Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 18;14(12):4335.
doi: 10.3390/jcm14124335.

Reported Adverse Events in Patients with CF Receiving Treatment with Elexacaftor/Tezacaftor/Ivacaftor: 5 Years Observational Study

Francesca Lucca  1 , Ilaria Meneghelli  1 , Gloria Tridello  1 , Francesca Buniotto  1 , Giulia Cucchetto  1 , Sonia Volpi  1 , Emily Pintani  1 , Valentino Bezzerri  1   2 , Marco Cipolli  1
Affiliations

Reported Adverse Events in Patients with CF Receiving Treatment with Elexacaftor/Tezacaftor/Ivacaftor: 5 Years Observational Study

Francesca Lucca et al. J Clin Med. .

Abstract

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) treatment is showing remarkable beneficial effects in people with Cystic Fibrosis (pwCF) harboring the F508del mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Although this therapy is generally well tolerated in pwCF, some adverse events (AEs) have been recently described both in controlled studies and in post-marketing observations. Methods: We followed 414 pwCF carrying F508del CFTR that initiated ETI treatment, recording AEs for a period of 5 years. Results: A total of 142 AEs were reported. The most frequent AEs in the whole cohort were liver marker elevation, skin rush, epigastric pain, headache, and depression. Considering pediatric subjects, psychiatric and gastrointestinal disorders were the most frequent AEs. Only one patient reported a severe AE, leading to treatment discontinuation. In case of AEs, different decisions on ETI treatment were made, including temporary interruption and temporary or permanent dosage modification. Conclusions: Throughout the long-term observational period, almost 21% of pwCF experienced at least one AE. Psychiatric disorders, in particular attention deficit, were the most prevalent issue in our pediatric cohort, whereas adult patients mainly reported depression, anxiety and sleep disorders. This study therefore strengthen the recommendation of screening for changes in mental health during ETI treatment. AEs led to the permanent reduction of ETI dosage in 32% of cases, raising the issue of safety in relation to dosage reduction, efficacy, and minimum ETI levels. Eventually, this study highlights the need for a longitudinal monitoring of ETI safety since a significant number of AEs occurred after one year of treatment.

Keywords: CFTR modulators; cystic fibrosis; drug safety; elexacaftor; ivacaftor; tezacaftor.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
(A) ETI treatment adjustments in response to AEs for each SOC in all patients. (B) ETI treatment adjustments in response to AEs for each SOC in pediatric patients. (C) ETI treatment adjustments in response to AEs for each SOC in adult patients.
Figure 1
Figure 1
(A) ETI treatment adjustments in response to AEs for each SOC in all patients. (B) ETI treatment adjustments in response to AEs for each SOC in pediatric patients. (C) ETI treatment adjustments in response to AEs for each SOC in adult patients.
See this image and copyright information in PMC

References

    1. Riordan J.R., Rommens J.M., Kerem B.-S., Alon N., Rozmahel R., Grzelczak Z., Zielenski J., Lok S., Plavsic N., Chou J.-L., et al. Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science. 1989;245:1066–1073. doi: 10.1126/science.2475911. - DOI - PubMed
    1. Ratjen F., Bell S.C., Rowe S.M., Goss C.H., Quittner A.L., Bush A. Cystic fibrosis. Nat. Rev. Dis. Primers. 2015;1:15010. doi: 10.1038/nrdp.2015.10. - DOI - PMC - PubMed
    1. Van Goor F., Straley K.S., Cao D., González J., Hadida S., Hazlewood A., Joubran J., Knapp T., Makings L.R., Miller M., et al. Rescue of DeltaF508-CFTR trafficking and gating in human cystic fibrosis airway primary cultures by small molecules. Am. J. Physiol.-Lung Cell. Mol. Physiol. 2006;290:L1117–L1130. doi: 10.1152/ajplung.00169.2005. - DOI - PubMed
    1. Taylor-Cousar J.L., Robinson P.D., Shteinberg M., Downey D.G. CFTR modulator therapy: Transforming the landscape of clinical care in cystic fibrosis. Lancet. 2023;402:1171–1184. doi: 10.1016/S0140-6736(23)01609-4. - DOI - PubMed
    1. Heijerman H.G.M., McKone E.F., Downey D.G., Van Braeckel E., Rowe S.M., Tullis E., Mall M.A., Welter J.J., Ramsey B.W., McKee C.M., et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regiment in people with cystic fibrosis homozygous for the F508del mutation: A double-blind, randomised, phase 3 trial. Lancet. 2019;394:1940–1948. doi: 10.1016/S0140-6736(19)32597-8. - DOI - PMC - PubMed

LinkOut - more resources