title: Ivacaftor as salvage therapy in a patient with cystic fibrosis genotype F508del/R117H/IVS8-5T.
abstract: Ivacaftor is a novel CFTR potentiator that increases CFTR activity and improves clinical outcomes in cystic fibrosis (CF) patients with at least one copy of CFTR-G551D. Clinical trials have shown an improvement in lung function, weight and CF pulmonary exacerbation in adults with CFTR-G551D leading to the approval of ivacaftor as a novel CF therapy [1]. In vitro studies of ivacaftor have also shown significant improvements in CFTR chloride channel opening time in other non-G551D CFTR mutations suggesting that ivacaftor may be of benefit to patients with mutations other than gating mutations [2]. R117H-CFTR is a relatively common CFTR mutation that demonstrates an in-vitro response to ivacaftor [2,3]. A clinical trial has suggested that there may be a role for ivacaftor in older patients with R117H-CFTR although this trial did not include patients with very severe CF lung disease [4]. In 2014, ivacaftor was approved in the United States as a treatment for CF subjects aged greater than 6 years old with a copy of R117H-CFTR. We present a case demonstrating a substantial therapeutic effect of ivacaftor in a CF patient with genotype F508del/R117H and advanced lung disease.
authors.affiliation: National Referral Centre for Adult Cystic Fibrosis, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: Carter
authors.affiliation: National Referral Centre for Adult Cystic Fibrosis, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: Kelly
authors.affiliation: National Referral Centre for Adult Cystic Fibrosis, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
authors.forename: E
authors.initials: E
authors.lastname: Caples
authors.affiliation: National Referral Centre for Adult Cystic Fibrosis, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
authors.forename: B
authors.initials: B
authors.lastname: Grogan
authors.affiliation: National Referral Centre for Adult Cystic Fibrosis, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
authors.forename: J
authors.initials: J
authors.lastname: Doyle
authors.affiliation: National Referral Centre for Adult Cystic Fibrosis, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
authors.forename: C G
authors.initials: CG
authors.lastname: Gallagher
authors.affiliation: National Referral Centre for Adult Cystic Fibrosis, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
authors.forename: E F
authors.initials: EF
authors.lastname: McKone
mesh_terms: D000627:Aminophenols / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000627:therapeutic use*; D016879:Salvage Therapy
chemical_list: D000627:Aminophenols; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor
keywords: CFTR corrector therapy; CFTR genotype; Pharmacogenetics