Université de Paris, Institut Cochin, Unité 1016, Institut National de la Santé et de la Recherche Médicale, Paris, France.
Respiratory Medicine and Cystic Fibrosis National Reference Center, Cochin Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
Am J Respir Crit Care Med. 2021 Jul 1;204(1):64-73. doi: 10.1164/rccm.202011-4153OC.
Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV (ppFEV) <40 who initiated elexacaftor-tezacaftor-ivacaftor from December 2019 to August 2020 in France was conducted. Clinical characteristics were collected at initiation and at 1 and 3 months. Safety and effectiveness were evaluated by September 2020. National-level transplantation and mortality figures for 2020 were obtained from the French CF and transplant centers and registries. Elexacaftor-tezacaftor- ivacaftor was initiated in 245 patients with a median (interquartile range) ppFEV = 29 (24-34). The mean (95% confidence interval) absolute increase in the ppFEV was +15.1 (+13.8 to +16.4; < 0.0001), and the mean (95% confidence interval) in weight was +4.2 kg (+3.9 to +4.6; < 0.0001). The number of patients requiring long-term oxygen, noninvasive ventilation, and/or enteral tube feeding decreased by 50%, 30%, and 50%, respectively ( < 0.01). Although 16 patients were on the transplant waiting list and 37 were undergoing transplantation evaluation at treatment initiation, only 2 received a transplant, and 1 died. By September 2020, only five patients were still on the transplantation path. Compared with the previous 2 years, a twofold decrease in the number of lung transplantations in patients with CF was observed in 2020, whereas the number of deaths without transplantation remained stable. In patients with advanced disease, elexacaftor-tezacaftor-ivacaftor is associated with rapid clinical improvement, often leading to the indication for lung transplantation being suspended.
依伐卡托与泰比卡托与埃他卡托三联组合是一种 CFTR（囊性纤维化跨膜电导调节因子）调节剂，适用于至少有一个 Phe508del 突变的 CF 患者。 评估依伐卡托与泰比卡托与埃他卡托三联组合在患有晚期呼吸疾病的 CF 患者中的效果。 进行了一项前瞻性观察研究，纳入了 2019 年 12 月至 2020 年 8 月期间在法国开始接受依伐卡托与泰比卡托与埃他卡托三联组合治疗的所有年龄 ⩾12 岁且预计 FEV（ppFEV）<40%的患者。在起始时和 1 个月及 3 个月时采集临床特征。安全性和有效性评估截至 2020 年 9 月。2020 年的全国移植和死亡率数据来自法国 CF 和移植中心以及登记处。 245 例患者开始接受依伐卡托与泰比卡托与埃他卡托三联组合治疗，中位（四分位距）ppFEV=29（24-34）。ppFEV 的平均（95%置信区间）绝对值增加了+15.1（+13.8 至 +16.4；<0.0001），体重的平均（95%置信区间）增加了+4.2 公斤（+3.9 至 +4.6；<0.0001）。需要长期吸氧、无创通气和/或肠内管饲的患者数量分别减少了 50%、30%和 50%（<0.01）。尽管治疗开始时有 16 例患者在移植等待名单上，37 例患者正在接受移植评估，但仅 2 例接受了移植，1 例死亡。截至 2020 年 9 月，仅有 5 例患者仍在移植途径上。与前两年相比，2020 年 CF 患者的肺移植数量减少了一倍，而无移植的死亡人数保持稳定。 在患有晚期疾病的患者中，依伐卡托与泰比卡托与埃他卡托三联组合与快速临床改善相关，通常导致暂停肺移植的指征。
