Abstract
Substantial progress has been made in the treatment of Cystic fibrosis due to introduction of CFTR modulators. However, little is known about the long term side effects of treatment with these drugs. We here present a 7 year old girl with CF who presented with breast development as a rare dose dependent side effect of treatment with ivacaftor and we report data on the correlation between drug plasma concentration and clinical effect, bodyweight, and BSA in 16 patients.Higher plasma concentrations did not correlate with clinical effect, as change in FEV1 and sweat chloride concentration. Patients with low bodyweight or BSA tended to have higher plasma concentrations. This might indicate that the current recommended dose of ivacaftor is at the top of the dose-response curve and that some patients can be treated with lower doses of ivacaftor with similar clinical effect.
Highlights
Treatment of patients with Cystic Fibrosis (CF) has been challenging for decades, but Cystic Fibrosis Transmembrane conductance Regulator (CFTR) modulators such as ivacaftor, lumacaftor, tezacaftor and lately elexacaftor impressively changed the perspectives [1,2]
Treatment with Cystic fibrosis transmembrane conductance regulator (CFTR) modulators started in adults and children aged 12 years and older, but treatment is becoming available to younger children from the age of 6 months [3,4,5]
No breast development was observed until now after being treated with this dose for 17 months. In this case the appearance of premature telarche seems to be related to the dose of ivacaftor. Based on these findings we studied the relation between the plasma concentration of ivacaftor and a patient’s weight and clinical effect to treatment, in a group of patients that was treated with ivacaftor
Summary
Treatment of patients with Cystic Fibrosis (CF) has been challenging for decades, but Cystic Fibrosis Transmembrane conductance Regulator (CFTR) modulators such as ivacaftor, lumacaftor, tezacaftor and lately elexacaftor impressively changed the perspectives [1,2]. Treatment with CFTR modulators started in adults and children aged 12 years and older, but treatment is becoming available to younger children from the age of 6 months [3,4,5]. A CFTR-potentiator, is prescribed in adults and children aged 6 years and older with a body weight above 25 kgs (kg) in a dose of 300 mg /day (mg/day). Little research is available on the optimal dose for younger children. Davies et al [3] and Rosenfeld et al [4] treated children aged 2–5 years and 1,2 years, respectively, with 100–150 mg/day. No data is available on the effect of lower doses of ivacaftor in these young children
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