Dagenais Renée V E, Su Victoria C H, Quon Bradley S
Adult Cystic Fibrosis Program, St. Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada.
Department of Medicine, University of British Columbia, Vancouver, BC V6Z 1Y6, Canada.
J Clin Med. 2020 Dec 23;10(1):23. doi: 10.3390/jcm10010023.
Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies target the underlying cause of cystic fibrosis (CF), and are generally well-tolerated; however, real-world studies indicate the frequency of discontinuation and adverse events (AEs) may be higher than what was observed in clinical trials. The objectives of this systematic review were to summarize real-world AEs reported for market-available CFTR modulators (i.e., ivacaftor (IVA), lumacaftor/ivacaftor (LUM/IVA), tezacaftor/ivacaftor (TEZ/IVA), and elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA)), and to identify ways in which the pharmacist on CF healthcare teams may contribute to mitigating and managing these AEs. The MEDLINE, EMBASE, CINAHL, and Web of Science Core Collection online databases were searched from 2012 to Aug 1, 2020. Full manuscripts or conference abstracts of observational studies, case series, and case reports were eligible for inclusion. The included full manuscripts and conference abstracts comprised of 54 observational studies, 5 case series, and 9 case reports. The types of AEs reported generally aligned with what have been observed in clinical trials. LUM/IVA was associated with a higher frequency of respiratory-related AE and discontinuation in real-world studies. A signal for mental health and neurocognitive AEs was identified with all 4 CFTR modulators. A systematic approach to monitoring for AEs in people with CF on CFTR modulators in the real-world setting is necessary to help better understand potential AEs, as well as patient characteristics that may be associated with higher risk of certain AEs. Pharmacists play a key role in the safe initiation and monitoring of people with CF on CFTR modulator therapies.
囊性纤维化跨膜传导调节因子（CFTR）调节剂疗法针对囊性纤维化（CF）的根本病因，且通常耐受性良好；然而，真实世界研究表明，停药频率和不良事件（AE）可能高于临床试验中的观察结果。本系统评价的目的是总结已上市CFTR调节剂（即依伐卡托（IVA）、鲁玛卡托/依伐卡托（LUM/IVA）、替扎卡托/依伐卡托（TEZ/IVA）和艾列卡托/替扎卡托/依伐卡托（ELX/TEZ/IVA））报告的真实世界不良事件，并确定CF医疗团队中的药剂师可通过哪些方式帮助减轻和管理这些不良事件。检索了2012年至2020年8月1日的MEDLINE、EMBASE、CINAHL和科学网核心合集在线数据库。观察性研究、病例系列和病例报告的全文手稿或会议摘要符合纳入标准。纳入的全文手稿和会议摘要包括54项观察性研究、5个病例系列和9篇病例报告。报告的不良事件类型总体上与临床试验中观察到的一致。在真实世界研究中，LUM/IVA与更高频率的呼吸道相关不良事件和停药有关。在所有4种CFTR调节剂中均发现了心理健康和神经认知不良事件的信号。在真实世界环境中，采用系统方法监测接受CFTR调节剂治疗的CF患者的不良事件，有助于更好地了解潜在不良事件以及可能与某些不良事件高风险相关的患者特征。药剂师在CF患者安全启动和监测CFTR调节剂治疗中发挥着关键作用。
