TY - JOUR
T1 - Clinical Effectiveness of Lumacaftor/Ivacaftor in Patients with Cystic Fibrosis Homozygous for F508del-CFTR A Clinical Trial
AU - on behalf of the PROSPECT Investigators of the Cystic Fibrosis Foundation Therapeutics Development Network
AU - Sagel, Scott D.
AU - Khan, Umer
AU - Heltshe, Sonya L.
AU - Clancy, John P.
AU - Borowitz, Drucy
AU - Gelfond, Daniel
AU - Donaldson, Scott H.
AU - Moran, Antoinette
AU - Ratjen, Felix
AU - VanDalfsen, Jill M.
AU - Rowe, Steven M.
N1 - Publisher Copyright:
Copyright © 2021 by the American Thoracic Society
PY - 2021/1
Y1 - 2021/1
N2 - Rationale: The combination of lumacaftor (LUM) and ivacaftor (IVA) is an approved CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator treatment for homozygous F508del patients with CF. Objectives: To evaluate the effectiveness of LUM/IVA in children (6 yr or more) and adults (more than 18 yr) in a postapproval setting. Methods: This longitudinal cohort study, performed at 38 centers in the U.S. CF Therapeutics Development Network, enrolled homozygous F508del patients with CF ages 6 years old and older with no prior exposure to LUM/IVA. Study assessments were performed at baseline and at 1, 3, 6, and 12 months after LUM/IVA initiation. Results: A total of 193 patients initiated LUM/IVA, and 85% completed the study through 1 year. Baseline mean percent-predicted forced expiratory volume in 1 second (ppFEV1) was 85 (standard deviation, 22.4) in this cohort. No statistically significant change in ppFEV1 was observed from baseline to any of the followup time points, with a mean absolute change at 12 months of 20.3 (95% confidence interval [CI], 21.8 to 1.2). Body mass index improved from baseline to 12 months (mean change, 0.8 kg/m2; P, 0.001). Sweat chloride decreased from baseline to 1 month (mean change, 218.5 mmol/L; 95% CI, 220.7 to 216.3; P, 0.001), and these reductions were sustained through the study period. There were no significant changes in hospitalization rate for pulmonary exacerbations and Pseudomonas aeruginosa infection status with treatment. Conclusions: In this real-world multicenter cohort of children and adults, LUM/IVA treatment was associated with significant improvements in growth and reductions in sweat chloride without statistically significant or clinically meaningful changes in lung function, hospitalization rates, or P. aeruginosa infection. Clinical trial registered with www.clinicaltrials.gov (NCT 02477319).
AB - Rationale: The combination of lumacaftor (LUM) and ivacaftor (IVA) is an approved CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator treatment for homozygous F508del patients with CF. Objectives: To evaluate the effectiveness of LUM/IVA in children (6 yr or more) and adults (more than 18 yr) in a postapproval setting. Methods: This longitudinal cohort study, performed at 38 centers in the U.S. CF Therapeutics Development Network, enrolled homozygous F508del patients with CF ages 6 years old and older with no prior exposure to LUM/IVA. Study assessments were performed at baseline and at 1, 3, 6, and 12 months after LUM/IVA initiation. Results: A total of 193 patients initiated LUM/IVA, and 85% completed the study through 1 year. Baseline mean percent-predicted forced expiratory volume in 1 second (ppFEV1) was 85 (standard deviation, 22.4) in this cohort. No statistically significant change in ppFEV1 was observed from baseline to any of the followup time points, with a mean absolute change at 12 months of 20.3 (95% confidence interval [CI], 21.8 to 1.2). Body mass index improved from baseline to 12 months (mean change, 0.8 kg/m2; P, 0.001). Sweat chloride decreased from baseline to 1 month (mean change, 218.5 mmol/L; 95% CI, 220.7 to 216.3; P, 0.001), and these reductions were sustained through the study period. There were no significant changes in hospitalization rate for pulmonary exacerbations and Pseudomonas aeruginosa infection status with treatment. Conclusions: In this real-world multicenter cohort of children and adults, LUM/IVA treatment was associated with significant improvements in growth and reductions in sweat chloride without statistically significant or clinically meaningful changes in lung function, hospitalization rates, or P. aeruginosa infection. Clinical trial registered with www.clinicaltrials.gov (NCT 02477319).
KW - Clinical effectiveness
KW - Cystic fibrosis
KW - Ivacaftor
KW - Lumacaftor
KW - Postapproval study
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U2 - 10.1513/AnnalsATS.202002-144OC
DO - 10.1513/AnnalsATS.202002-144OC
M3 - Article
C2 - 32644818
AN - SCOPUS:85098733547
SN - 2329-6933
VL - 18
SP - 75
EP - 83
JO - Annals of the American Thoracic Society
JF - Annals of the American Thoracic Society
IS - 1
ER -