Department of Neurology, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Department of Neurology, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Eur J Paediatr Neurol. 2018 Nov;22(6):1066-1073. doi: 10.1016/j.ejpn.2018.06.007. Epub 2018 Jul 4.
To evaluate the safety of mTOR inhibitors (sirolimus or everolimus) in infants and very young children with tuberous sclerosis complex (TSC) under two years of age.
Study design was retrospective to capture medical record data from 52 international TSC Centres who initiated treatment with sirolimus or everolimus in TSC children before the age of two years. Data collection included demographic and clinical information including reason(s) for initiating treatment with mTOR inhibitors, treatment duration, dosing, and corresponding serum trough levels, response to treatment, and adverse events (AE).
19 of 52 (37%) TSC Centres reported treatment of at least one child with TSC under the age of two years with everolimus or sirolimus. Treatment-related data were provided for 45 patients meeting inclusion criteria. Everolimus was utilised 87% of the time, compared to 24% for sirolimus (5 subjects, 11%, were treated separately with both). Refractory epilepsy (45%) was the most common primary reason for initiating treatment and treatment was initiated on average at 11.6 ± 7.6 months of age. At least one AE, suspected or definitely treatment-related, occurred in 35 of 45 (78%) treated subjects. Most AEs were mild (Grade 1) or moderate (Grade 2) in severity and most commonly related to infections. Severe AE (Grade 3) was reported in 7 subjects (20%) and no life-threatening AE (Grade 4) or death/disability (Grade 5) was reported. Treatment was discontinued due to an AE in 9 of 45 (20%).
Everolimus, and to a lesser extent sirolimus, are increasingly being used to treat TSC infants and very young children for multiple TSC-associated clinical indications. While AEs were common, most were not severe and did not prevent continued treatment in the majority of this younger population.
评估在两岁以下患有结节性硬化症（TSC）的婴儿和非常年幼的儿童中使用 mTOR 抑制剂（西罗莫司或依维莫司）的安全性。
该研究设计为回顾性，从 52 家国际 TSC 中心获取病历数据，这些中心在两岁以下的 TSC 儿童中开始使用西罗莫司或依维莫司进行治疗。数据收集包括人口统计学和临床信息，包括开始使用 mTOR 抑制剂治疗的原因、治疗持续时间、剂量和相应的血药谷浓度、治疗反应和不良事件（AE）。
在 52 家 TSC 中心中，有 19 家（37%）报告了至少有一名两岁以下的 TSC 儿童使用依维莫司或西罗莫司进行治疗。符合纳入标准的 45 名患者提供了与治疗相关的数据。依维莫司的使用时间占 87%，而西罗莫司的使用时间占 24%（5 名患者，11%，分别单独使用两种药物）。难治性癫痫（45%）是开始治疗的最常见主要原因，治疗平均在 11.6±7.6 个月龄开始。在接受治疗的 45 名患者中，有 35 名（78%）至少发生了一次 AE，怀疑或肯定与治疗相关。大多数 AE 的严重程度为轻度（1 级）或中度（2 级），最常见的是与感染有关。7 名患者（20%）发生严重 AE（3 级），无危及生命的 AE（4 级）或死亡/残疾（5 级）报告。由于 AE，有 9 名（20%）患者停止了治疗。
依维莫司，在较小程度上是西罗莫司，越来越多地用于治疗 TSC 婴儿和非常年幼的儿童，用于多种 TSC 相关的临床指征。虽然 AE 很常见，但大多数并不严重，并且在大多数这一年龄较小的人群中没有阻止继续治疗。
