Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Patients with Cystic Fibrosis and One or Two F508del Alleles

被引：76

作者：

Graeber, Simon Y. ^{[1
,2
,6
,7
]}

Renz, Diane M. ^{[8
]}

Stahl, Mirjam ^{[1
,2
,6
,7
]}

Pallenberg, Sophia T. ^{[9
,10
]}

Sommerburg, Olaf ^{[13
,14
,15
]}

Naehrlich, Lutz ^{[17
,18
]}

Berges, Julian ^{[13
,14
,15
]}

Dohna, Martha ^{[8
]}

Ringshausen, Felix C. ^{[10
,11
]}

Doellinger, Felix ^{[3
,4
,5
]}

Vitzthum, Constanze ^{[1
,2
,7
]}

Roehmel, Jobst ^{[1
,2
,7
]}

Allomba, Christine ^{[1
,2
,7
]}

Haemmerling, Susanne ^{[13
,14
]}

Barth, Sandra ^{[17
,18
]}

Rueckes-Nilges, Claudia ^{[17
,18
]}

Wielpuetz, Mark O. ^{[15
,16
]}

Hansen, Gesine ^{[9
,10
,12
]}

Vogel-Claussen, Jens ^{[8
,9
]}

Tuemmler, Burkhard ^{[9
,10
]}

Mall, Marcus A. ^{[1
,2
,6
,7
]}

Dittrich, Anna-Maria ^{[9
,10
]}

机构：

[1] Charite Univ Med Berlin, Dept Pediat Resp Med Immunol & Crit Care Med, Augustenburger Pl 1, D-13353 Berlin, Germany

[2] Charite Univ Med Berlin, Cyst Fibrosis Ctr, Berlin, Germany

[3] Charite Univ Med Berlin, Dept Radiol, Berlin, Germany

[4] Free Univ Berlin, Berlin, Germany

[5] Humboldt Univ, Berlin, Germany

[6] Charite Univ Med Berlin, Berlin Inst Hlth, Berlin, Germany

[7] German Ctr Lung Res DZL, Associated Partner Site, Berlin, Germany

[8] Hannover Med Sch, Dept Radiol, Hannover, Germany

[9] Hannover Med Sch, Dept Pediat Pneumol Allergol & Neonatol, Hannover, Germany

[10] Hannover Med Sch, German Ctr Lung Res Biomed Res Endstage & Obstruc, Hannover, Germany

[11] Hannover Med Sch, Dept Pneumol, Hannover, Germany

[12] Hannover Med Sch, Cluster Excellence RESIST EXC 2155, German Res Fdn DFG, Hannover, Germany

[13] Heidelberg Univ, Div Pediat Pulmonol & Allergy, Heidelberg, Germany

[14] Heidelberg Univ, Cyst Fibrosis Ctr, Dept Pediat, Heidelberg, Germany

[15] Heidelberg Univ, Dept Translat Pulmonol, Translat Lung Res Ctr Heidelberg TLRC, German Ctr Lung Res DZL, Heidelberg, Germany

[16] Heidelberg Univ, Dept Diagnost & Intervent Radiol, Heidelberg, Germany

[17] Justus Liebig Univ Giessen, Dept Pediat, Giessen, Germany

[18] German Ctr Lung Res DZL, Univ Giessen & Marburg Lung Ctr UGMLC, Giessen, Germany

来源：

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE | 2022年 / 206卷 / 03期

关键词：

CFTR modulator therapy; cystic fibrosis; magnetic resonance imaging; multiple-breath washout; elexacaftor/tezacaftor/ivacaftor; TEZACAFTOR-IVACAFTOR; LUMACAFTOR-IVACAFTOR; PRESCHOOL-CHILDREN; DISEASE; EFFICACY; MUTATION; SAFETY; CF; VENTILATION; PROGRESSION;

D O I：

10.1164/rccm.202201-0219OC

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

Rationale: We recently demonstrated that triple-combination CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves CFTR function in airway and intestinal epithelia to 40-50% of normal in patients with cystic fibrosis (CF) with one or two F508del alleles. In previous studies, this improvement of CFTR function was shown to improve clinical outcomes; however, effects on the lung clearance index (LCI) determined by multiple-breath washout and abnormalities in lung morphology and perfusion detected by magnetic resonance imaging (MRI) have not been studied. Objectives: To examine the effect of ELX/TEZ/IVA on LCI and lung MRI scores in patients with CF and one or two F508del alleles aged >= 12 years. Methods: This prospective, observational, multicenter, postapproval study assessed LCI and lung MRI scores before and 8-16 weeks after initiation of ELX/TEZ/IVA. Measurements and Main Results: A total of 91 patients with CF, including 45 heterozygous for F508del and a minimal function mutation (MF) and 46 homozygous for F508del, were enrolled in this study. Treatment with ELX/TEZ/IVA improved LCI in F508del/MF (22.4; interquartile range [IQR], 23.7 to 21.1; P < 0.001) and F508del homozygous (21.4; IQR, 22.4 to 20.4; P < 0.001) patients. Furthermore, ELX/TEZ/IVA improved the MRI global score in F508del/MF (26.0; IQR, 211.0 to 21.3; P < 0.001) and F508del homozygous (26.5; IQR, 211.0 to 21.3; P < 0.001) patients. Conclusions: Our data demonstrate that improvement of CFTR function by ELX/TEZ/IVA improves lung ventilation and abnormalities in lung morphology, including airway mucus plugging and wall thickening, in adolescent and adult patients with CF and one or two F508del alleles in a real-world, postapproval setting.

引用

页码：311 / 320

页数：10

共 52 条

[51] Correction of sensor crosstalk error in Exhalyzer D multiple-breath washout device significantly impacts outcomes in children with cystic fibrosis [J].

Wyler, Florian ;

Oestreich, Marc-Alexander ;

Frauchiger, Bettina S. ;

Ramsey, Kathryn A. ;

Latzin, Philipp .

JOURNAL OF APPLIED PHYSIOLOGY, 2021, 131 (03) :1148-1156

[52] A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/lvacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One F508del Allele [J].

Zemanick, Edith T. ;

Taylor-Cousar, Jennifer L. ;

Davies, Jane ;

Gibson, Ronald L. ;

Mall, Marcus A. ;

McKone, Edward F. ;

McNally, Paul ;

Ramsey, Bonnie W. ;

Rayment, Jonathan H. ;

Rowe, Steven M. ;

Tullis, Elizabeth ;

Ahluwalia, Neil ;

Chu, Chenghao ;

Ho, Thang ;

Moskowitz, Samuel M. ;

Noel, Sabrina ;

Tian, Simon ;

Waltz, David ;

Weinstock, Tanya G. ;

Xuan, Fengjuan ;

Wainwright, Claire E. ;

McColley, Susanna A. .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2021, 203 (12) :1522-1532

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