Ivacaftor for cystic fibrosis

A 33 year old man with cystic fibrosis has come to discuss a new therapy for which he is eligible because of his genotype Phe508del/Gly551Asp. He has moderate lung function impairment with a forced expiratory volume in one second (FEV₁) of 67% of predicted, which has declined from 85% over the preceding five years. During this period, he has noted an increased requirement for intravenous antibiotics (two or three courses a year). In addition, he has pancreatic insufficiency, malnutrition (body mass index 17.5), recurrent constipation, and arthropathy which is disabling and worsens during periods of ill health. The patient is started on ivacaftor. Within a few days of starting therapy, he has noted an improvement in all his symptoms. His sputum has become easier to expectorate and is less in volume. Lung function measured at one month has increased by 15% over his baseline value.

Cystic fibrosis is an autosomal recessive genetic disorder affecting approximately 10 000 people in the UK and 30 000 in the US.12 Dysfunction or absence of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, an anion channel that sits on epithelial cell surfaces, leads to the clinical syndrome of cystic fibrosis. The most common and serious consequences are pulmonary disease, which is almost universal, and exocrine pancreatic insufficiency, which affects approximately 85% of patients).12 There is progressive decline in lung function punctuated by acute episodes with increased cough …