Terlizzi Vito, Lopes-Pacheco Miquéias
Department of Pediatric Medicine, Cystic Fibrosis Regional Reference Center, Meyer Children's Hospital IRCCS, Viale Gaetano Pieraccini 24, Florence, Italy.
Department of Pediatrics, Cystic Fibrosis and Airway Disease Research Center, Emory University School of Medicine, Atlanta, GA, USA.
Ther Adv Respir Dis. 2025 Jan-Dec;19:17534666251323194. doi: 10.1177/17534666251323194. Epub 2025 Mar 31.
Over the past decade, major clinical advances have been made in the healthcare and therapeutic development for cystic fibrosis (CF), a lethal genetic disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. CFTR modulators represent innovative treatments that directly target the primary defects in the mutated CFTR protein and have demonstrated significant clinical benefits for many people with CF (pwCF) who are eligible for these treatments. In particular, the triple combination therapy composed of elexacaftor, tezacaftor, and ivacaftor (ETI) has changed the CF therapeutic landscape by significantly improving lung function, quality of life, and predicted survival rates. Here, we provided a comprehensive summary of the impact of ETI on clinical outcomes and the need for further research on long-term efficacy, side effects, pregnancy, possible drug-drug interactions, and extra-pulmonary manifestations. Moreover, a significant number of pwCF are unresponsive to these drugs or cannot afford their high costs. We, therefore, discussed health inequity issues and alternative therapeutic strategies under development aiming to obtain effective therapies for all pwCF.
在过去十年中，囊性纤维化（CF）的医疗保健和治疗开发取得了重大临床进展。CF是一种致命的遗传疾病，由编码CF跨膜电导调节因子（CFTR）蛋白的基因突变引起。CFTR调节剂是一种创新疗法，直接针对突变的CFTR蛋白的主要缺陷，已证明对许多符合这些治疗条件的CF患者（pwCF）具有显著的临床益处。特别是，由依列卡托、替扎卡托和依伐卡托（ETI）组成的三联联合疗法显著改善了肺功能、生活质量和预测生存率，从而改变了CF的治疗格局。在此，我们全面总结了ETI对临床结果的影响，以及对其长期疗效、副作用、妊娠、可能的药物相互作用和肺外表现进行进一步研究的必要性。此外，相当数量的pwCF对这些药物无反应或负担不起其高昂费用。因此，我们讨论了健康不平等问题以及正在开发的替代治疗策略，旨在为所有pwCF获得有效的治疗方法。
