一种进行性代谢性肌病，目前唯一可用的治疗方法是阿糖苷酶α（Myozyme®）。酶替代疗法（ERT）改善了婴儿 PD 患者的呼吸机无依赖生存率和心脏及运动功能。然而，为了获得充分的反应，必须输注大量的酶。在某些患者中，由于接受阿糖苷酶α输注的患者中约有 50%发生输注相关反应（IAR），这可能会成为一个问题。虽然大多数这些反应是轻度的，但一些患者可能会发生危及生命的过敏反应。在这些患者中，需要脱敏以安全地继续 ERT。患有 PD 且存在严重输注反应的婴儿和幼儿由于年龄较小、沟通能力有限、表现多变以及潜在的心肌病，给管理带来了独特的挑战。
方法/研究对象：在 2 名经历过严重 ERT 相关反应的 PD 患者（1 名婴儿[IgE 阳性]和 1 名幼儿[IgE 阴性]）中，我们实施了脱敏方案，开始时使用较低剂量的阿糖苷酶α（10 mg/kg/周）代替标准剂量（20 mg/kg/两周），采用连续微稀释法，根据患者的临床表现和耐受性个体化制备和以高度规范的方式给药。
结果
两名患者均成功脱敏，从而能够安全地继续接受全剂量 ERT。
结论
需要根据患者的临床表现、潜在的心脏和液体容量状况，为 PD 婴儿和幼儿量身定制治疗需求。脱敏使两名患者能够继续接受阿糖苷酶α治疗，剂量达到推荐剂量，而无需长时间中断治疗或出现进一步的反应。
Zotero 插件