Highlights
- •While CFTR effect on lung function has been clearly reported, we are still in the process of unraveling the full impact they have on the pancreas.
- •We suggest that highly effective modulator combination therapy may restore additional pancreatic acinar activity, resulting in the development of acute pancreatitis in the interim until ductal flow is improved.
- •This report adds to the growing evidence for possible restoration of pancreatic function in patients receiving modulator therapy, and highlights that treatment with elexacaftor/tezacaftor/ivacaftor may be associated with acute pancreatitis until ductal flow is restored, even in pancreatic-insufficient CF patients.
Abstract
Cystic fibrosis transmembrane conductance regulator modulator therapy is associated
with substantial clinical benefit and improved quality of life in patients with cystic
fibrosis (CF). While their effect on lung function has been clearly reported, we are
still in the process of unraveling the full impact they have on the pancreas. We present
two cases of pancreatic-insufficient CF patients who presented with acute pancreatitis
shortly after commencing elexacaftor/tezacaftor/ivacaftor modulator therapy. Both
patients were treated with ivacaftor for 5 years prior to elexacaftor/tezacaftor/ivacaftor
initiation, but had no previous episodes of acute pancreatitis.
We suggest that highly effective modulator combination therapy may restore additional
pancreatic acinar activity, resulting in the development of acute pancreatitis in
the interim until ductal flow is improved. This report adds to the growing evidence
for possible restoration of pancreatic function in patients receiving modulator therapy,
and highlights that treatment with elexacaftor/tezacaftor/ivacaftor may be associated
with acute pancreatitis until ductal flow is restored, even in pancreatic-insufficient
CF patients.
Keywords
Abbreviations:
AP (acute pancreatitis), CF (cystic fibrosis), CFTR (cystic fibrosis transmembrane conductance regulator), ELE/TEZ/IVA (elexacaftor/tezacaftor/ivacaftor), PI (pancreatic insufficient)To read this article in full you will need to make a payment
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References
- Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele.N Engl J Med. 2019; 381: 1809-1819
- Pancreatitis in a patient with cystic fibrosis taking ivacaftor.Children (Basel). 2020; 7
- CFTR modulators increase risk of acute pancreatitis in pancreatic insufficient patients with cystic fibrosis.J Cyst Fibros. 2021;
- Time for a gut check: pancreatic sufficiency resulting from CFTR modulator use.Pediatr Pulmonol. 2019; 54: E16-E18
- Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in pancreatitis.J Cyst Fibros. 2012; 11: 355-362
- Cystic fibrosis transmembrane conductance regulator modulators reduce the risk of recurrent acute pancreatitis among adult patients with pancreas sufficient cystic fibrosis.Pancreatology. 2019; 19: 1023-1026
- Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study.Lancet Respir Med. 2016; 4: 107-115
- Ivacaftor treatment of cystic fibrosis in children aged 12 to <24 months and with a CFTR gating mutation (ARRIVAL): a phase 3 single-arm study.Lancet Respir Med. 2018; 6: 545-553
- An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2-5 years (KLIMB).J Cyst Fibros. 2019; 18: 838-843
- GP284 The effects of ivacaftor on pancreatic function in paediatric patients with cystic fibrosis gating mutations.Arch Dis Child. 2019; 104 (2019:): A149-A150
- Restoration of exocrine pancreatic function in older children with cystic fibrosis on ivacaftor.Paediatr Respir Rev. 2020; 35: 99-102
Article info
Publication history
Published online: March 11, 2023
Accepted:
February 27,
2023
Received in revised form:
January 31,
2023
Received:
November 23,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
