Use of Elexacaftor/tezacaftor/ivacaftor Combination in Pregnancy

Overview

Journal Arch Gynecol Obstet

Specialty Gynecology & Obstetrics

Date 2023 Mar 13

PMID 36907900

Authors

Giuseppe Cimino

Sara Sorrenti

Manuel Murciano

Paola Galoppi

Fiorentina Ascenzioni

Bruno Botta

Roberto Brunelli

Affiliations

Soon will be listed here.

Abstract

Introduction: Management of cystic fibrosis has recently stepped forward with the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, although data on potential adverse effects are lacking for many categories of patients, such as pregnant women.

Methods: We report one of the first reports on the outcome of pregnancy in a woman treated with Elexacaftor/Tezacaftor/Ivacaftor during the second and third trimester of pregnancy, showing a significant improvement of respiratory status, compared with the first trimester when the medication was discontinued due to unknown and, therefore, potential teratogenic effects. Also, we performed the review of the existing literature on the topic.

Results: The course of pregnancy was uneventful, with reference to major obstetric complications, and the patient delivered a healthy neonate. These results were similar to those coming from other short series of pregnant women affected by cystic fibrosis and treated with CFTR modulators during pregnancy.

Conclusions: Thus, despite the lack of evidence on the topic, the use of Elexacaftor/Tezacaftor/Ivacaftor in pregnancy seems to be apparently not associated with major adverse events, thus opening optimistic scenarios in terms of management of these patients.

Citing Articles

Pregnancy in People With Cystic Fibrosis Treated With Highly Effective Modulator Therapy.

Goralski J, Talati A, Hardisty E, Vora N Obstet Gynecol. 2024; 145(1):47-54.

PMID: 39666984 PMC: 11630662. DOI: 10.1097/AOG.0000000000005732.

CFTR dysfunction leads to defective bacterial eradication on cystic fibrosis airways.

Wu M, Chen J Front Physiol. 2024; 15:1385661.

PMID: 38699141 PMC: 11063615. DOI: 10.3389/fphys.2024.1385661.

In utero and postnatal ivacaftor/lumacaftor therapy rescues multiorgan disease in CFTR-F508del ferrets.

Evans I, Sun X, Liang B, Vegter A, Guo L, Lynch T JCI Insight. 2024; 9(8.

PMID: 38646935 PMC: 11141870. DOI: 10.1172/jci.insight.157229.

References

Shteinberg M, Haq I, Polineni D, Davies J . Cystic fibrosis. Lancet. 2021; 397(10290):2195-2211. DOI: 10.1016/S0140-6736(20)32542-3. View

Riordan J, Rommens J, Kerem B, Alon N, Rozmahel R, Grzelczak Z . Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989; 245(4922):1066-73. DOI: 10.1126/science.2475911. View

Sueblinvong V, Whittaker L . Fertility and pregnancy: common concerns of the aging cystic fibrosis population. Clin Chest Med. 2007; 28(2):433-43. DOI: 10.1016/j.ccm.2007.02.009. View

Gilljam M, Antoniou M, Shin J, Dupuis A, Corey M, Tullis D . Pregnancy in cystic fibrosis. Fetal and maternal outcome. Chest. 2000; 118(1):85-91. DOI: 10.1378/chest.118.1.85. View

Barak A, Dulitzki M, Efrati O, Augarten A, Szeinberg A, Reichert N . Pregnancies and outcome in women with cystic fibrosis. Isr Med Assoc J. 2005; 7(2):95-8. View

Tan E, Tan E . Alterations in physiology and anatomy during pregnancy. Best Pract Res Clin Obstet Gynaecol. 2013; 27(6):791-802. DOI: 10.1016/j.bpobgyn.2013.08.001. View

Davis P . Therapy for cystic fibrosis--the end of the beginning?. N Engl J Med. 2011; 365(18):1734-5. DOI: 10.1056/NEJMe1110323. View

Hoy S . Elexacaftor/Ivacaftor/Tezacaftor: First Approval. Drugs. 2019; 79(18):2001-2007. DOI: 10.1007/s40265-019-01233-7. View

Zaher A, Elsaygh J, Elsori D, Elsaygh H, Sanni A . A Review of Trikafta: Triple Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulator Therapy. Cureus. 2021; 13(7):e16144. PMC: 8266292. DOI: 10.7759/cureus.16144. View

10.

Veit G, Roldan A, Hancock M, Da Fonte D, Xu H, Hussein M . Allosteric folding correction of F508del and rare CFTR mutants by elexacaftor-tezacaftor-ivacaftor (Trikafta) combination. JCI Insight. 2020; 5(18). PMC: 7526550. DOI: 10.1172/jci.insight.139983. View

11.

Krasnowska E, Pittaluga E, Brunati A, Brunelli R, Costa G, De Spirito M . N-acetyl-l-cysteine fosters inactivation and transfer to endolysosomes of c-Src. Free Radic Biol Med. 2008; 45(11):1566-72. DOI: 10.1016/j.freeradbiomed.2008.09.012. View

12.

Middleton P, Mall M, Drevinek P, Lands L, McKone E, Polineni D . Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019; 381(19):1809-1819. PMC: 7282384. DOI: 10.1056/NEJMoa1908639. View

13.

Heijerman H, McKone E, Downey D, Van Braeckel E, Rowe S, Tullis E . Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019; 394(10212):1940-1948. PMC: 7571408. DOI: 10.1016/S0140-6736(19)32597-8. View

14.

Trimble A, Donaldson S . Ivacaftor withdrawal syndrome in cystic fibrosis patients with the G551D mutation. J Cyst Fibros. 2017; 17(2):e13-e16. DOI: 10.1016/j.jcf.2017.09.006. View

15.

Taylor-Cousar J . CFTR Modulators: Impact on Fertility, Pregnancy, and Lactation in Women with Cystic Fibrosis. J Clin Med. 2020; 9(9). PMC: 7563981. DOI: 10.3390/jcm9092706. View

16.

Vekaria S, Popowicz N, White S, Mulrennan S . To be or not to be on CFTR modulators during pregnancy: Risks to be considered. J Cyst Fibros. 2019; 19(2):e7-e8. DOI: 10.1016/j.jcf.2019.12.004. View

17.

Trimble A, McKinzie C, Terrell M, Stringer E, Esther Jr C . Measured fetal and neonatal exposure to Lumacaftor and Ivacaftor during pregnancy and while breastfeeding. J Cyst Fibros. 2018; 17(6):779-782. PMC: 6354249. DOI: 10.1016/j.jcf.2018.05.009. View

18.

Riccio M, Carnevale G, Cardinale V, Gibellini L, De Biasi S, Pisciotta A . The Fas/Fas ligand apoptosis pathway underlies immunomodulatory properties of human biliary tree stem/progenitor cells. J Hepatol. 2014; 61(5):1097-105. DOI: 10.1016/j.jhep.2014.06.016. View

19.

Ladores S, Kazmerski T, Rowe S . A Case Report of Pregnancy During Use of Targeted Therapeutics for Cystic Fibrosis. J Obstet Gynecol Neonatal Nurs. 2016; 46(1):72-77. DOI: 10.1016/j.jogn.2016.08.011. View

20.

Kaminski R, Nazareth D . A successful uncomplicated CF pregnancy while remaining on Ivacaftor. J Cyst Fibros. 2015; 15(1):133-4. DOI: 10.1016/j.jcf.2015.11.013. View