Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials.

Background: The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor-tezacaftor-deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor-tezacaftor-deutivacaftor compared with standard of care elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older.

Longitudinal changes in BMD in adults with cystic fibrosis.

Improved survival in people with cystic fibrosis (pwCF) presents new complexities of care, including CF-related bone disease, a common complication in older pwCF. The trajectory of bone loss with age in this population remains unclear. The objective of this study was to estimate the average rate of change in BMD in adults with CF.

Clinical outcomes after liver transplant in people with cystic fibrosis: A systematic review and meta-analysis.

Background: Data on the impact of liver transplantation (LT) in cystic fibrosis (CF) on lung function and exacerbations are limited. The objective of this study was to summarize the literature on lung function, nutritional status, survival, and complications following LT in people with CF.

Methods: Three databases were searched until September 2023, to identify the impact of LT in CF.

Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and at least one allele: 144-week interim results from a 192-week open-label extension study.

Background: In two pivotal phase 3 trials, up to 24 weeks of treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was efficacious and safe in patients with cystic fibrosis (CF) ≥12 years of age who have at least one allele. The aim of this study is to assess long-term safety and efficacy of ELX/TEZ/IVA in these patients.

Methods: In this phase 3, open-label, single-arm extension study, participants with -minimal function (from a 24-week parent study; n=399) or - (from a 4-week parent study; n=107) genotypes receive ELX/TEZ/IVA at the same dose (ELX 200 mg once daily, TEZ 100 mg once daily and IVA 150 mg every 12 h).

Elexacaftor/Tezacaftor/Ivacaftor Treatment and Depression-related Events.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and efficacious in people with cystic fibrosis (pwCF) aged 2 years and older with at least one allele or more. After U.S.

Phase 3 Open-Label Clinical Trial of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged 2-5 Years with Cystic Fibrosis and at Least One Allele.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and effective in people with cystic fibrosis (CF) aged ⩾6 years with at least one allele but has not been studied in younger children. To evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of ELX/TEZ/IVA in children with CF aged 2-5 years. In this phase 3, open-label, two-part study (parts A and B), children weighing <14 kg (on Day 1) received ELX 80 mg once daily (qd), TEZ 40 mg qd, and IVA 60 mg each morning and 59.

Safety and efficacy of vanzacaftor-tezacaftor-deutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials.

Background: Elexacaftor-tezacaftor-ivacaftor has been shown to be safe and efficacious in people with cystic fibrosis and at least one F508del allele. Our aim was to identify a novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination capable of further increasing CFTR-mediated chloride transport, with the potential for once-daily dosing.

Methods: We conducted two phase 2 clinical trials to assess the safety and efficacy of a once-daily combination of vanzacaftor-tezacaftor-deutivacaftor in participants with cystic fibrosis who were aged 18 years or older.

Management of pregnancy in cystic fibrosis.

Unlabelled: With recent therapeutic advances in care, people with cystic fibrosis (CF) are living longer and healthier lives. Development of the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies has led to improved function of the CFTR protein resulting in improved lung function, decreased rates of pulmonary exacerbations and improved nutritional status for the majority of people with CF. Given improved quality and quantity of life, more people with CF are considering becoming pregnant than ever before.

Genomic epidemiology of Mycobacterium abscessus in a Canadian cystic fibrosis centre.

The Mycobacterium abscessus complex causes significant morbidity and mortality among patients with Cystic Fibrosis (CF). It has been hypothesized that these organisms are transmitted from patient to patient based on genomics. However, few studies incorporate epidemiologic data to confirm this hypothesis.

Frailty predicts outcomes in cystic fibrosis patients listed for lung transplantation.

Background: Survival predictors are not established for cystic fibrosis (CF) patients listed for lung transplantation (LT). Using the deficit accumulation approach, we developed a CF-specific frailty index (FI) to allow risk stratification for adverse waitlist and post-LT outcomes.

Methods: We studied adult CF patients listed for LT in the Toronto LT Program (development cohort 2005-2015) and the Swiss LT centres (validation cohort 2008-2017).

The negative impact of chronic rhinosinusitis on the health-related quality of life among adult patients with cystic fibrosis.

Background: With improved survival in cystic fibrosis (CF) patients, it is crucial to evaluate the impact of chronic co-morbidities such as chronic rhinosinusitis (CRS). The objectives were 1) To determine the prevalence of CRS with a large series of CF patients 2) To evaluate the impact of CRS on the Health-Related Quality of Life (HRQoL) of CF patients and 3) To compare CRS-specific, CF-specific and general HRQoL instruments.

Methods: Consecutive CF patients from the Toronto Adult Cystic Fibrosis Centre were recruited between March 2018 and January 2020.

Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: a 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial.

Background: Elexacaftor plus tezacaftor plus ivacaftor is a triple-combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be generally safe and efficacious in people with cystic fibrosis aged 12 years or older with at least one F508del-CFTR allele. We aimed to assess the magnitude and durability of the clinical effects of this triple combination regimen in people with cystic fibrosis homozygous for the F508del-CFTR mutation.

Methods: We conducted a multicentre, randomised, double-blind, active-controlled, phase 3b trial of elexacaftor plus tezacaftor plus ivacaftor at 35 medical centres in Australia, Belgium, Germany, and the UK.

Fourier Transform Infrared Spectroscopy for Typing Burkholderia cenocepacia ET12 Isolates.

The IR Biotyper and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) using ClinProTools software (MALDI-TOF MS-ClinProTools) are two novel typing methods that rely on the analysis of carbohydrate and peptide residues in intact bacterial cells. These two methods have shown promising results in the rapid and accurate typing of bacteria. In this study, we evaluated these novel typing methods in comparison with genotypic typing for cluster analysis of Burkholderia cenocepacia epidemic strain ET12, isolated from adult cystic fibrosis patients.

Triple Therapy for Cystic Fibrosis -Gating and -Residual Function Genotypes.

Background: Elexacaftor-tezacaftor-ivacaftor is a small-molecule cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be efficacious in patients with at least one allele, which indicates that this combination can modulate a single allele. In patients whose other allele contains a gating or residual function mutation that is already effectively treated with previous CFTR modulators (ivacaftor or tezacaftor-ivacaftor), the potential for additional benefit from restoring Phe508del CFTR protein function is unclear.

Methods: We conducted a phase 3, double-blind, randomized, active-controlled trial involving patients 12 years of age or older with cystic fibrosis and -gating or -residual function genotypes.

Riociguat for the treatment of Phe508del homozygous adults with cystic fibrosis.

Background: Riociguat is a first-in-class soluble guanylate cyclase stimulator for which preclinical data suggested improvements in cystic fibrosis transmembrane conductance regulator (CFTR) function.

Methods: This international, multicenter, two-part, Phase II study of riociguat enrolled adults with cystic fibrosis (CF) homozygous for Phe508del CFTR. Part 1 was a 28-day, randomized, double-blind, placebo-controlled study in participants not receiving CFTR modulator therapy.

A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One Allele.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be efficacious and safe in patients ≥12 years of age with cystic fibrosis and at least one (cystic fibrosis transmembrane conductance regulator) allele, but it has not been evaluated in children <12 years of age. To assess the safety, pharmacokinetics, and efficacy of ELX/TEZ/IVA in children 6 through 11 years of age with -minimal function or - genotypes. In this 24-week open-label phase 3 study, children ( = 66) weighing <30 kg received 50% of the ELX/TEZ/IVA adult daily dose (ELX 100 mg once daily, TEZ 50 mg once daily, and IVA 75 mg every 12 h) whereas children weighing ⩾30 kg received the full adult daily dose (ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 h).