Multisystemic Effects of Elexacaftor–Tezacaftor–Ivacaftor in Adults with Cystic Fibrosis and Advanced Lung Disease
Pierre‐Régis Burgel, Jean-Louis Paillasseur, I. Durieu, Martine Reynaud‐Gaubert, Rébecca Hamidfar, M. Murris‐Espin, Isabelle Danner‐Boucher, R. Chiron, Sylvie Leroy, Benoît Douvry, Dominique Grenet, Laurent Mély, Sophie Ramel, Sylvie Montcouquiol, Espérie Burnet, El Hassane Ouaalaya, Philippe Sogni, Jennifer Da Silva, Clémence Martin
Abstract
Abstract Rationale Limited data exist on the safety and effectiveness of elexacaftor-tezacaftor-ivacaftor (ETI) in people with cystic fibrosis (pwCF) and advanced lung disease. Objectives To evaluate the effects of ETI in an unselected population of pwCF and advanced lung disease. Methods A prospective observational study, including all adults aged 18 years and older with percentage predicted forced expiratory volume in 1 second (ppFEV1) ⩽ 40 who initiated ETI from December 2019 to June 2021 in France, was conducted. PwCF were followed until August 8, 2022. Results ETI was initiated in 434 pwCF with a median ppFEV1 of 30 (interquartile range, 25–35), including 27 with severe cystic fibrosis liver disease and 183 with diabetes. PwCF were followed for a median of 587 (interquartile range, 396–728) days after ETI initiation. Discontinuation of ETI occurred in 12 (2.8%) pwCF and was due mostly to lung transplantation (n = 5) or death (n = 4). Absolute increase in ppFEV1 by a mean of +14.2% (95% confidence interval, 13.1–15.4%) occurred at 1 month and persisted throughout the study. Increase in ppFEV1 in the youngest age quartile was almost twice that of the oldest quartile (P < 0.001); body mass index < 18.5 kg/m2 was found in 38.6% at initiation versus 11.3% at 12 months (P = 0.0001). Increases in serum concentrations of vitamins A and E, but not 25-hydroxy vitamin D3, were observed. Significant reductions in the percentages of pwCF using oxygen therapy, noninvasive ventilation, nutritional support, and inhaled and systemic therapies (including antibiotics) were observed; insulin was discontinued in 12% of patients with diabetes. Conclusions ETI is safe in pwCF and advanced lung disease, with multisystem pulmonary and extrapulmonary benefits.