Residual CFTR function
Of the 35 patients with at least one residual CFTR function mutation, 29 have had pancreatic elastase above 200mcg/g since diagnosis and one had never been tested however was clinically PS. Two had previously become PS before the age of 2 years. The remaining three were offered retesting. All completed with two becoming PS at age 3 and 16 years. See table 2.
In this study there were three clear findings. Firstly, treatment with ivacaftor is associated with a change from PI to PS in children with gating mutations. There are two multicentred studies that review pancreatic function in children with gating mutations on ivacaftor4,5. They include 12-24-month-olds and 2-5-year-olds. After 24 weeks of ivacaftor 18-30% became PS. In our cohort 36% (4/11) became PS after starting ivacaftor. Children are more likely to change function if initial pancreatic elastase is more than 50microg/g and if ivacaftor is started at a younger age. Potentially children eligible for ivacaftor at one year of age with borderline pancreatic function can now be managed without PERT if growing well.
Secondly, children with PI and a residual CFTR function mutation can spontaneously become PS3. During this review,one patient with a residual CFTR function mutation continues to be PI. Most changed to PS prior to age 4 years and if their initial pancreatic elastase was over 150 micrograms/g.
Thirdly, new abdominal pain or constipation when taking PERT may be a sign of change in pancreatic function in children with the potential to change. 50% (2/4) of the children on ivacaftor experienced pain with PERT and one child with a residual CFTR function mutation became constipated prior to repeat testing. Acknowledging that abdominal pain and constipation can be common in cystic fibrosis patients. The limitations of this study are it is from a single centre. There are small numbers. Also, some results are limited by missing data especially in children who had moved to Western Australia.
The future of CF care is rapidly changing given the advancement of modulator therapy. Recurrent abdominal pain and constipation may be caused by improvement in pancreatic function. Regular reassessment of pancreatic function will prevent inappropriate PERT prescription and reduce side effects. Future research in this area should be included in multicentre phase 3 trials on new modulator treatment, especially if involving young children who are PI.
In children with CF, there is benefit to reviewing pancreatic function regularly, especially if on ivacaftor for a gating mutation, have residual CFTR function mutations or have new abdominal pain when taking PERT.