Ivacaftor for the p.Ser549Arg (S549R) gating mutation - The Israeli experience

Adi Dagan; Malena Cohen-Cymberknoh; Michal Shteinberg; Hagit Levine; Daphna Vilozni; Yael Bezalel; Bat-El Bar Aluma; Ifat Sarouk; Moshe Ashkenazi; Moran Lavie; Reuven Tsabari; Hannah Blau; Eitan Kerem; Lea Bentur; Ori Efrati; Galit Livnat

doi:10.1016/j.rmed.2017.08.026

Ivacaftor for the p.Ser549Arg (S549R) gating mutation - The Israeli experience

Respir Med. 2017 Oct:131:225-228. doi: 10.1016/j.rmed.2017.08.026. Epub 2017 Sep 1.

Authors

Adi Dagan¹, Malena Cohen-Cymberknoh², Michal Shteinberg³, Hagit Levine⁴, Daphna Vilozni⁵, Yael Bezalel⁵, Bat-El Bar Aluma⁵, Ifat Sarouk⁵, Moshe Ashkenazi⁵, Moran Lavie⁵, Reuven Tsabari², Hannah Blau⁴, Eitan Kerem², Lea Bentur⁶, Ori Efrati⁵, Galit Livnat³

Affiliations

¹ Pediatric Pulmonary Unit and the National Center for Cystic Fibrosis, Edmond and Lili Safra Children's Hospital, Chaim Sheba Medical Center at Tel Hashomer, Affiliated with Sackler Medical School, Tel Aviv University, Israel. Electronic address: adi.dagan@sheba.health.gov.il.
² Cystic Fibrosis Center, Hebrew University Hadassah Medical Center, Jerusalem, Israel.
³ Cystic Fibrosis Center, Carmel Hospital, Ruth and Bruce Rappaport Faculty of Medicine, Technion - Institute of Technology, Haifa, Israel.
⁴ Graub Cystic Fibrosis Center, Schneider Children's Medical Center, Petach Tikva, Affiliated with Sackler Faculty of Medicine, Tel Aviv University, Israel.
⁵ Pediatric Pulmonary Unit and the National Center for Cystic Fibrosis, Edmond and Lili Safra Children's Hospital, Chaim Sheba Medical Center at Tel Hashomer, Affiliated with Sackler Medical School, Tel Aviv University, Israel.
⁶ Cystic Fibrosis Center, Rambam Health Care Campus, Haifa, Israel.

PMID: 28947035
DOI: 10.1016/j.rmed.2017.08.026

Abstract

Background: Ivacaftor is a drug that increases the probability of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel remaining open. Information about the efficacy of ivacaftor in patients carrying the rare p.Ser549Arg (S549R) CFTR mutation is sparse.

Aim: Efficacy of ivacaftor treatment in patients carrying the p.Ser549Arg (S549R) CFTR mutation.

Methods: Data obtained from CF patients receiving ivacaftor for one year.

Results: Eight CF patients, mean age 21 ± 10 years, received ivacaftor. After one year, significant improvement was found in FEV₁, increasing from 74% to 88% (p < 0.001), FVC, 89% to 101% (p = 0.019), and FEF_25-75, 59%-76% (p = 0.019). Sweat chloride concentration decreased from 116 ± 8 mmol/L to 51 ± 17 mmol/L (p < 0.001), and BMI increased from 20 ± 3 to 22 ± 4 (p = 0.003). Glucose tolerance improved in five patients. There was no significant change in bacterial colonization.

Conclusions: Ivacaftor therapy resulted in significant clinical improvement in patients carrying the p.Ser549Arg (S549R) CFTR mutation.

Keywords: Cystic fibrosis; Gating mutation; Ivacaftor; p.Ser549Arg (S549R).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aminophenols / therapeutic use*
Blood Glucose / metabolism
Body Mass Index
Child
Chloride Channel Agonists / therapeutic use*
Cohort Studies
Cystic Fibrosis / drug therapy*
Cystic Fibrosis / genetics
Cystic Fibrosis / metabolism
Cystic Fibrosis / physiopathology
Cystic Fibrosis Transmembrane Conductance Regulator / genetics
Female
Forced Expiratory Volume
Glucose Tolerance Test
Humans
Israel
Male
Mutation
Quinolones / therapeutic use*
Retrospective Studies
Sweat / chemistry
Treatment Outcome
Vital Capacity
Young Adult

Substances

Aminophenols
Blood Glucose
CFTR protein, human
Chloride Channel Agonists
Quinolones
Cystic Fibrosis Transmembrane Conductance Regulator
ivacaftor