title: Ivacaftor treatment in patients with cystic fibrosis and the G551D-CFTR mutation.
abstract: Cystic fibrosis (CF) is an autosomal recessive lethal disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes for CFTR, an epithelial cell-surface expressed protein responsible for the transport of chloride (Cl(-)). Gating mutations associated with defective conductance can be modulated by CFTR potentiators. Ivacaftor is a CFTR potentiator approved for the treatment of CF patients >6 yrs of age with at least one copy of the G551D-CFTR mutation. Herein, the clinical trial development programme for ivacaftor will be reviewed, including two pivotal studies in adolescents/adults and in children. These studies report sustained improvements in lung function and sweat chloride concentrations, and a reduction in pulmonary exacerbations over a 48-week treatment period. In the era of personalised medicine, ivacaftor offers an effective and well-tolerated treatment for the clinical management of CF patients with the G551D mutation. A long-term, open-label study will report the effects of ivacaftor over a further 48 weeks.
authors: Centre de Ressources et de Compétences pour la Mucoviscidose, Hopital Necker-Enfants-Malades, INSERM U845, Université René Descartes, Paris, France. isabelle.sermet@nck.aphp.fr
authors: Isabelle
authors: I
authors: Sermet-Gaudelus
mesh_terms: D000293:Adolescent; D000328:Adult; D000627:Aminophenols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002712:Chlorides / Q000378:metabolism; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000819:agonists* / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D009154:Mutation; D018579:Patient Selection; D010641:Phenotype; D057285:Precision Medicine; D015363:Quinolones / Q000009:adverse effects / Q000627:therapeutic use*; D019141:Respiratory System Agents / Q000009:adverse effects / Q000627:therapeutic use*; D013542:Sweat / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000627:Aminophenols; C505032:CFTR protein, human; D002712:Chlorides; D015363:Quinolones; D019141:Respiratory System Agents; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor