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. 2020 Aug 16;21(16):5882.
doi: 10.3390/ijms21165882.

From Ivacaftor to Triple Combination: A Systematic Review of Efficacy and Safety of CFTR Modulators in People with Cystic Fibrosis

Andrea Gramegna  1   2 , Martina Contarini  2 , Stefano Aliberti  1   2 , Rosaria Casciaro  3 , Francesco Blasi  1   2 , Carlo Castellani  3
Affiliations

From Ivacaftor to Triple Combination: A Systematic Review of Efficacy and Safety of CFTR Modulators in People with Cystic Fibrosis

Andrea Gramegna et al. Int J Mol Sci. .

Abstract

Over the last years CFTR (cystic fibrosis transmembrane conductance regulator) modulators have shown the ability to improve relevant clinical outcomes in patients with cystic fibrosis (CF). This review aims at a systematic research of the current evidence on efficacy and tolerability of CFTR modulators for different genetic subsets of patients with CF. Two investigators independently performed the search on PubMed and included phase 2 and 3 clinical trials published in the study period 1 January 2005-31 January 2020. A final pool of 23 papers was included in the systematic review for a total of 4219 patients. For each paper data of interest were extracted and reported in table. In terms of lung function, patients who had the most beneficial effects from CFTR modulation were those patients with one gating mutation receiving IVA (ivacaftor) and patients with p.Phe508del mutation, both homozygous and heterozygous, receiving ELX/TEZ/IVA (elexacaftor/tezacaftor/ivacaftor) had the most relevant beneficial effects in term of lung function, pulmonary exacerbation decrease, and symptom improvement. CFTR modulators showed an overall favorable safety profile. Next steps should aim to systematize our comprehension of scientific data of efficacy and safety coming from real life observational studies.

Keywords: CFTR modulators; clinical efficacy; cystic fibrosis; safety.

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Conflict of interest statement

A.G. reports grant support and consultancy fees from Vertex Pharmaceuticals; fees from Grifols, Insmed and Chiesi Pharmaceuticals. S.A. reports grant funding or fees for consultancy from Astrazeneca, Boehringer-Ingelheim, Gilead, Glaxosmithkline, Grifols, Insmed and Zambon. R.C. reports consultancy fees from Vertex Pharmaceuticals, Gilead and Chiesi Pharmaceuticals. F.B. reports grants and consultancy fees from Astrazeneca, Bayer, Chiesi Pharmaceuticals, Insmed, Pfizer; consultancy fees from GSK, Guidotti and Grifols, Mundipharma, Vertex Pharmaceuticals, Zambon. C.C. reports consultancy fees from Vertex Pharmaceuticals, Gilead, Mylan Pharmaceutical Industries, Actelion Pharmaceuticals, and Chiesi Pharmaceuticals. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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Figure 1
Flow chart of the systematic review.
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References

    1. Bell S.C., Mall M.A., Gutierrez H., Macek M., Madge S., Davies J.C., Burgel P.-R., Tullis E., Castaños C., Castellani C., et al. The future of cystic fibrosis care: A global perspective. Lancet Respir. Med. 2020;8:65–124. doi: 10.1016/S2213-2600(19)30337-6. - DOI - PMC - PubMed
    1. Riordan J.R., Rommens J.M., Kerem B., Alon N., Rozmahel R., Grzelczak Z., Zielenski J., Lok S., Plavsic N., Chou J.L., et al. Identification of the cystic fibrosis gene: Cloning and characterization of complementary DNA. Science. 1989;245:1066–1073. doi: 10.1126/science.2475911. - DOI - PubMed
    1. Tsui L.C. The cystic fibrosis transmembrane conductance regulator gene. Am. J. Respir. Crit. Care Med. 1995;151:S47. doi: 10.1164/ajrccm/151.3_Pt_2.S47. - DOI - PubMed
    1. Donaldson S.H., Boucher R.C. Sodium channels and cystic fibrosis. Chest. 2007;132:1631–1636. doi: 10.1378/chest.07-0288. - DOI - PubMed
    1. Riordan J.R. Assembly of functional CFTR chloride channels. Annu. Rev. Physiol. 2005;67:701–718. doi: 10.1146/annurev.physiol.67.032003.154107. - DOI - PubMed

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