P. Burgel, I. Durieu, R. Chiron
Feb 18, 2021
Citations
5
Influential Citations
110
Citations
Quality indicators
Journal
American journal of respiratory and critical care medicine
Abstract
RATIONALE Elexacaftor-tezacaftor-ivacaftor is a cystic fibrosis transmembrane conductance regulator modulator combination, developed for cystic fibrosis (CF) patients with at least one Phe508del mutation. OBJECTIVES To evaluate the effects of elexacaftor-tezacaftor-ivacaftor in CF patients with advanced respiratory disease. METHODS A prospective observational study, including all patients aged ≥12 years and with ppFEV1<40 who initiated elexacaftor-tezacaftor-ivacaftor from December 2019 to August 2020 in France was conducted. Clinical characteristics were collected at initiation and at one and three months. Safety and effectiveness were evaluated by September 2020. National-level transplantation and mortality figures for 2020 were obtained from the French CF and transplant centers and registries. MAIN RESULTS Elexacaftor-tezacaftor-ivacaftor was initiated in 245 patients with a median [IQR] ppFEV1=29 [24; 34]. Mean (95% confidence interval) absolute increase in ppFEV1 was +15.1 (+13.8,+16.4; P<0.0001) and in weight was +4.2 kg (+3.9, +4.6; P<0.0001). The number of patients requiring long-term oxygen, non-invasive ventilation and/or enteral tube feeding decreased by 50%, 30% and 50%, respectively (P<0.01). Although 16 patients were on the transplant waiting list and 37 were undergoing transplantation evaluation at treatment initiation, only two were transplanted and one died. By September 2020 only five patients were still on transplantation path. Compared with the previous two years, a two-fold decrease in the number of lung transplantations in CF patients was observed in 2020, while the number of death without transplantation remained stable. CONCLUSIONS In patients with advanced disease, elexacaftor-tezacaftor-ivacaftor is associated with rapid clinical improvement, often leading to the indication for lung transplantation being suspended.