Corresponding author
Name: Dr. Rachael Marpole
Mailing address: Respiratory and Sleep Medicine Department, Perth
Children’s Hospital, 15 Hospital Avenue, Locked Bag 2010, Nedlands WA
6009, Australia.
Phone number: +61 8 6456 2222
Email: rachael.marpole@health.wa.gov.au
ORCID Rachael Marpole
https://orcid.org/0000-0002-2652-0560
Key words Cystic fibrosis, Pancreatic function, CFTR
modulators, residual CFTR function, child, paediatric
Running head: Reviewing pancreatic function in CF
To the Editor,
Cystic fibrosis (CF) is a common autosomal recessive disease that causes
pancreatic exocrine insufficiency (PI) in 90% of
cases1. Over the last decade new CF transmembrane
conductance regulator (CFTR) protein modulator therapies, like
ivacaftor, have become available. Ivacaftor can cause children with a
gating mutation, up to 14 years of age, born with a meconium ileus to
become pancreatic exocrine sufficient (PS)2. Of note,
children with residual CFTR function mutations may be PI in infancy and
then spontaneously become PS3.
Current recommendations from the Nutrition guidelines for CF in
Australia and New Zealand suggest all children with CF have pancreatic
function tested at diagnosis1. It is also suggested
that repeat testing can help guide pancreatic enzymes replacement
therapy (PERT) in patients on CF modulators. The aim of this study was
to evaluate the benefit of reviewing pancreatic function testing and
diagnosis of PS/PI of a cohort of CF patients and offering repeat
testing to patients who had potential to become PS since initial
testing.
Institutional ethics approval was granted prior to commencement of the
study. All children with CF living in Western Australia were included.
Retrospective review of the following included age, sex, birthplace,
genotype, eligibility for and prescription of modulator therapy, current
pancreatic function status, previous testing, meconium ileus at birth,
and if prescribed PERT. After review, patients who had potential to
become PS were offered testing prospectively.
There was 204 children and adolescents with CF being managed at Perth
Children’s Hospital the only tertiary paediatric hospital in Western
Australia, at the end of 2019. 95 (46%) were males, with an age range
of 0-18 years. Exocrine pancreatic function had been tested in 177/204
(86%), with the majority having faecal pancreatic elastase testing. Out
of the tested cohort 73% were diagnosed as PI (130/177).
Ivacaftor
All 12 patients eligible for ivacaftor were pancreatic insufficient, 11
were on PERT (table 1). One patient ceased ivacaftor due to poor
tolerance. All taking ivacaftor were offered repeat testing. 81% (9/11)
completed this. Four had become PS since starting ivacaftor (one
clinically), with three stopping PERT. Two of the three patients
experienced recurrent abdominal pain when taking PERT, which resolved on
ceasing. Time on ivacaftor to stopping PERT varied from 14 months to 3
years. Age at stopping was 5, 9 and 10 years. One infant who tested
initially as PI was not started on PERT due to lack of symptoms of
malabsorption, became PS after six months of ivacaftor.
Other patients continue to be PI and on PERT despite being prescribed
ivacaftor for up to 8 years. This includes an adolescent who developed
pancreatitis twice after being on ivacaftor for 6 years. His pancreatic
elastase has increased from <15 to 120microg/g.