Effects of elexacaftor/tezacaftor/ivacaftor therapy in children with cystic fibrosis – a comprehensive assessment using lung clearance index, spirometry, and functional and structural lung MRI

Streibel, C; Willers, Corin; Pusterla, Orso; Bauman, Grzegorz; Stranzinger, Enno; Brabandt, B; Bieri, Oliver; Curdy, Marion; Bullo, Marina; Frauchiger, Bettina Sarah; Korten, Insa; Krüger, Linn; Casaulta, Carmen; Ratjen, Félix; Latzin, Philipp; Kieninger, Elisabeth

doi:10.1016/j.jcf.2022.12.012

Cited by 27 publications

(14 citation statements)

References 29 publications

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“…Although randomized controlled trials demonstrated that ELX/TEZ/IVA was safe and effective, there are limited post-approval clinical data, particularly in children over two years old (52)(53)(54)(55)(56). BMI and ppFEV 1 are useful markers of clinical response to CFTR modulator treatment in children (57).…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Profiling of the Intestinal Microbiome in Children with Cystic Fibrosis Treated with Elexacaftor-Tezacaftor-Ivacaftor

Reasoner,

Bernard,

Waalkes

et al. 2023

Preprint

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The intestinal microbiome influences growth and disease progression in children with cystic fibrosis (CF). Elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA), the newest pharmaceutical modulator for CF, restores function of the pathogenic mutated CFTR channel. We performed a single-center longitudinal analysis of the effect of ELX/TEZ/IVA on the intestinal microbiome, intestinal inflammation, and clinical parameters in children with CF. Following ELX/TEZ/IVA, children with CF had significant improvements in BMI, ppFEV1 and required fewer antibiotics for respiratory infections. Intestinal microbiome diversity increased following ELX/TEZ/IVA coupled with a decrease in the intestinal carriage of Staphylococcus aureus, the predominant respiratory pathogen in children with CF. There was a reduced abundance of microbiome-encoded antibiotic-resistance genes. Microbial pathways for aerobic respiration were reduced after ELX/TEZ/IVA. The abundance of microbial acid tolerance genes was reduced, indicating microbial adaptation to increased CFTR function. In all, this study represents the first comprehensive analysis of the intestinal microbiome in children with CF receiving ELX/TEZ/IVA.

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Section: Discussionmentioning

confidence: 99%

Longitudinal Profiling of the Intestinal Microbiome in Children with Cystic Fibrosis Treated with Elexacaftor-Tezacaftor-Ivacaftor

Reasoner,

Bernard,

Waalkes

et al. 2023

Preprint

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“…Overall, results from MRI demonstrated the reversibility of abnormalities in the paranasal sinus and lung structures by ETI therapy, which correlated with the improvements observed in spirometry [ 64 ]. Streibel and collaborators also assessed the effects of ETI therapy on functional and structural lung abnormalities by MRI in 24 children with CF with at least one F508del-CFTR allele [ 66 ]. Clinical data, lung function, and MRI were collected one year before the start of ETI, soon after its start, and one year after it.…”

Section: Clinical Outcomes Of Eti Therapy In Case Reports Observation...mentioning

confidence: 99%

“…Lung function and BMI improved, while the frequency of acute exacerbations decreased after the start of ETI therapy. A correlation between all lung function parameters and MRI outcomes was observed [ 66 ]. Another observational study was performed by Stapleton and collaborators to assess the effects of ETI therapy on sinonasal symptoms of 34 adults with CF (average age of 27 years, 67% homozygous for F508del-CFTR) [ 67 ].…”

Section: Clinical Outcomes Of Eti Therapy In Case Reports Observation...mentioning

confidence: 99%

Elexacaftor-Tezacaftor-Ivacaftor: A Life-Changing Triple Combination of CFTR Modulator Drugs for Cystic Fibrosis

et al. 2023

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Cystic fibrosis (CF) is a potentially fatal monogenic disease that causes a progressive multisystemic pathology. Over the last decade, the introduction of CF transmembrane conductance regulator (CFTR) modulator drugs into clinical practice has profoundly modified the lives of many people with CF (PwCF) by targeting the fundamental cause of the disease. These drugs consist of the potentiator ivacaftor (VX-770) and the correctors lumacaftor (VX-809), tezacaftor (VX-661), and elexacaftor (VX-445). In particular, the triple combination of CFTR modulators composed of elexacaftor, tezacaftor, and ivacaftor (ETI) represents a life-changing therapy for the majority of PwCF worldwide. A growing number of clinical studies have demonstrated the safety and efficacy of ETI therapy in both short- and long-term (up to two years of follow-up to date) and its ability to significantly reduce pulmonary and gastrointestinal manifestations, sweat chloride concentration, exocrine pancreatic dysfunction, and infertility/subfertility, among other disease signs and symptoms. Nevertheless, ETI therapy-related adverse effects have also been reported, and close monitoring by a multidisciplinary healthcare team remains vital. This review aims to address and discuss the major therapeutic benefits and adverse effects reported by the clinical use of ETI therapy for PwCF.

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“…Air trapping, airway mucus plugging and bronchial wall thickening were reduced ( Bec et al, 2022 ; Graeber et al, 2022b ; FitzMaurice et al, 2022 ; Goralski et al, 2022 ; Fainardi et al, 2023 ). Likewise, functional MRI showed improvements in ventilation and perfusion ( Streibel et al, 2023 ). During sleep the episodes of oxygen desaturation, apnea and hypopnea decreased in adult pwCF ( Welsner et al, 2022 ; Giallongo et al, 2023 ).…”

Section: Pulmonarymentioning

confidence: 99%

Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor—Ivacaftor

Tümmler

2023

Front. Pharmacol.

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Triple combination therapy with the CFTR modulators elexacaftor (ELX), tezacaftor (TEZ) and ivacaftor (IVA) has been qualified as a game changer in cystic fibrosis (CF). We provide an overview of the body of literature on ELX/TEZ/IVA published between November 2019 and February 2023 after approval by the regulators. Recombinant ELX/TEZ/IVA-bound Phe508del CFTR exhibits a wild type conformation in vitro, but in patient’s tissue a CFTR glyoisoform is synthesized that is distinct from the wild type and Phe508del isoforms. ELX/TEZ/IVA therapy improved the quality of life of people with CF in the real-life setting irrespective of their anthropometry and lung function at baseline. ELX/TEZ/IVA improved sinonasal and abdominal disease, lung function and morphology, airway microbiology and the basic defect of impaired epithelial chloride and bicarbonate transport. Pregnancy rates were increasing in women with CF. Side effects of mental status changes deserve particular attention in the future.

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Effects of elexacaftor/tezacaftor/ivacaftor therapy in children with cystic fibrosis – a comprehensive assessment using lung clearance index, spirometry, and functional and structural lung MRI

Cited by 27 publications

References 29 publications

Longitudinal Profiling of the Intestinal Microbiome in Children with Cystic Fibrosis Treated with Elexacaftor-Tezacaftor-Ivacaftor

Longitudinal Profiling of the Intestinal Microbiome in Children with Cystic Fibrosis Treated with Elexacaftor-Tezacaftor-Ivacaftor

Elexacaftor-Tezacaftor-Ivacaftor: A Life-Changing Triple Combination of CFTR Modulator Drugs for Cystic Fibrosis

Post-approval studies with the CFTR modulators Elexacaftor-Tezacaftor—Ivacaftor

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