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.