Multisystemic Effects of Elexacaftor-Tezacaftor-Ivacaftor in Adults with Cystic Fibrosis and Advanced Lung Disease

被引：17

作者：

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

Paillasseur, Jean-Louis ^{[4
]}

Durieu, Isabelle ^{[5
,6
]}

Reynaud-Gaubert, Martine ^{[7
]}

Hamidfar, Rebecca ^{[8
]}

Murris-Espin, Marlene ^{[9
]}

Danner-Boucher, Isabelle ^{[10
]}

Chiron, Raphael ^{[11
]}

Leroy, Sylvie ^{[12
]}

Douvry, Benoit ^{[13
]}

Grenet, Dominique ^{[14
]}

Mely, Laurent ^{[15
]}

Ramel, Sophie ^{[16
]}

Montcouquiol, Sylvie ^{[17
]}

Burnet, Esperie ^{[2
,3
]}

Ouaalaya, El Hassane ^{[4
]}

Sogni, Philippe ^{[18
,19
]}

Da Silva, Jennifer ^{[2
,3
]}

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

机构：

[1] Univ Paris Cite, Inst Cochin, INSERM, U1016, Paris, France

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

[3] ERN Lung CF Network, Frankfurt, Germany

[4] Effi Stat, Paris, France

[5] Hosp Civils Lyon, Serv M ed Interne, Ctr Reference Adulte Mucoviscidose, Pierre Benite, France

[6] Univ Lyon, INSERM, U1290, Lab Rech Sante Publ RESHAPE, Lyon, France

[7] Aix Marseille Univ, Hop Nord, Assistance Publ Hop Marseille, Dept Resp Med & Lung Transplantat,Adult Cystic Fi, Marseille, France

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

[9] CHU Toulouse, Hop Larrey, Ctr Ressources & Competences Mucoviscidose, Serv Pneumol,Pole Voies Resp, Toulouse, France

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

[11] Ctr Hosp Univ Montpellier, Hop Arnaud de Villeneuve, Ctr Ressources & Competences Mucoviscidose, Montpellier, France

[12] Univ Cote Azur, Serv Pneumol, Ctr Hosp Univ Nice, Federat Hospitalouniv OncoAge,CNRS,INSERM,Inst Re, Nice, France

[13] Ctr Hosp Intercommunal, FHU SENEC, Serv Pneumol, Creteil, France

[14] Hop Foch, Serv Pneumol, Ctr Ressources & Comp etences Mucoviscidose, Ctr Transplantat Pulm, Suresnes, France

[15] Hop Renee Sabran, Ctr Ressources & Competences Mucoviscidose, Giens, France

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

[17] CHU Clermont Ferrand, Ctr Ressources & Competences Mucoviscidose, Clermont Ferrand, France

[18] Cochin Hosp, Liver Unit, Paris, France

[19] Paris Cite Univ, AP HP, Paris, France

来源：

ANNALS OF THE AMERICAN THORACIC SOCIETY | 2024年 / 21卷 / 07期

关键词：

real-word evidence; cystic fibrosis transmembrane onductance regulator modulators; severe cystic fibrosis liver disease; TRANSPLANT CANDIDATES; ELEXACAFTOR/TEZACAFTOR/IVACAFTOR; UPDATE;

D O I：

10.1513/AnnalsATS.202312-1065OC

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

Rationale: Limited data exist on the safety and effectiveness of elexacaftor-tezacaftor-ivacaftor (ETI) in people with cystic fibrosis (pwCF) and advanced lung disease. Objectives: To evaluate the effects of ETI in an unselected population of pwCF and advanced lung disease. Methods: A prospective observational study, including all adults aged 18 years and older with percentage predicted forced expiratory volume in 1 second (ppFEV(1))<= 40 who initiated ETI from December 2019 to June 2021 in France, was conducted. PwCF were followed until August 8, 2022. Results: ETI was initiated in 434 pwCF with a median ppFEV(1) of 30 (interquartile range, 25-35), including 27 with severe cystic fibrosis liver disease and 183 with diabetes. PwCF were followed for a median of 587 (interquartile range, 396-728) days after ETI initiation. Discontinuation of ETI occurred in 12 (2.8%) pwCF and was due mostly to lung transplantation (n = 5) or death (n = 4). Absolute increase in ppFEV(1) by a mean of 114.2% (95% confidence interval, 13.1-15.4%) occurred at 1 month and persisted throughout the study. Increase in ppFEV(1) in the youngest age quartile was almost twice that of the oldest quartile (P < 0.001); body mass index, 18.5 kg/m(2) was found in 38.6% at initiation versus 11.3% at 12 months (P = 0.0001). Increases in serum concentrations of vitamins A and E, but not 25-hydroxy vitamin D-3, were observed. Significant reductions in the percentages of pwCF using oxygen therapy, noninvasive ventilation, nutritional support, and inhaled and systemic therapies (including antibiotics) were observed; insulin was discontinued in 12% of patients with diabetes. Conclusions: ETI is safe in pwCF and advanced lung disease, with multisystem pulmonary and extrapulmonary benefits.

引用

页码：1053 / 1064

页数：12

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