Time for a gut check: Pancreatic sufficiency resulting from CFTR modulator use

Abstract

Pancreatic exocrine insufficiency in cystic fibrosis is genetically determined and generally felt to be irreversible. However, recent studies in young children started on cystic fibrosis transmembrane conductance regulator (CFTR) modulators have suggested improvement of pancreatic functioning over time. Here, we present the case of a 10‐year‐old child with pancreatic exocrine insufficiency since birth who regained pancreatic functioning after 4 years on the CFTR corrector drug, ivacaftor.

Pancreatic insufficiency converted to pancreatic sufficiency with ivacaftor

“…Our experience mirrors that of Megalaa et al There is limited evidence that ivacaftor may be beneficial in preventing recurrent pancreatitis in patients with CF and one F508del mutation . However, we posit that ivacaftor may place children who convert from pancreatic insufficient to sufficient at risk for acute pancreatitis, due to increased pancreatic enzyme secretion without sustained commensurate improvements in pancreatic ductal secretion (water and bicarbonate).…”

“…We write in regard to the recently published case report “Time for a gut check: Pancreatic sufficiency resulting from CFTR modulator use,” which discusses the case of a ten‐year‐old boy who experienced recovery of exocrine pancreatic function 4 years after initiation of ivacaftor . This case is remarkably similar to a six‐year‐old female with cystic fibrosis (CF), genotype Phe508del/G551D , who we follow at our pediatric CF Center.…”

Reversing the irreversible: Another potential benefit of CFTR modulators

“…2 This damage was considered to be permanent and irreversible; however, recent publications have shown that this may not be the case. [3][4][5] While this response has been previously documented with ivacaftor monotherapy, we present this case of a pediatric CF patient who regained pancreatic function after initiation and use of lumacaftor/ivacaftor.…”

Cystic fibrosis year in review 2019: Section 1 CFTR modulators

“…Two reports of patients with the G551D mutation who had taken pancreatic enzyme replacement therapy (PERT) since infancy due to both symptoms and lab testing (spot fecal fat and fecal elastase) took ivacaftor and subsequently developed pancreatitis. Both were subsequently shown to have pancreatic sufficiency based on fecal elastase testing 7,8 . Another child, while taking ivacaftor, discontinued PERT except with very fatty meals based on lack of symptoms of pancreatic insufficiency.…”