TY - JOUR
T1 - Radiological and long-term clinical response to elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with advanced lung disease
AU - Aalbers, Bente L.
AU - Mohamed Hoesein, Firdaus A.A.
AU - Hofland, Regina W.
AU - Bronsveld, Inez
AU - Kruijswijk, Marian A.
AU - Schotman, Suzan
AU - Slingerland, Corlien W.
AU - Panhuis, Hannah
AU - van der Ent, C. Kors
AU - Heijerman, Harry G.M.
N1 - Funding Information:
Harry G. M. Heijerman has provided assistance to Vertex pharmaceuticals, the manufacturer of lumacaftor/ivacaftor, as member of the advisory board, speaker, and investigator in clinical studies. Bente L. Aalbers has assisted in clinical trials for Vertex as a sub‐investigator. CK van der Ent reports grants from Vertex, outside the submitted work.
Publisher Copyright:
© 2023 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.
PY - 2023/8
Y1 - 2023/8
N2 - Introduction: A triple combination of CFTR modulators ELE/TEZ/IVA (elexacaftor/tezacaftor/ivacaftor, Trikafta™) has been evaluated in clinical trials for people with cystic fibrosis (pwCF) and was approved to the European and US market. During registration and settling reimbursement in Europe, it could be requested on a compassionate use basis, for patients with advanced lung disease (ppFEV1 < 40). Aim: The aim of this study is to evaluate 2 years of experience with the clinical and radiological response of ELE/TEZ/IVA in pwCF in a compassionate use setting. Methods: pwCF who started ELE/TEZ/IVA in a compassionate use setting were prospectively followed with assessment of spirometry, BMI, chest CT, CFQ-R and sweat chloride concentration (SCC) before start and after 3 months. Furthermore, spirometry, sputum cultures, and BMI were repeated after 1, 6, 12, 18, and 24 months. Results: Eighteen patients were eligible for this evaluation, nine with F508del/F508del genotype (eight of whom were using dual CFTR modulators) and nine with F508del/minimal function mutation. After 3 months, mean change in SCC was −44.9 (p ≤ 0.001), together with significant improvement in CT (change in Brody score: −28.27 p ≤ 0.001) and CFQ-R results (change in respiratory domain: +18.8, p = 0.002). After 24 months, ppFEV1 change was +8.89 (p = 0.002), BMI had improved by +1.53 kg/m2 (p ≤ 0.001) and exacerbation rate declined from 5.94 in 24 months before start to 1.17 (p ≤ 0.001) in the 24 months after. Conclusion: pwCF with advanced lung disease experience relevant clinical benefit after 2 years of treatment with ELE/TEZ/IVA in a compassionate use setting. Structural lung damage, quality of life, exacerbation rate, and BMI improved significantly with treatment. Gain in ppFEV1 is lower compared to the phase III trials that included younger patients with moderately affected lung function.
AB - Introduction: A triple combination of CFTR modulators ELE/TEZ/IVA (elexacaftor/tezacaftor/ivacaftor, Trikafta™) has been evaluated in clinical trials for people with cystic fibrosis (pwCF) and was approved to the European and US market. During registration and settling reimbursement in Europe, it could be requested on a compassionate use basis, for patients with advanced lung disease (ppFEV1 < 40). Aim: The aim of this study is to evaluate 2 years of experience with the clinical and radiological response of ELE/TEZ/IVA in pwCF in a compassionate use setting. Methods: pwCF who started ELE/TEZ/IVA in a compassionate use setting were prospectively followed with assessment of spirometry, BMI, chest CT, CFQ-R and sweat chloride concentration (SCC) before start and after 3 months. Furthermore, spirometry, sputum cultures, and BMI were repeated after 1, 6, 12, 18, and 24 months. Results: Eighteen patients were eligible for this evaluation, nine with F508del/F508del genotype (eight of whom were using dual CFTR modulators) and nine with F508del/minimal function mutation. After 3 months, mean change in SCC was −44.9 (p ≤ 0.001), together with significant improvement in CT (change in Brody score: −28.27 p ≤ 0.001) and CFQ-R results (change in respiratory domain: +18.8, p = 0.002). After 24 months, ppFEV1 change was +8.89 (p = 0.002), BMI had improved by +1.53 kg/m2 (p ≤ 0.001) and exacerbation rate declined from 5.94 in 24 months before start to 1.17 (p ≤ 0.001) in the 24 months after. Conclusion: pwCF with advanced lung disease experience relevant clinical benefit after 2 years of treatment with ELE/TEZ/IVA in a compassionate use setting. Structural lung damage, quality of life, exacerbation rate, and BMI improved significantly with treatment. Gain in ppFEV1 is lower compared to the phase III trials that included younger patients with moderately affected lung function.
KW - Brody score
KW - CFTR modulators
KW - chest CT
KW - cystic fibrosis
KW - quality of life
UR - https://www.scopus.com/pages/publications/85160104597
U2 - 10.1002/ppul.26486
DO - 10.1002/ppul.26486
M3 - Article
C2 - 37222401
SN - 8755-6863
VL - 58
SP - 2317
EP - 2322
JO - Pediatric Pulmonology
JF - Pediatric Pulmonology
IS - 8
ER -