Rapid Improvement after Starting Elexacaftor-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease

被引：167

作者：

Burgel, Pierre-Regis ^{[1
,2
,3
]}

Durieu, Isabelle ^{[3
,4
,5
]}

Chiron, Raphael ^{[6
]}

Ramel, Sophie ^{[7
]}

Danner-Boucher, Isabelle ^{[8
]}

Prevotat, Anne ^{[9
]}

Grenet, Dominique ^{[10
]}

Marguet, Christophe ^{[11
]}

Reynaud-Gaubert, Martine ^{[12
]}

Macey, Julie ^{[13
]}

Mely, Laurent ^{[14
]}

Fenton, Annlyse ^{[15
]}

Quetant, Sebastien ^{[16
]}

Lemonnier, Lydie ^{[17
]}

Paillasseur, Jean-Louis ^{[18
]}

Da Silva, Jennifer ^{[1
,3
,19
]}

Martin, Clemence ^{[1
,2
,3
]}

机构：

[1] Univ Paris, Inst Cochin, INSERM, Unite 1016, Paris, France

[2] Cochin Hosp, AP HP, Resp Med & Cyst Fibrosis Natl Reference Ctr, Paris, France

[3] European Reference Network Rare Resp Dis, Cyst Fibrosis Network, Frankfurt, Germany

[4] Hosp Civils Lyon, Ctr Reference Adulte Mucoviscidose, Serv Med Interne, Pierre Benite, France

[5] Univ Lyon, Serv Sante & Rech Rendement, Equipe Accueil 7425, Lyon, France

[6] Ctr Hosp Univ Montpellier, Ctr Mucoviscidose, Hop Arnaud de Villeneuve, Montpellier, France

[7] Fdn Ildys, Ctr Ressources & Competences Mucoviscidose, Roscoff, France

[8] CHU Nantes, Inst Thorax, Serv Pneumol, Nantes, France

[9] Univ Lille, CHU Lille, Ctr Mucoviscidose, Serv Pneumol & Immunoallergol,Hop Calmette, Lille, France

[10] Hop Foch, Serv Pneumol, Suresnes, France

[11] Univ Rouen Normandie, Hosp Univ Rouen Normandie, Ctr Malad Resp Pediat & Mucoviscidose, INSERM,Equipe Accueil 2656, Rouen, France

[12] Aix Marseille Univ, Nord Hosp, AP HM, Dept Resp Med & Lung Transplantat, Marseille, France

[13] Univ Hosp Ctr Bordeaux, Resp Med & Cyst Fibrosis Ctr, Bordeaux, France

[14] Renee Sabran Hosp, Cyst Fibrosis Ctr, Giens, France

[15] Dijon Univ Hosp, Cyst Fibrosis Resource & Competence Ctr Adults, Dept Pulm Med, Dijon, France

[16] Ctr Hosp Univ Grenoble Alpes, Serv Hosp Univ Pneumol & Physiol, Pole Thorax & Vaisseaux, La Tronche, France

[17] Assoc Vaincre Mucoviscidose, Paris, France

[18] Effi Stat, Paris, France

[19] Hop Cochin, AP HP, Unite Rech Clin, Ctr Invest Clin Paris Descartes Necker Cochin, Paris, France

来源：

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE | 2021年 / 204卷 / 01期

关键词：

cystic fibrosis transmembrane conductance regulator modulators; elexacaftor; lung transplantation;

D O I：

10.1164/rccm.202011-4153OC

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

Rationale: 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. Objectives: To evaluate the effects of elexacaftor-tezacaftor-ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged >12 years and with a percent-predicted FEV1 (ppFEV1),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. Measurements and Main Results: Elexacaftor-tezacaftor-ivacaftor was initiated in 245 patients with a median (interquartile range) ppFEV(1) = 29 (24-34). The mean (95% confidence interval) absolute increase in the ppFEV(1) was 115.1 (113.8 to 116.4; P < 0.0001), and the mean (95% confidence interval) in weight was +4.2 kg (+3.9 to +4.6; P < 0.0001). The number of patients requiring long-term oxygen, noninvasive ventilation, and/or enteral tube feeding decreased by 50%, 30%, and 50%, respectively (P < 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. Conclusions: In patients with advanced disease, elexacaftor-tezacaftor-ivacaftor is associated with rapid clinical improvement, often leading to the indication for lung transplantation being suspended.

引用

页码：64 / 73

页数：10

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