Magnetic resonance imaging detects improvements of pulmonary and paranasal sinus abnormalities in response to elexacaftor/tezacaftor/ivacaftor therapy in adults with cystic fibrosis

Wucherpfennig, Lena; Triphan, Simon M. F.; Wege, Sabine; Kauczor, Hans‐Ulrich; Heußel, Claus Peter; Schmitt, Niclas; Wuennemann, Felix; Mayer, Victoria; Sommerburg, Olaf; Mall, Marcus; Eichinger, Monika; Wielpütz, Mark O.

doi:10.1016/j.jcf.2022.03.011

Cited by 44 publications

(33 citation statements)

References 26 publications

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“…While perhaps not surprising, this helps to validate that observed ventilation abnormalities are truly a function of structural airways disease and not likely reflecting transient bronchoconstriction or other imaging artifacts. Our findings are also consistent with recent publications [ 14 , 18 ] that showed lung structural improvements after treatment with elexacaftor/tezacaftor/ivacaftor are driven by changes in bronchiectasis/airway wall thickening and mucus plugging. Our study adds to the growing body of literature that structural improvements are detectable within 4 weeks of starting highly effective CFTR modulator therapy and correspond to improvements in ventilation defects detected by 19 F MRI.…”

Section: Discussionsupporting

confidence: 93%

Dynamic Perfluorinated Gas MRI Shows Improved Lung Ventilation in People with Cystic Fibrosis after Elexacaftor/Tezacaftor/Ivacaftor: An Observational Study

Goralski

Chung

Ceppe

et al. 2022

JCM

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The availability of highly effective CFTR modulators is revolutionizing the treatment of cystic fibrosis (CF) and drastically improving outcomes. MRI-based imaging modalities are now emerging as highly sensitive endpoints, particularly in the setting of mild lung disease. Adult CF patients were recruited from a single center prior to starting treatment with E/T/I. The following studies were obtained before and after one month on treatment: spirometry, multiple breath nitrogen washout (MBW), 1H UTE MRI (structural images) and 19F MRI (ventilation images). Changes between visits were calculated, as were correlations between FEV1, lung clearance index (LCI), MRI structural scores, and MRI-based ventilation descriptors. Eight subjects had complete datasets for evaluation. Consistent with prior clinical trials, FEV1 and LCI improved after 28 days of E/T/I use. 1H UTE MRI detected improvements in bronchiectasis/airway wall thickening score and mucus plugging score after 28 days of therapy. 19F MRI demonstrated improvements in fractional lung volume with slow gas washout time (FLV↑tau2) and ventilation defect percentage (VDP). Improvements in FLV↑tau2 and VDP correlated with improvement in FEV1 (r = 0.81 and 0.86, respectively, p < 0.05). This observational study establishes the ability of 19F MRI and 1H UTE MRI to detect improvements in lung structure and function after E/T/I treatment. This study supports further development of 19F MRI and 1H UTE MRI as outcome measures for cystic fibrosis research and drug development.

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Section: Discussionsupporting

confidence: 93%

Dynamic Perfluorinated Gas MRI Shows Improved Lung Ventilation in People with Cystic Fibrosis after Elexacaftor/Tezacaftor/Ivacaftor: An Observational Study

Goralski

Chung

Ceppe

et al. 2022

JCM

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“…Furthermore, MRI was more sensitive than forced expiratory volume in the 1st second (FEV 1 ) in detecting a response to CFTR modulator therapy [ 5 ]. Recently, improvements in chest MRI after 4 [ 6 ] or 8–16 weeks [ 7 ] of Trikafta ® (a triple combination of two correctors, Elexacaftor (ELX) and Tezacaftor (TEZ)), together with the potentiator IVA, were reported in adults with CF, demonstrating the reversibility of structural lung and paranasal sinus abnormalities in patients with established disease [ 6 , 7 ].…”

mentioning

confidence: 99%

Early Effects of Elexacaftor-Tezacaftor-Ivacaftor Therapy on Magnetic Resonance Imaging in Patients with Cystic Fibrosis and Advanced Lung Disease

Macconi

Galici

Maurizio

et al. 2022

JCM

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This is a prospective, observational study involving three Cystic Fibrosis (CF) adult patients, evaluating the changes in chest magnetic resonance imaging (MRI) three months after the start of elexacaftor/tezacaftor and ivacaftor therapy. MRI showed a drastic reduction in mucus plugging and bronchial wall thickening, with an improvement in the diffusion-weighted MRI score. Similarly, a marked improvement in spirometric parameters, nutritional status, and sweat chloride was observed. Our preliminary data confirm that chest MRI could be a useful tool to assess disease progression in CF patients on modulatory drug therapy.

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“…Paranasal sinus MRI also indicated a reduction in symptoms due to decreased abnormalities in mucopyoceles in the maxillary and ethmoid sinuses by ETI therapy. 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 ].…”

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

confidence: 86%

“…Data from 43 adults with CF carrying at least one F508del-CFTR allele were included in a retrospective, observational study to evaluate chest MRI scores and chronic rhinosinusitis–MRI scores before and after the start of ETI therapy [ 64 ]. Nineteen individuals were receiving ETI therapy, while 24 individuals were stable controls and received only standard treatment without CFTR modulators.…”

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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Magnetic resonance imaging detects improvements of pulmonary and paranasal sinus abnormalities in response to elexacaftor/tezacaftor/ivacaftor therapy in adults with cystic fibrosis

Cited by 44 publications

References 26 publications

Dynamic Perfluorinated Gas MRI Shows Improved Lung Ventilation in People with Cystic Fibrosis after Elexacaftor/Tezacaftor/Ivacaftor: An Observational Study

Dynamic Perfluorinated Gas MRI Shows Improved Lung Ventilation in People with Cystic Fibrosis after Elexacaftor/Tezacaftor/Ivacaftor: An Observational Study

Early Effects of Elexacaftor-Tezacaftor-Ivacaftor Therapy on Magnetic Resonance Imaging in Patients with Cystic Fibrosis and Advanced Lung Disease

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

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