Bacalhau Mafalda, Camargo Mariana, Magalhães-Ghiotto Grace A V, Drumond Sybelle, Castelletti Carlos Henrique M, Lopes-Pacheco Miquéias
Biosystems & Integrative Sciences Institute (BioISI), Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal.
Department of Surgery, Division of Urology, Sao Paulo Federal University, Sao Paulo 04039-060, SP, Brazil.
Pharmaceuticals (Basel). 2023 Mar 8;16(3):410. doi: 10.3390/ph16030410.
Cystic fibrosis (CF) is a potentially fatal monogenic disease that causes a progressive multisystemic pathology. Over the last decade, the introduction of CF transmembrane conductance regulator (CFTR) modulator drugs into clinical practice has profoundly modified the lives of many people with CF (PwCF) by targeting the fundamental cause of the disease. These drugs consist of the potentiator ivacaftor (VX-770) and the correctors lumacaftor (VX-809), tezacaftor (VX-661), and elexacaftor (VX-445). In particular, the triple combination of CFTR modulators composed of elexacaftor, tezacaftor, and ivacaftor (ETI) represents a life-changing therapy for the majority of PwCF worldwide. A growing number of clinical studies have demonstrated the safety and efficacy of ETI therapy in both short- and long-term (up to two years of follow-up to date) and its ability to significantly reduce pulmonary and gastrointestinal manifestations, sweat chloride concentration, exocrine pancreatic dysfunction, and infertility/subfertility, among other disease signs and symptoms. Nevertheless, ETI therapy-related adverse effects have also been reported, and close monitoring by a multidisciplinary healthcare team remains vital. This review aims to address and discuss the major therapeutic benefits and adverse effects reported by the clinical use of ETI therapy for PwCF.
囊性纤维化（CF）是一种潜在致命的单基因疾病，可导致进行性多系统病理改变。在过去十年中，将囊性纤维化跨膜传导调节因子（CFTR）调节剂药物引入临床实践，通过针对该疾病的根本原因，深刻改变了许多囊性纤维化患者（PwCF）的生活。这些药物包括增效剂依伐卡托（VX-770）以及校正剂鲁马卡托（VX-809）、替扎卡托（VX-661）和艾列卡托（VX-445）。特别是，由艾列卡托、替扎卡托和依伐卡托（ETI）组成的CFTR调节剂三联组合，对全球大多数PwCF来说是一种改变生活的疗法。越来越多的临床研究证明了ETI疗法在短期和长期（迄今为止长达两年的随访）中的安全性和有效性，以及它显著减轻肺部和胃肠道表现、汗液氯化物浓度、外分泌胰腺功能障碍和不孕/不育等其他疾病体征和症状的能力。然而，也有报道称存在与ETI疗法相关的不良反应，多学科医疗团队的密切监测仍然至关重要。本综述旨在探讨和讨论临床使用ETI疗法治疗PwCF所报告的主要治疗益处和不良反应。
