Elexacaftor - Tezacaftor - Ivacaftor Treatment Improves Systemic Infection Parameters and Colonization Rate in Patients with Cystic Fibrosis a Monocentric Observational Study

Overview

Journal Heliyon

Specialty Social Sciences

Date 2023 May 8

PMID 37153441

Authors

Alexander Schnell

Hannah Hober

Natalie Kaiser

Renate Ruppel

Annika Geppert

Christina Tremel

Julia Sobel

Erika Plattner

Joachim Woelfle

Andre Hoerning

Affiliations

Soon will be listed here.

Abstract

Background & Aims: The CFTR-modulating therapy Elexaftor - Tezacaftor - Ivacaftor (ETI) has been widely prescribed since its approval in 2020 in the European Union. The aim of this study was to methodically evaluate the effects of an ETI treatment on clinical, biochemical data and Pseudomonas colonization in order to demonstrate its efficacy.

Methods: This prospective monocentric study comprised 69 patients diagnosed with cystic fibrosis aged at least 12 years and treated with ETI between September 2020 and November 2021. Clinical and laboratory data of each patient and study visit were collected before and after 24 weeks of ETI treatment. Follow-up status of (PsA) colonization was assessed after one year of therapy by regularly determined sputum or throat swab samples.

Results: Marked improvements biochemical markers of systemic inflammation as white blood cell count, levels of immunoglobulins A, G and M and albumin within 24 weeks of therapy were observed. ETI treatment proved to be effective as seen by amelioration of lung function and sweat chloride concentration. Assessment of PsA colonization status revealed a conversion from a positive to negative detection in 36% of the cases after one year of therapy.

Conclusions: ETI treatment effectively improves systemic inflammation parameters and shows promising results in PsA status conversion.

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References

Sosinski L, Martin H C, Neugebauer K, Ghuneim L, Guzior D, Castillo-Bahena A . A restructuring of microbiome niche space is associated with Elexacaftor-Tezacaftor-Ivacaftor therapy in the cystic fibrosis lung. J Cyst Fibros. 2021; 21(6):996-1005. PMC: 9124239. DOI: 10.1016/j.jcf.2021.11.003. View

Laselva O, Bartlett C, Gunawardena T, Ouyang H, Eckford P, Moraes T . Rescue of multiple class II CFTR mutations by elexacaftor+tezacaftor+ivacaftor mediated in part by the dual activities of elexacaftor as both corrector and potentiator. Eur Respir J. 2020; 57(6). PMC: 8209484. DOI: 10.1183/13993003.02774-2020. View

Hall G, Filipow N, Ruppel G, Okitika T, Thompson B, Kirkby J . Official ERS technical standard: Global Lung Function Initiative reference values for static lung volumes in individuals of European ancestry. Eur Respir J. 2021; 57(3). DOI: 10.1183/13993003.00289-2020. View

Polverino F, Lu B, Quintero J, Vargas S, Patel A, Owen C . CFTR regulates B cell activation and lymphoid follicle development. Respir Res. 2019; 20(1):133. PMC: 6604167. DOI: 10.1186/s12931-019-1103-1. View

McBennett K, Davis P, Konstan M . Increasing life expectancy in cystic fibrosis: Advances and challenges. Pediatr Pulmonol. 2021; 57 Suppl 1:S5-S12. PMC: 9004282. DOI: 10.1002/ppul.25733. View

Ratjen F, Doring G . Cystic fibrosis. Lancet. 2003; 361(9358):681-9. DOI: 10.1016/S0140-6736(03)12567-6. View

Ramsey B, Davies J, McElvaney N, Tullis E, Bell S, Drevinek P . A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011; 365(18):1663-72. PMC: 3230303. DOI: 10.1056/NEJMoa1105185. View

Tiringer K, Treis A, Fucik P, Gona M, Gruber S, Renner S . A Th17- and Th2-skewed cytokine profile in cystic fibrosis lungs represents a potential risk factor for Pseudomonas aeruginosa infection. Am J Respir Crit Care Med. 2013; 187(6):621-9. DOI: 10.1164/rccm.201206-1150OC. View

Graeber S, Boutin S, Wielputz M, Joachim C, Frey D, Wege S . Effects of Lumacaftor-Ivacaftor on Lung Clearance Index, Magnetic Resonance Imaging, and Airway Microbiome in Phe508del Homozygous Patients with Cystic Fibrosis. Ann Am Thorac Soc. 2021; 18(6):971-980. DOI: 10.1513/AnnalsATS.202008-1054OC. View

10.

Nichols D, Paynter A, Heltshe S, Donaldson S, Frederick C, Freedman S . Clinical Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor in People with Cystic Fibrosis: A Clinical Trial. Am J Respir Crit Care Med. 2021; 205(5):529-539. PMC: 8906485. DOI: 10.1164/rccm.202108-1986OC. View

11.

Middleton P, Mall M, Drevinek P, Lands L, McKone E, Polineni D . Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019; 381(19):1809-1819. PMC: 7282384. DOI: 10.1056/NEJMoa1908639. View

12.

Robledo-Avila F, Ruiz-Rosado J, Brockman K, Kopp B, Amer A, McCoy K . Dysregulated Calcium Homeostasis in Cystic Fibrosis Neutrophils Leads to Deficient Antimicrobial Responses. J Immunol. 2018; 201(7):2016-2027. PMC: 6143431. DOI: 10.4049/jimmunol.1800076. View

13.

McKone E, Ariti C, Jackson A, Zolin A, Carr S, Orenti A . Survival estimates in European cystic fibrosis patients and the impact of socioeconomic factors: a retrospective registry cohort study. Eur Respir J. 2021; 58(3). DOI: 10.1183/13993003.02288-2020. View

14.

Hector A, Schafer H, Poschel S, Fischer A, Fritzsching B, Ralhan A . Regulatory T-cell impairment in cystic fibrosis patients with chronic pseudomonas infection. Am J Respir Crit Care Med. 2015; 191(8):914-23. DOI: 10.1164/rccm.201407-1381OC. View

15.

Ratner D, Mueller C . Immune responses in cystic fibrosis: are they intrinsically defective?. Am J Respir Cell Mol Biol. 2012; 46(6):715-22. DOI: 10.1165/rcmb.2011-0399RT. View

16.

Favia M, Gallo C, Guerra L, De Venuto D, Diana A, Polizzi A . Treatment of Cystic Fibrosis Patients Homozygous for with Lumacaftor-Ivacaftor (Orkambi) Restores Defective CFTR Channel Function in Circulating Mononuclear Cells. Int J Mol Sci. 2020; 21(7). PMC: 7177453. DOI: 10.3390/ijms21072398. View

17.

Morrison C, Shaffer K, Araba K, Markovetz M, Wykoff J, Quinney N . Treatment of cystic fibrosis airway cells with CFTR modulators reverses aberrant mucus properties hydration. Eur Respir J. 2021; 59(2). PMC: 8859811. DOI: 10.1183/13993003.00185-2021. View

18.

Bratcher P, Rowe S, Reeves G, Roberts T, Szul T, Harris W . Alterations in blood leukocytes of G551D-bearing cystic fibrosis patients undergoing treatment with ivacaftor. J Cyst Fibros. 2015; 15(1):67-73. PMC: 4567518. DOI: 10.1016/j.jcf.2015.02.010. View

19.

Ronan N, Einarsson G, Twomey M, Mooney D, Mullane D, NiChroinin M . CORK Study in Cystic Fibrosis: Sustained Improvements in Ultra-Low-Dose Chest CT Scores After CFTR Modulation With Ivacaftor. Chest. 2017; 153(2):395-403. DOI: 10.1016/j.chest.2017.10.005. View

20.

Petersen M, Begnel L, Wallendorf M, Litvin M . Effect of elexacaftor-tezacaftor-ivacaftor on body weight and metabolic parameters in adults with cystic fibrosis. J Cyst Fibros. 2021; 21(2):265-271. PMC: 9999463. DOI: 10.1016/j.jcf.2021.11.012. View