Off-label use of tacrolimus in children with Henoch-Schonlein purpura nephritis: a pilot study
Off-label use of tacrolimus in children with Henoch-Schonlein purpura nephritis: a pilot study
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DOI：
10.1136/archdischild-2017-313788
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发表时间：
2018-08-01
影响因子：
5.2
通讯作者：
Zhao, Wei
中科院分区：
文献类型：
--
作者：
Zhang, Dong-Feng;Hao, Guo-Xiang;Zhao, Wei
背景：他克莫司用于儿童过敏性紫癜性肾炎(HSPN)的非标签治疗，循证数据有限。根据临床经验和作用机制，他克莫司可能被推广用于治疗儿童HSPN。这项先导性研究的目的是评估其有效性和安全性，并探索CYP3A5基因型的潜在影响。方法将接受他克莫司作为经验性治疗的HSPN儿童纳入这项前瞻性、观察性研究。疗效分为完全缓解、部分缓解或无反应。研究期间和研究后对药物暴露的一般安全数据分析包括不良事件、停药原因、死亡、实验室数据和生命体征。采用高效液相色谱-串联质谱法测定谷峰浓度。结果20例患者的平均年龄为7.5(SD 2.1)岁，参与了整个研究过程。治疗6个月后，12例患者达到完全缓解，8例患者达到部分缓解。没有患者因不良事件而停止他克莫司治疗，也没有与药物相关的不良事件被证明与他克莫司治疗有因果关系。携带CYP3A5*1等位基因儿童的剂量调整谷浓度显著高于携带CYP3A5*3/*3等位基因的儿童(170.7+/-100.9 vs79.8+/-47.4(ng/mL)/(mg/kg))。结论他克莫司可能是一种治疗儿童过敏性肾炎的有效药物。CYP3A5基因多态性对他克莫司浓度有显著影响。
Background Tacrolimus is used off-label in the treatment of Henoch-Schonlein purpura nephritis (HSPN) in children, with limited evidence-based data. Based on clinical empirical experience and mechanism of action, tacrolimus might be promoted as treatment for childhood HSPN. The objectives of this pilot study were to assess its effectiveness and safety, and to explore the potential impact of CYP3A5 genotype.Methods Children with HSPN receiving tacrolimus as empirical treatment were included in this prospective, observational study. Effectiveness was classified as complete remission, partial remission or non-response. General safety data analyses during and after study drug exposure included adverse events, reasons for discontinuation, deaths, laboratory data and vital signs. Trough concentration was determined using high-performance liquid chromatography with tandem mass spectrometry. Pharmacogenetic analysis was performed on the CYP3A5 gene.Results A total of 20 patients with a mean age of 7.5 (SD 2.1) years participated in the whole process of the study. Twelve patients reached complete remission and eight patients reached partial remission at the end of 6-month treatment. No patients discontinued tacrolimus treatment due to adverse events, and no drug-related adverse events were shown to have a causal association with tacrolimus therapy. Dose-adjusted trough concentration was significantly higher in children with CYP3A5*1 allele as compared with patients with CYP3A5*3/*3 genotype (170.7 +/- 100.9 vs 79.8 +/- 47.4 (ng/mL)/(mg/kg)).Conclusion This pilot study showed that tacrolimus might be an effective and well-tolerated drug for the treatment of HSPN in children. CYP3A5 polymorphism had a significant impact on tacrolimus concentration.