Safety and efficacy of treatment with lumacaftor in combination with ivacaftor in younger patients with cystic fibrosis.
Safety and efficacy of treatment with lumacaftor in combination with ivacaftor in younger patients with cystic fibrosis.
复制标题
lumacaftor 与 ivacaftor 联合治疗年轻囊性纤维化患者的安全性和有效性。
DOI：
10.1080/17476348.2019.1602040
复制
发表时间：
2019
影响因子：
3.9
通讯作者：
Rubenstein,RonaldC
中科院分区：
文献类型：
--
作者：
Cheng,PiChun;Alexiou,Stamatia;Rubenstein,RonaldC
前言：囊性纤维化是高加索人群中最常见的常染色体隐性遗传病，全世界约有7万人患病。功能性囊性纤维化跨膜传导调节因子(CFTR)的缺乏导致肺、胃肠道和汗腺上皮液运输的失调。研究范围：最常见的致病CFTR突变F508del存在于75%以上的患者中；针对F508del功能的治疗有望降低大多数CF患者的发病率和死亡率。Lumacaftor可以纠正F508del在细胞内的异常运输，iVacaftor可以增强CFTR功能，两者的组合被称为OrkbiTM，是第一种被批准用于治疗F508del纯合子患者的CF的药物。根据开放标签的3期临床安全性研究的最新数据，OrkbiTM目前被批准用于2岁及2岁以上的儿童。专家观点：OrkbiTM适度改善F508del纯合子的CF患者的临床结果，并且具有合理的安全性。这是治疗CF的一个重大进展，但还需要进一步的进展，可能需要在这种联合小分子治疗的基础上增加第三种药物，以扩大目标人群和有益效果。
Introduction: Cystic fibrosis (CF) is the most common autosomal recessive disorder among Caucasians affecting ~70,000 people worldwide. The lack of functional cystic fibrosis transmembrane conductance regulator (CFTR) causes dysregulation of epithelial fluid transport in the lungs, gastrointestinal tract, and sweat glands.Areas covered: The most common disease-causing CFTR mutation, F508del, is present in over 75% of those affected;. therapies targeting F508del function have the promise to reduce morbidity and mortality in the majority of patients with CF. The combination of lumacaftor, which corrects the aberrant intracellular trafficking of F508del, and ivacaftor, which potentiates CFTR function, is known as OrkambiTM, and is the first drug approved for the treatment of CF in patients who are F508del-homozygotes. OrkambiTMis currently approved for use in children aged 2 and older based on recent data from open-label Phase 3 clinical safety studies.Expert opinion: OrkambiTMmodestly improves clinical outcomes for people with CF who are F508del-homozygotes, and does so with a reasonable safety profile. This is a major advance in therapy for CF, but further advances are needed, perhaps with the addition of a third agent to this combination small molecule therapy, in order to expand both the targeted population and beneficial effects.