In patients with cystic fibrosis (CF) with advanced lung disease, initiation of elexacaftor-tezacaftor-ivacaftor is associated with rapid clinical improvement and a decreased need for lung transplantation, according to study results published in the American Journal of Respiratory and Critical Care Medicine.

Elexacaftor-tezacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination developed for patients with CF and at least one Phe508del mutation. Patients with advanced lung disease have not been eligible to participate in elexacaftor-tezacaftor-ivacaftor clinical trials because of a high risk of severe adverse events with lumacaftor-ivacaftor and a low likelihood of significant improvement in lung function. Therefore, when it comes to patients with advanced lung disease treated with CFTR modulators, data are limited. To the researchers’ knowledge, no clinical study has been conducted to evaluate the effectiveness of elexacaftor-tezacaftor-ivacaftor in patients with CF with advanced lung disease.

Researchers in France conducted a prospective observational study in 245 patients aged 12 years and older and with a forced expiratory volume in 1 second (FEV1) percent predicted of less than 40% (median FEV1 percent predicted, 29) who initiated elexacaftor-tezacaftor-ivacaftor from December 2019 to August 2020. Clinical characteristics were collected at initiation and at 1 and 3 months, and safety and effectiveness were evaluated by September 2020. The researchers found a mean absolute increase in FEV1 percent predicted of +15.1 (P <.0001) and in weight of +4.2 kg (P <.0001).


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The number of patients requiring long-term oxygen, noninvasive ventilation, and/or enteral tube feeding decreased by 50%, 30%, and 50%, respectively (P <.001). Although 16 patients were on the transplant waiting list and 37 were undergoing lung transplantation evaluation at treatment initiation, only 2 received transplants. Another patient, for whom transplantation was not indicated because of an active infection, died. By September 2020, only 5 patients remained on the transplantation path. Compared with the previous 2 years, there was a 2-fold decrease in the number of lung transplantations in patients with CF in 2020 while the number of deaths without transplantation remained stable.

The study authors concluded, “Although these early effects should be confirmed over a longer period of time and in other countries, these data suggest that elexacaftor-tezacaftor-ivacaftor can have a major impact on the life expectancy of people with CF.”

Reference

Burgel P-R, Durieu I, Chiron R, et al; for the French Cystic Fibrosis Reference Network study group. Rapid improvement after starting elexacaftor-tezacaftor-ivacaftor in patients with cystic fibrosis and advanced pulmonary disease.  Am J Respir Crit Care Med. Published online February 18, 2021. doi:10.1164/rccm.202011-4153OC