Search

Background: Elexacaftor-tezacaftor-ivacaftor induces rapid clinical improvement in patients with cystic fibrosis (CF) and advanced pulmonary disease, often leading to suspend the indication for lung transplantation. Yet no long-term data is available in lung transplant candidates., Methods: Lung transplant candidates (defined as being waitlisted for lung transplantation or considered for listing within 3 months) who have initiated elexacaftor-tezacaftor-ivacaftor were identified in the French cohort of patients with CF and advanced pulmonary disease. Patients were prospectively followed to evaluate treatment safety and effectiveness from initiation to July 20th, 2021., Results: Among the 331 patients with advanced CF pulmonary disease who initiated elexacaftor-tezacaftor-ivacaftor, 65 were lung transplant candidates (17 listed for transplantation, 48 considered for listing within 3 months). Median [IQR] follow-up time was 363 [329; 377] days. At the end of the follow-up period, two patients were transplanted five and 11 days following treatment initiation, two were listed for transplantation, and 61 no longer met transplantation criteria. Improvement in percent predicted forced expiratory volume in 1 s (ppFEV 1 ) at one month was +13.4% (95% confidence interval, 10.3%-16.5%; P < 0.0001) and remained stable thereafter. Treatment burden decreased substantially, with an 86% decrease in the need for intravenous antibiotics, 59% for oxygen therapy and 62% for non-invasive ventilation., Conclusion: In lung transplant candidates eligible for elexacaftor-tezacaftor-ivacaftor, the rapid improvement following initiation of treatment persisted over one year with a reduction in treatment burden and lung transplantation could be safely deferred in most patients., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest related to the work submitted for publication., (Copyright © 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Lung clearance index (LCI) is a biomarker of ventilation inhomogeneity. Data are scarce on its usefulness in daily practice for monitoring the effects of treatments in older children and adults with CF. In this French observational study of lumacaftor-ivacaftor, 63 of 845 patients (7.5%) had available LCI performed at baseline and at six (M6; n=34) or 12 months (M12; n=46) after lumacaftor-ivacaftor initiation. At inclusion, median [IQR] age was 16 years [13-17], ppFEV 1 was 72.8 [59.6-80.7], and LCI was 12.3 [10.3-15.0]. At both M6 and M12, no statistically significant LCI increases of 0.13 units or 1.34% (95% CI: -4.85-7.53) and 0.6 units or 6.66% (95% CI: -0.03-13.5) were observed. Discordant results between LCI and ppFEV 1 were observed in one-third of the patients. In daily practice, LCI monitoring in adolescents and young adults with moderate lung disease gives results that are more heterogenous than those reported in children with milder disease., (Copyright © 2021 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Phase 3 trials have demonstrated the safety and efficacy of lumacaftor-ivacaftor (LUMA-IVA) in patients with cystic fibrosis (CF) homozygous for the Phe508del CFTR mutation and percent predicted forced expiratory volume in 1 s (ppFEV 1 ) between 40 and 90. Marketing authorizations have been granted for patients at all levels of ppFEV 1 ., Methods: To evaluate the safety and effectiveness of LUMA-IVA over the first year of treatment in patients with ppFEV 1 <40 or ppFEV 1 ≥90 in comparison with those with ppFEV 1 [40-90[. Analysis of data collected during a real world study, which included all patients aged ≥12 years who started LUMA-IVA in 2016 across all 47 French CF centers., Results: 827 patients were classified into 3 subgroups according to ppFEV 1 at treatment initiation (ppFEV 1 <40, n = 121; ppFEV 1 [40-90[, n = 609; ppFEV 1 ≥90, n = 97). Treatment discontinuation rate was higher in ppFEV 1 <40 patients (28.9%) than in those with ppFEV 1 [40-90[(16.4%) or ppFEV 1 ≥90 (17.5%). In patients with uninterrupted treatment, significant increase in ppFEV 1 occurred in the ppFEV 1 [40-90[subgroup (+2.9%, P<0.001), and in those ppFEV 1 <40 (+0.5%, P = 0.03) but not in those with ppFEV 1 ≥90 (P = 0.46). Compared with the year prior to initiation, the number of days of intravenous antibiotics were reduced in all subgroups, although 72% of patients with ppFEV 1 <40 still experienced at least one exacerbation/year under LUMA-IVA. Comparable increase in body mass index was seen in the three subgroups., Conclusion: Phe508del homozygous CF patients benefit from LUMA-IVA at all levels of baseline lung function , but the characteristics and magnitude of the response vary depending on ppFEV 1 at baseline., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest related to the work submitted for publication., (Copyright © 2020. Published by Elsevier B.V.)