An Observational Study of Outcomes and Tolerances in Patients with Cystic Fibrosis Initiated on Lumacaftor/Ivacaftor
An Observational Study of Outcomes and Tolerances in Patients with Cystic Fibrosis Initiated on Lumacaftor/Ivacaftor
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DOI：
10.1513/annalsats.201701-058oc
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发表时间：
2017-11-01
影响因子：
8.3
通讯作者：
Lechtzin, Noah
中科院分区：
文献类型：
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作者：
Jennings, Mark T.;Dezube, Rebecca;Lechtzin, Noah
理由：2015年7月，美国食品和药物管理局批准lumacaftor/ivacaftor用于囊性纤维化（CF）患者。该药物靶向CFTR蛋白中由F508del CFTR突变引起的主要缺陷。目的：由于在临床试验之外，这种疗法的经验有限，本研究旨在研究这种新药在CF人群中的临床经验。结果：回顾性队列研究，在约翰霍普金斯CF中心随访的开始使用lumacaftor/ ivacaftor治疗的个体。患者从用药前1年到用药后11个月随访。主要的排除标准包括以前通过参加临床试验暴露于lumacaftor/ivacaftor。在116名确定开始lumacaftor/ivacaftor治疗的个体中，46名（39.7%）报告了与lumacaftor/ivacaftor相关的不良反应，其中绝大多数（82.2%）为肺部不良反应，20名（17.2%）因不良反应而停止使用lumacaftor/ivacaftor。预测FEV1%的平均变化为0.11%（范围：-39%至+20%；P = 0.9）。19名患者在治疗前FEV1%预测值为40%或更低，该亚组中报告不良反应的患者比例较高（57.9%），停用lumacaftor/ivacaftor的患者比例较高（31.6%）。女性与较高的停药几率相关（调整后的优势比为3.12,95%可信区间为1.04-9.38）。结论：本研究强调了新暴露于lumacaftor/ivacaftor的CF人群中不良反应的患病率，并显示出相对较高的药物不耐受率。
Rationale: In July 2015, the U.S. Food and Drug Administration approved lumacaftor/ivacaftor for use in patients with cystic fibrosis (CF). This drug targets the primary defect in the CFTR protein that is conferred by the F508del CFTR mutation.Objective: As there is limited experience with this therapy outside of clinical trials, this study aims to examine the clinical experience of this new drug in a population with CF.Results: Retrospective cohort study of individuals followed at the Johns Hopkins CF Center who initiated treatment with lumacaftor/ ivacaftor. Patients were followed from 1 year before drug initiation to up to 11 months postinitiation. Key exclusion criteria include previous exposure to lumacaftor/ivacaftor through participation in a clinical trial. Of 116 individuals identified who started lumacaftor/ivacaftor treatment, 46 (39.7%) reported adverse effects related to lumacaftor/ivacaftor, with the vast majority (82.2%) being pulmonary adverse effects, and 20 (17.2%) discontinued lumacaftor/ivacaftor because of adverse effects. The mean change in FEV1% predicted was 0.11% (range: -39% to +20%; P = 0.9). Nineteen individuals had an FEV1% predicted of 40% or less before treatment, and there was a higher percentage of patients in this subgroup who reported adverse effects (57.9%) and a higher percentage of patients who discontinued lumacaftor/ivacaftor (31.6%). Female sex was associated with a higher odds of drug discontinuation (adjusted odds ratio, 3.12, 95% confidence interval, 1.04-9.38).Conclusions: This study highlights the prevalence of adverse effects in a CF population newly exposed to lumacaftor/ivacaftor and demonstrates a relatively high rate of drug intolerance.