French Cystic Fibrosis National Reference Center, Department of Respiratory Medicine, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France.
Institut Cochin, Université de Paris Cité, INSERM U1016, 75014 Paris, France.
Cells. 2022 May 28;11(11):1769. doi: 10.3390/cells11111769.
Cystic fibrosis (CF) is a rare genetic multisystemic disease, the manifestations of which are due to mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein and can lead to respiratory insufficiency and premature death. CFTR modulators, which were developed in the past decade, partially restore CFTR protein function. Their clinical efficacy has been demonstrated in phase 3 clinical trials, particularly in terms of lung function and pulmonary exacerbations, nutritional status, and quality of life in people with gating mutations (ivacaftor), homozygous for the F508del mutation (lumacaftor/ivacaftor and tezacaftor/ivacaftor), and in those with at least one F508del mutation (elexacaftor/tezacaftor/ivacaftor). However, many questions remain regarding their long-term safety and effectiveness, particularly in patients with advanced lung disease, liver disease, renal insufficiency, or problematic bacterial colonization. The impact of CFTR modulators on other important outcomes such as concurrent treatments, lung transplantation, chest imaging, or pregnancies also warrants further investigation. The French CF Reference Network includes 47 CF centers that contribute patient data to the comprehensive French CF Registry and have conducted nationwide real-world studies on CFTR modulators. This review seeks to summarize the results of these real-world studies and examine their findings against those of randomized control trials.
囊性纤维化（CF）是一种罕见的遗传性多系统疾病，其临床表现归因于编码 CF 跨膜电导调节蛋白（CFTR）的基因突变，并可导致呼吸功能不全和过早死亡。过去十年开发的 CFTR 调节剂部分恢复了 CFTR 蛋白的功能。它们的临床疗效已在 3 期临床试验中得到证实，特别是在有门控突变（ivacaftor）、纯合 F508del 突变（lumacaftor/ivacaftor 和 tezacaftor/ivacaftor）和至少有一个 F508del 突变的人群中，在肺功能和肺部恶化、营养状况和生活质量方面。然而，关于它们的长期安全性和有效性仍存在许多问题，特别是在患有晚期肺病、肝病、肾功能不全或存在细菌定植问题的患者中。CFTR 调节剂对其他重要结局（如同时进行的治疗、肺移植、胸部成像或妊娠）的影响也需要进一步研究。法国 CF 参考网络包括 47 个 CF 中心，这些中心向全面的法国 CF 登记处提供患者数据，并对 CFTR 调节剂进行了全国范围的真实世界研究。这篇综述旨在总结这些真实世界研究的结果，并将其发现与随机对照试验的结果进行比较。
