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. 2022 Feb 16;11(4):1021.
doi: 10.3390/jcm11041021.

Elexacaftor/Tezacaftor/Ivacaftor in Patients with Cystic Fibrosis Homozygous for the F508del Mutation and Advanced Lung Disease: A 48-Week Observational Study

Vincenzo Carnovale  1 , Paola Iacotucci  1 , Vito Terlizzi  2 , Carmela Colangelo  3 , Lorenza Ferrillo  1 , Angela Pepe  3   4 , Michela Francalanci  2 , Giovanni Taccetti  2 , Serena Buonaurio  1 , Assunta Celardo  1 , Laura Salvadori  1 , Giovanni Marsicovetere  3 , Michele D'Andria  3 , Nicola Ferrara  1 , Donatello Salvatore  3
Affiliations

Elexacaftor/Tezacaftor/Ivacaftor in Patients with Cystic Fibrosis Homozygous for the F508del Mutation and Advanced Lung Disease: A 48-Week Observational Study

Vincenzo Carnovale et al. J Clin Med. .

Abstract

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) is the newest cystic fibrosis transmembrane conductance regulator (CFTR) modulator drug approved for the treatment of patients with cystic fibrosis (pwCF) aged ≥6 years with at least one copy of the F508del mutation (F) in the CFTR gene or another mutation that is responsive to treatment with ETI. This study determined the effectiveness and safety of ETI in a cohort of severely affected pwCF with an F/F genotype.

Methods: Retrospective observational study in F/F pwCF treated for 48 weeks, enrolled in an ETI managed access program available to subjects with advanced lung disease (ppFEV1 < 40). Twenty-six patients from three centres were included. The main outcomes included lung function, sweat chloride concentration (SCC), nutrition, frequency of pulmonary exacerbations (PEx), CFQ-R, and safety.

Results: ppFEV1 improved by 12.06 (95%CI 8.54, 15.57) from baseline after 4 weeks of treatment with ETI, 15.32 (11.3, 19.34) after 24 weeks, and 14.48 (10.64, 18.32) after 48 weeks. The increase in FEV1 was accompanied by a decrease in SCC, improvement of BMI, and noticeable reduction in PEx. An overall good safety profile was observed.

Conclusions: In F/F pwCF with advanced lung disease with an F/F genotype, ETI was safe and associated with clinical improvement.

Keywords: advanced lung disease; cystic fibrosis; elexacaftor/tezacaftor/ivacaftor.

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Conflict of interest statement

D.S. has been principal investigator in several clinical trials conducted by Vertex Pharmaceuticals and for which his institution has received funding; he has received fees for participation in advisory boards, satellite symposia, or specific projects. V.C. and PI have received fees for participation in advisory boards and consultancy from Vertex Pharmaceuticals. C.C., G.M. and M.D. report supported attendance at meetings and travel from Vertex Pharmaceuticals. V.T., L.F., M.F., A.P., S.B., A.C., L.S. and N.F. have nothing to disclose.

Figures

Figure 1
Figure 1
Effect of treatment with elexacaftor/tezacaftor/ivacaftor on percentage of predicted FEV1 from baseline through to week 48. Each box and whisker plot shows the position of the minimum, lower quartile, median, upper quartile, and maximum of the data, at baseline and at different times of treatment.
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