Elexacaftor-tezacaftor-ivacaftor Research Articles

P039 Effect of elexacaftor/tezacaftor/ivacaftor (ETI) on sweat chloride levels in children with cystic fibrosis (CF) – a real-world experience

Objectives: In clinical trials elexacaftor/tezacaftor/ivacaftor (ETI) has shown significant improvement in clinically important parameters in children with CF (cwCF) including reduction in sweat chloride levels. In our study we aimed to check effect of ETI on sweat chloride levels in cwCF in real-world clinical practice.

P079 Personalized CFTR modulator therapy for G85E and N1303K homozygous patients with cystic fibrosis

Objectives: The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators elexacaftor/tezacaftor/ivacaftor (ETI) are approved for people with CF (pwCF) and at least one F508del-allele in Europe. In the US, ETI label was expanded by >100 rare CFTR mutations responsive in fisher rat thyroid cells, including G85E, but not N1303K. However, the effect of ETI on G85E or N1303K CFTR proteins is unknown.

EPS5.05 Elexacaftor/tezacaftor/ivacaftor (ETI) - nutritional benefits are greatest for those in greatest need

Introduction: Phase 3 trials with elexacaftor/tezacaftor/ivacaftor (ETI) have reported on increases in weight alongside substantial pulmonary benefits. We aimed to assess the impact on nutritional outcomes 12 months following the introduction of ETI in clinical practice.

WS02.04 Triple HEMT in Pregnancy and Lactation: effects on the developing lung, gut and pancreas

Introduction/aim: The development of new cystic fibrosis (CF) drugs, including the highly effective modulator therapies (HEMT) such as elexacaftor-tezacaftor-ivacaftor (ETI), has enabled more women with CF to reach child-bearing age. However, safety of ongoing use of ETI during pregnancy and breastfeeding, especially for the baby’s developing organs, is unknown. We aim to investigate placental and milk transfer of maternally administered ETI in pre- and postnatal wildtype and F508del-CFTR rats and their bioaccumulation into the developing lungs, gut and pancreas.

P084 Willingness of people treated with elexacaftor/tezacaftor/ivacaftor (ETI) to participate in randomized clinical trials of new modulators and inhaled antibiotics

Objectives: Future CF drug development will require clinical trial participation by people with CF (pwCF) benefitting from the CFTR modulator elexacaftor/tezacaftor/ivacaftor (ETI).

WS10.01 The French Compassionate Programme of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with advanced lung disease and no F508del CFTR variant

Objective: The European Medicines Agency has approved the cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination elexacaftor-tezacaftor-ivacaftor (ETI) for people with cystic fibrosis (pwCF) carrying at least one F508del variant. The United States Food and Drug Administration (FDA) also approved ETI for pwCF carrying one of 177 rare variants. Our objective was to evaluate ETI in pwCF with advance lung disease and no F508del variant.

P319 Effects of elexacaftor/tezacaftor/ivacaftor (ETI) on nutrition parameters and resting energy expenditure (REE) in people with cystic fibrosis (pwCF)

Cystic fibrosis (CF) is associated with increased energy requirement, energy loss and inadequate energy intake. With the approval of ETI, a highly effective CFTR-modulator therapy became available for 90% of pwCF. First studies have shown promising improvements in anthropometric parameters. We investigated the short-term change of the nutritional status under ETI and potential mechanisms of bodyweight (bw) gain.

P164 Elexacaftor/tezacaftor/ivacaftor (ETI)– home spirometry during the first 14 days of treatment

In Belgium, ETI reimbursement for eligible patients with cystic fibrosis was very late (September 2022). Under ETI treatment, substantial improvement is well documented after 2 weeks. Yet, little is known about what more precisely happens during these 14 days. We aimed to monitor this period closely.

P349 Body image perceptions and elexacaftor/tezacaftor/ivacaftor (ETI) use in adolescents living with cystic fibrosis in the United States

Adolescents with CF (AwCF) experience stress associated with eating, weight, and body image due to high caloric needs and pressure to maintain weight. Societal ideals can create even greater risk. Elexacaftor/tezacaftor/ivacaftor (ETI) has dramatically improved outcomes in CF, including contributing to weight gain. No research has examined body image and adherence to ETI in AwCF. This study examines perspectives of US AwCF on how body image may relate to ETI adherence.

P156 Treatment with the CFTR modulator [HB1] elexacafor/tezacaftor/ivacaftor reduces immunological response to airway Aspergillus in people with cystic fibrosis

Amongst people with Cystic Fibrosis, Aspergillus fumigatus is the most frequently cultured fungal pathogen in sputum samples. Elexacaftor/tezacaftor/ivacaftor (ETI) is a CFTR modulator which results in significant improvements in lung function. We investigated the effect of ETI therapy on the serological response to Aspergillus in adult CF patients prescribed ETI.

WS08.02 Change in hepatobiliary ultrasound measures, incl. shear wave elastography, after introduction of elexacaftor/tezacaftor/ivacaftor: results from 12-month follow-up in the Danish cystic fibrosis cohort

Objectives: A new era in cystic fibrosis (CF) since the introduction of CF transmembrane conductance regulator modulators with elexacaftor/tezacaftor/ivacaftor (ETI) is marked by significantly improved lung function and nutritional status. However, the impact of ETI on the liver remains poorly characterized, as advanced liver disease was an exclusion criterion in clinical trials. Clinical experience from the Danish CF cohort has shown ETI to be generally well-tolerated in term of liver biomarkers. The objective of this study is to assess hepatobiliary ultrasonographic changes before and twelve months after the initiation of ETI.

EPS5.01 Change in gut microbiota following elexacaftor/tezacaftor/ivacaftor (ETI) therapy: preliminary analysis

Objectives: Abnormal cystic fibrosis transmembrane conductance regulator (CFTR) function is associated with gut dysbiosis in people with cystic fibrosis. The recently introduced elexacaftor/tezacaftor/ivacaftor (ETI) therapy has proved highly effective at improving clinical status, reducing pulmonary exacerbations and increasing weight. There is presently little data on the impact of ETI on CF-related gut dysbiosis. In this study, we explored compositional changes of the gut microbiota following ETI therapy.

P247 ETI reduces antibiotic treatment days in people with cystic fibrosis – a real-life observation

Since its approval, Elexacaftor/Tezacaftor/Ivacaftor (ETI) has improved lung function and decreased the number of pulmonary exacerbations in people with cystic fibrosis (pwCF). Here, we investigated the influence of ETI on the amount of oral and intravenous (iv) antibiotic therapies in pwCF since the initiation of ETI therapy.

EPS1.07 Impact of elexacaftor/tezacaftor/ivacaftor (ETI) therapy on Aspergillus fumigatus serology in adults with cystic fibrosis

Objectives: Aspergillus fumigatus is the commonest fungi to colonise the airways of people with cystic fibrosis (CF). Colonisation, both with or without the presence of allergic bronchopulmonary aspergillosis (AGPA), has been found to be associated with increased respiratory exacerbations, hospitalisations, reduced pulmonary function and CT scan abnormalities. Management with anti-fungal agents has shown limited clinical benefit, as well as issues with side effects and drug resistance. The effect of CFTR modulator therapies; revolutionary in the management of CF in recent years, on Aspergillus related disease in CF has yet to be established. We aimed to assess whether elexacaftor-tezacaftor-ivacaftor (ETI) therapy impacted on Asp. fumigatus serology in a population of adults with CF.

EPS5.08 Elexacaftor/tezacaftor/ ivacaftor reduces need for pancreatic enzymes, enteral feeding and omeprazole use without causing excessive weight gain: a 2-year observational study

Introduction: Short term studies of Elexacaftor/tezacaftor/ivacaftor (ETI) have shown increasing weight gain and modest improvements in GI symptoms. Since August 2020, all CF patients aged >12 years attending our Paediatric Service have been treated with ETI according to UK licencing. In this real-world study, we assessed changes in nutritional status after starting ETI, effects on the need for enteral feeding, use of pancreatic enzymes (PERT), endocrine function and medication.

WS01.04 Longtime follow-up on exercise capacity and quality of life in people with cystic fibrosis receiving elexacaftor/tezacaftor/iIvacaftor – a Copenhagen cohort

Background: People with Cystic Fibrosis (CF) have decreased exercise capacity and quality of life (HRQoL) compared to the background population. Since 2020 third generation CF transmembrane conductance regulator modulator, elexacaftor, tezacaftor, ivacaftor (ETI) was approved for people with CF from the age of 12 in Denmark. The results of the treatment over short time, show among other increased lungfunction, HRQoL and BMI. The longterm effect regarding the new treatment is to date not fully evaluated especially not regarding exercise capacity.

EPS6.02 Elexacaftor/tezacaftor/ivacaftor results in substantial improvements in chest CT scores in people with cystic fibrosis aged 12 and above over one year of treatment

Background: Elexacaftor-Tezacaftor-Ivacaftor (ETI) is associated with improvements in pulmonary function, sweat chloride and nutrition in people with CF (PwCF) and the F508del mutation. As part of RECOVER, a multi-centre post-approval study examining the impact of ETI in PwCF, we sought to establish the impact of one year of ETI on structural lung disease scores by chest CT.

P052 Efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with normal/near normal FEV1 (≥70%)

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) demonstrated high efficacy in clinical trials that included people with CF (pwCF) with FEV1 between 40–90% and later with less than 40%. It is unclear if pwCF with mild lung disease can have measurable effect of ETI.

P020 Therapy with elexacaftor/tezacaftor/ivacaftor in a patient with compound heterozygous CFTR mutation and the complex CFTR-allele Phe508del; Leu467Phe

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy with elexacaftor/tezacaftor/ivacaftor (ETI) was shown to be highly efficacious in patients who have at least one copy of the F508del variant. Cis variants in F508del mutations might influence the response to CFTR modulator therapy. We report the response to ETI in a patient with CF who is heterozygous for the complex Phe508del;Leu467Phe allele.

EPS6.08 Cystic fibrosis elexacaftor/tezacaftor/ivacaftor in liver or kidney transplanted people with cystic fibrosis using Tacrolimus, a drug-drug interaction study

Background: Although elexacaftor/tezacaftor/ivacaftor (ETI) has a proven robust effect in people with cystic fibrosis (pwCF) with at least one F508 del mutation, its use is not recommended for pwCF after solid organ transplantation because of expected drug-drug interactions with antirejection therapy, mostly tacrolimus. With our drug-drug interaction study we aim to improve insight into the safety and clinical benefits of co-administration of ETI and tacrolimus in liver or kidney transplanted adult pwCF.