Case Series on the Combined Therapy with Elexacaftor/Tezacaftor/Ivacaftor During Pregnancy in Women with Severe Cystic Fibrosis: A Retrospective Report from an Italian Centre

Abstract

In patients with cystic fibrosis (CF), infertility is a common issue in men, while women often experience subfertility. The introduction of CF transmembrane conductance regulator (CFTR) modulators has improved disease progression and enhanced quality of life, consequently leading to an increase in unplanned pregnancies. This article describes six cases of pregnancies in five patients diagnosed with severe CF who were treated with the combined therapy of elexacaftor/tezacaftor/ivacaftor (ETI). All women were under regular clinical and instrumental monitoring at the Regional CF Center for Adults at the University of Naples Federico II. The reported pregnancies were spontaneous, and all patients were followed throughout their pregnancies. Two pregnancies were carried to term by the same patient. All five patients with a severe CF phenotype were able to experience pregnancy without stopping their ETI treatment without any complications. In two cases, the patients chose to continue ETI therapy while breastfeeding, and there were no adverse events reported. A cesarean delivery was preferred in all cases to prevent potential respiratory distress. These five patients represent some of the few cases in Italy where pregnancy was achieved without interrupting treatment with ETI. However, the lack of more reliable data necessitates that doctors and patients carefully evaluate the risks and benefits of continuing or discontinuing treatment with CFTR modulators. In conclusion, the increasing number of pregnancies and the desire for children expressed by women with CF highlight the need for more data on the long-term effects of CFTR modulators.

Keywords: CFTR modulator safety; cystic fibrosis; pregnancy.