依维莫司
西罗莫司
结节性硬化
医学
不利影响
加药
mTOR抑制剂的发现与发展
儿科
内科学
PI3K/AKT/mTOR通路
病理
生物化学
化学
细胞凋亡
作者
Darcy A. Krueger,Jamie K. Capal,Paolo Curatolo,Orrin Devinsky,Kevin C. Ess,Michal Tzadok,Mary Kay Koenig,Vinodh Narayanan,Federico Ramos,Sergiusz Jóźwiak,Petrus de Vries,Anna Jansen,Michael Wong,David Mowat,John A. Lawson,Stephanie Bruns,David Neal Franz
标识
DOI:10.1016/j.ejpn.2018.06.007
摘要
Objective 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. Methods 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). Results 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%). Conclusions 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.
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