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Ivacaftor response

MedGen UID:
776837
Concept ID:
CN185459
Sign or Symptom
Synonym: Kalydeco response
Drug:
Ivacaftor
MedGen UID:
471967
Concept ID:
C3264621
Organic Chemical
 
Gene (location): CFTR (7q31.2)

Definition

Ivacaftor is the first FDA-approved drug designed to target a specific defect of the CFTR protein found in a subset of Cystic fibrosis (CF) patients. Hundreds of different variants within the CFTR gene have been identified. The G551D variant (rs75527207 G>A) results in defective gating at the plasma membrane and, in combination with another disease-causing CFTR allele, can result in CF disease phenotypes. Ivacaftor is designed to potentiate G115D-CFTR to improve symptoms in CF patients who carry this variant. Therapeutic guidelines for ivacaftor based on CFTR genotype have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website. [from PharmGKB]

Professional guidelines

PubMed

Lefferts JW, Bierlaagh MC, Kroes S, Nieuwenhuijze NDA, Sonneveld van Kooten HN, Niemöller PJ, Verburg TF, Janssens HM, Muilwijk D, van Beuningen SFB, van der Ent CK, Beekman JM
Int J Mol Sci 2023 Sep 26;24(19) doi: 10.3390/ijms241914539. PMID: 37833986Free PMC Article
Paterson SL, Barry PJ, Horsley AR
Expert Rev Respir Med 2020 Jan;14(1):15-30. Epub 2019 Oct 31 doi: 10.1080/17476348.2020.1682998. PMID: 31626570
Turnbull AR, Davies JC
Expert Opin Pharmacother 2016 Jun;17(8):1103-12. Epub 2016 Mar 28 doi: 10.1517/14656566.2016.1157582. PMID: 27017976

Recent clinical studies

Therapy

Raraigh KS, Paul KC, Goralski JL, Worthington EN, Faino AV, Sciortino S, Wang Y, Aksit MA, Ling H, Osorio DL, Onchiri FM, Patel SU, Merlo CA, Montemayor K, Gibson RL, West NE, Thakerar A, Bridges RJ, Sheppard DN, Sharma N, Cutting GR
JCI Insight 2022 Mar 22;7(6) doi: 10.1172/jci.insight.148841. PMID: 35315358Free PMC Article
Arora K, Yang F, Brewington J, McPhail G, Cortez AR, Sundaram N, Ramananda Y, Ogden H, Helmrath M, Clancy JP, Naren AP
Am J Physiol Gastrointest Liver Physiol 2021 Jun 1;320(6):G1123-G1130. Epub 2021 May 5 doi: 10.1152/ajpgi.00095.2021. PMID: 33949881Free PMC Article
Fidler MC, Buckley A, Sullivan JC, Statia M, Boj SF, Vries RGJ, Munck A, Higgins M, Moretto Zita M, Negulescu P, van Goor F, De Boeck K
Clin Transl Sci 2021 Mar;14(2):656-663. Epub 2020 Dec 6 doi: 10.1111/cts.12927. PMID: 33278322Free PMC Article
Kopp BT, McCulloch S, Shrestha CL, Zhang S, Sarzynski L, Woodley FW, Hayes D Jr
Pediatr Pulmonol 2018 May;53(5):583-591. Epub 2018 Feb 20 doi: 10.1002/ppul.23972. PMID: 29461009
McGarry ME, Illek B, Ly NP, Zlock L, Olshansky S, Moreno C, Finkbeiner WE, Nielson DW
Pediatr Pulmonol 2017 Apr;52(4):472-479. Epub 2017 Jan 9 doi: 10.1002/ppul.23659. PMID: 28068001Free PMC Article

Prognosis

Santos LG, Pereira SV, Kmit AHP, Bonadia LC, Bertuzzo CS, Ribeiro JD, Mazzola TN, Marson FAL
Gene 2023 Jun 30;871:147428. Epub 2023 Apr 15 doi: 10.1016/j.gene.2023.147428. PMID: 37068695
McGarry ME, Illek B, Ly NP, Zlock L, Olshansky S, Moreno C, Finkbeiner WE, Nielson DW
Pediatr Pulmonol 2017 Apr;52(4):472-479. Epub 2017 Jan 9 doi: 10.1002/ppul.23659. PMID: 28068001Free PMC Article

Clinical prediction guides

Santos LG, Pereira SV, Kmit AHP, Bonadia LC, Bertuzzo CS, Ribeiro JD, Mazzola TN, Marson FAL
Gene 2023 Jun 30;871:147428. Epub 2023 Apr 15 doi: 10.1016/j.gene.2023.147428. PMID: 37068695
Fidler MC, Buckley A, Sullivan JC, Statia M, Boj SF, Vries RGJ, Munck A, Higgins M, Moretto Zita M, Negulescu P, van Goor F, De Boeck K
Clin Transl Sci 2021 Mar;14(2):656-663. Epub 2020 Dec 6 doi: 10.1111/cts.12927. PMID: 33278322Free PMC Article
McGarry ME, Illek B, Ly NP, Zlock L, Olshansky S, Moreno C, Finkbeiner WE, Nielson DW
Pediatr Pulmonol 2017 Apr;52(4):472-479. Epub 2017 Jan 9 doi: 10.1002/ppul.23659. PMID: 28068001Free PMC Article

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