Reversing the irreversible: Another potential benefit of CFTR modulators

Wright, Brittany A.; Cannon, Megan E.; Ramsey, Laura J.

doi:10.1002/ppul.25047

Cited by 5 publications

(5 citation statements)

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“…Data have also begun to surface regarding the extrapulmonary effects of CFTR modulator therapy, specifically elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA, Trikafta® Vertex Pharmaceuticals Incorporated) 10,11 . Previous reports suggest that ivacaftor has the potential to restore pancreatic duct function, which could improve pancreatic enzyme secretion, and in turn, absorption 12–16 …”

Section: Introductionmentioning

confidence: 99%

“…10,11 Previous reports suggest that ivacaftor has the potential to restore pancreatic duct function, which could improve pancreatic enzyme secretion, and in turn, absorption. [12][13][14][15][16] The primary objective of this study was to determine if the addition of ELX/TEZ/IVA resulted in improved vitamin D absorption as measured by serum 25-hydroxyvitamin D concentration.…”

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confidence: 99%

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Impact of elexacaftor/tezacaftor/ivacaftor on vitamin D absorption in cystic fibrosis patients

Wright

Ketchen

Rasmussen

et al. 2021

Pediatric Pulmonology

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Background: Cystic fibrosis (CF) is a multisystem disorder that results in the buildup of mucus in various organs. Ninety percent of CF patients are classified as pancreatic insufficient, leading to malabsorption of nutrients and fat-soluble vitamins without the assistance of exogenous pancreatic enzymes. This study was designed to determine if serum 25-hydroxyvitamin D concentrations were impacted by initiation of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA). Methods: Serum 25-hydroxyvitamin D concentrations were measured before and 1 year post-ELX/TEZ/IVA initiation. A Wilcoxon signed-rank test was used to compare values.Results: Seventy-six patients were included in the final analysis. The average age of our population was 25.8 years (SD = 13.2 years) with a majority being male, homozygous F508del, pancreatic insufficient, and not modulator-naive. The median increase of serum vitamin D concentration after initiating ELX/TEZ/IVA was 5 ng/ml (interquartile range = −4, 13; p = .0035). Conclusions:We suggest that ELX/TEZ/IVA may improve fat-soluble vitamin absorption, specifically serum 25-hydroxyvitamin D. These results may lead to adjustments in vitamin supplementation in patients receiving cystic fibrosis transmembrane conductance regulator modulator therapy.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Impact of elexacaftor/tezacaftor/ivacaftor on vitamin D absorption in cystic fibrosis patients

Wright

Ketchen

Rasmussen

et al. 2021

Pediatric Pulmonology

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“…Those who achieved pancreatic sufficient levels were more likely to have had detectable FE at baseline (8 of 11 vs. 0 of 7, p < .01), less likely to have a second severe mutation (F508del or minimal function: 2 of 11 vs. 6 of 7, p = .01), and more likely to be younger upon starting iva (4 vs. 8.6 years, p < .001) 23 . Several case reports published in 2020 also note improvements in pancreatic exocrine function in older children following use of CFTR modulators 24–26 (Table 2). Adult studies have not yet shown improvements in pancreatic function on CFTR modulators, so it unlikely that adults can achieve pancreatic sufficiency if started on modulators later in life.…”

Section: Other Clinical Parametersmentioning

confidence: 96%

“…In the study of lum/iva performed in the Netherlands in PwCF over age 6 years with FEV1pp ≥ 90%, 5 likely to be younger upon starting iva (4 vs. 8.6 years, p < .001). 23 Several case reports published in 2020 also note improvements in pancreatic exocrine function in older children following use of CFTR modulators [24][25][26] (Table 2). Adult studies have not yet shown improvements in pancreatic function on CFTR modulators, so it unlikely that adults can achieve pancreatic sufficiency if started on modulators later in life.…”

Section: Growth and Nutritionmentioning

confidence: 99%

Review of CFTR modulators 2020

Goetz

Savant

2021

Pediatric Pulmonology

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Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are small molecules that directly impact the CFTR protein, improving the function of the CFTR chloride and bicarbonate channel. Beginning in 2012 with the Food and Drug Administration approval of the first CFTR modulator, ivacaftor, this class of medications has had largely positive effects on many outcomes in people with cystic fibrosis (PwCF), including lung function, growth, and other clinical parameters. There have been continued exciting developments in the current research on CFTR modulators, expanding beyond original studies. This first part of a three-part cystic fibrosis (CF) year in review 2020 will focus on research on CFTR modulators. In addition to reviewing new clinical insights, we describe work done on novel outcomes, adverse effects, issues related to cost, and next steps for clinical trials. The review focuses on articles from Pediatric Pulmonology published in 2020, but it includes articles from other journals that are of particular interest to clinicians. New developments in CF research continue to be brought forth to the CF community, deepening the understanding of this disease and improving clinical care.

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“…Individual cases of improved pancreatic function in patients treated with lumacaftor/ivacaftor have been presented, mostly in case reports [21][22][23]. A clinical trial in patients 2-5 years of age showed a mean absolute change in FE-1 by 52.6 μg/g [24].…”

Section: Impact Of Cftr Modulator Therapy On Exocrine Pancreatic Func...mentioning

confidence: 99%

Improved Nutritional Outcomes and Gastrointestinal Symptoms in Adult Cystic Fibrosis Patients Treated with Elexacaftor/Tezacaftor/Ivacaftor

Stastna,

Kunovsky,

Svoboda

et al. 2024

Dig Dis

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Introduction: Cystic fibrosis transmembrane conductance regulator modulator therapy improves nutritional status and quality of life. Clinical trials have shown pancreatic insufficiency conversion, mostly in pediatric patients treated with ivacaftor. Studies with elexacaftor/tezacaftor/ivacaftor (ETI) in older patients have not suggested restoration of exocrine pancreas function, but quality data in adults are lacking. Our aim was to show the effect of ETI in adults with cystic fibrosis (CF) on nutritional status and digestive function. We hypothesized improvement of nutritional parameters and gastrointestinal symptoms, reduction of pancreatic enzyme replacement therapy, but uncertain improvement in exocrine pancreatic function. Methods: We prospectively enrolled adults with CF treated with ETI from August 2021 to June 2022. We measured anthropometric parameters, laboratory nutritional markers, change of fecal elastase, pancreatic enzymes replacement therapy needs, and gastrointestinal symptoms. Results: In the cohort of 29 patients (mean age 29.1 years), 82.8% suffered exocrine pancreatic insufficiency. After ETI, mean BMI increased by 1.20 kg/m2 (p < 0.001), mean body weight by 3.51 kg (p < 0.001), albumin by 2.81 g/L, and prealbumin by 0.06 (both p < 0.001). Only 1 patient, initially pancreatic insufficient (4.5%, p < 0.001), developed pancreatic sufficiency, indicated by increased fecal elastase from 45 μg/g to 442.1 μg/g. Mean change in lipase substitution decreased by 1,969 units/kg/day (p < 0.001) and stools frequency by 1.18 per day (p < 0.001). Conclusion: Our data suggest increased nutritional parameters, lower pancreatic substitution requirements, and improved defecation in adult CF patients on ETI. Improvement in exocrine pancreatic function might be mutation-specific and needs further study.

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Reversing the irreversible: Another potential benefit of CFTR modulators

Cited by 5 publications

References 5 publications

Impact of elexacaftor/tezacaftor/ivacaftor on vitamin D absorption in cystic fibrosis patients

Impact of elexacaftor/tezacaftor/ivacaftor on vitamin D absorption in cystic fibrosis patients

Review of CFTR modulators 2020

Improved Nutritional Outcomes and Gastrointestinal Symptoms in Adult Cystic Fibrosis Patients Treated with Elexacaftor/Tezacaftor/Ivacaftor

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