TY - JOUR
T1 - Real-life efficacy and safety of elexacaftor/tezacaftor/ivacaftor on severe cystic fibrosis lung disease patients
AU - Kos, Renate
AU - Neerincx, Anne H.
AU - Fenn, Dominic W.
AU - Brinkman, Paul
AU - Lub, Rianne
AU - Vonk, Steffie E. M.
AU - Roukema, Jolt
AU - Reijers, Monique H.
AU - Terheggen-Lagro, Suzanne W. J.
AU - Altenburg, Josje
AU - Majoor, Christof J.
AU - Amsterdam Mucociliary Clearance Disease (AMCD) research group
AU - Bos, Lieuwe D.
AU - Haarman, Eric G.
AU - Maitland-van der Zee, Anke H.
N1 - Funding Information: PB has received research grants outside the submitted work from the Amsterdam UMC, Stichting Astma Bestrijding (SAB), Boehringer Íngelheim, and Vertex. JR has received a personal fee outside of the submitted work from the Vertex pharmaceuticals for giving a lecture/webinar. AHM has received research grants outside the submitted work from GSK, Boehringer Íngelheim, and Vertex, she is the PI of a P4O2 (Precision Medicine for more Oxygen) public–private partnership sponsored by Health Holland involving many private partners that contribute in cash and/or in kind (Boehringer Ingelheim, Breathomix, Fluidda, Ortec Logiqcare, Philips, Quantib‐U, Roche, Smartfish, SODAQ, Thirona, TopMD, and Novartis), and she has served in advisory boards for AstraZeneca, GSK, and Boehringer Ingelheim with money paid to her institution. Funding Information: The authors acknowledge and thank all patients and parents as well as J.W.F. Dagelet, M. van Brederode, and L. van der Schaaf of the Amsterdam UMC and E. Erren and E. Gerritsen of the Radboud UMC for their time and support to this study. Publisher Copyright: © 2022 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Elexacaftor/tezacaftor/ivacaftor (ETI) is a cystic fibrosis (CF) transmembrane conductance regulator modulator, which has shown efficacy in CF patients (≥6 years) with ≥1 Phe508del mutation and a minimal function mutation. In October 2019, ETI became available on compassionate use basis for Dutch CF patients with severe lung disease. Our objective was to investigate safety and efficacy of ETI in this patient group in a real-life setting. A multicenter longitudinal observational study was conducted to examine changes in FEV1, BMI, and adverse events at initiation and 1, 3, 6, and 12 months after starting ETI. The number of exacerbations was recorded in the 12 months before and the 12 months after ETI treatment. Patients eligible for compassionate use had a FEV1 <40% predicted. Wilcoxon signed-rank test analyzed changes over time. Twenty subjects were included and followed up for up to 12 months after starting ETI. Treatment was well tolerated with mild side effects reported, namely, rash (15%) and stomach ache (20%) with 80% resolving within 1 month. Mean absolute increase of FEV1 was 11.8/13.7% (p ≤.001) and BMI was 0.49/1.87 kg/m2 (p <.001–0.02) after 1/12 months, respectively. In comparison to the number of exacerbations pretrial, there was a marked reduction in exacerbations after initiation. Our findings show long-term effects of treatment with ETI in patients with severe CF lung disease in a real-life setting. Treatment with ETI is associated with increased lung function and BMI, less exacerbations, and only mild side effects.
AB - Elexacaftor/tezacaftor/ivacaftor (ETI) is a cystic fibrosis (CF) transmembrane conductance regulator modulator, which has shown efficacy in CF patients (≥6 years) with ≥1 Phe508del mutation and a minimal function mutation. In October 2019, ETI became available on compassionate use basis for Dutch CF patients with severe lung disease. Our objective was to investigate safety and efficacy of ETI in this patient group in a real-life setting. A multicenter longitudinal observational study was conducted to examine changes in FEV1, BMI, and adverse events at initiation and 1, 3, 6, and 12 months after starting ETI. The number of exacerbations was recorded in the 12 months before and the 12 months after ETI treatment. Patients eligible for compassionate use had a FEV1 <40% predicted. Wilcoxon signed-rank test analyzed changes over time. Twenty subjects were included and followed up for up to 12 months after starting ETI. Treatment was well tolerated with mild side effects reported, namely, rash (15%) and stomach ache (20%) with 80% resolving within 1 month. Mean absolute increase of FEV1 was 11.8/13.7% (p ≤.001) and BMI was 0.49/1.87 kg/m2 (p <.001–0.02) after 1/12 months, respectively. In comparison to the number of exacerbations pretrial, there was a marked reduction in exacerbations after initiation. Our findings show long-term effects of treatment with ETI in patients with severe CF lung disease in a real-life setting. Treatment with ETI is associated with increased lung function and BMI, less exacerbations, and only mild side effects.
KW - cystic fibrosis
KW - elexacaftor/tezacaftor/ivacaftor
KW - modulators
KW - sputum
UR - http://www.scopus.com/inward/record.url?scp=85142777401&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/prp2.1015
DO - https://doi.org/10.1002/prp2.1015
M3 - Article
C2 - 36440690
SN - 2052-1707
VL - 10
SP - e01015
JO - Pharmacology research & perspectives
JF - Pharmacology research & perspectives
IS - 6
M1 - e01015
ER -