Pancreatic insufficiency converted to pancreatic sufficiency with ivacaftor

Hamilton, Jennifer; Zobell, Jeffery T.; Robson, Jacob

doi:10.1002/ppul.24454

Cited by 18 publications

(12 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A case report has been published discussing two children with CF complicated by EPI who converted to pancreatic sufficiency after ivacaftor initiation. In both patients, an episode of acute pancreatitis prompted repeat fecal elastase testing which indicated recovery of exocrine pancreatic function 8 . While pancreatitis is an overall rare complication for patients with CF and typically associated with patients with pancreatic sufficiency, it may also be seen with CF patients with EPI.…”

Section: Discussionmentioning

confidence: 98%

“…The observed weight gain with increased fecal elastase values suggests the restoration of exocrine pancreatic function with ivacaftor 5,6 . More recently, specific case reports have been published describing cases of patients with CF previously diagnosed with EPI, who had clinical restoration of pancreatic function after initiation of ivacaftor 7,8 . These data suggest that exocrine pancreatic function may be modifiable with highly effective CFTR modulator therapy, in contrast to previously accepted models of pancreatic dysfunction in CF.…”

Section: Introductionmentioning

confidence: 88%

See 1 more Smart Citation

Persistent recovery of pancreatic function in patients with cystic fibrosis after ivacaftor

Munce

Lim

Akong

2020

Pediatric Pulmonology

View full text Add to dashboard Cite

Exocrine pancreatic insufficiency (EPI), which leads to malabsorption and poor weight gain, is seen in 85% of patients with cystic fibrosis (CF). EPI is treated with pancreatic enzyme replacement therapy taken with each meal. The highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator, ivacaftor, restores CFTR function in patients with responsive mutations. It is a widely held view that EPI in CF is irreversible due to the complete destruction of pancreatic ducts and acinar cells. We describe three pediatric CF patients with EPI who were started on ivacaftor, and subsequently showed evidence of restored exocrine pancreatic function with clinical and biochemical parameters.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 88%

Persistent recovery of pancreatic function in patients with cystic fibrosis after ivacaftor

Munce

Lim

Akong

2020

Pediatric Pulmonology

View full text Add to dashboard Cite

show abstract

“…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.…”

Section: Reversing the Irreversible: Another Potential Benefit Of Cftmentioning

confidence: 73%

Reversing the irreversible: Another potential benefit of CFTR modulators

Wright

Cannon

Ramsey

2020

Pediatric Pulmonology

View full text Add to dashboard Cite

“…Another major impact of early life introduction of modulators has been observed in trials in preschool children, namely the restoration of pancreatic exocrine function. Surprisingly, substantial increases in faecal elastase were seen in a proportion of 3 to 5 years old receiving ivacaftor 34 ; these have been observed in younger cohorts also, 35 and anecdotal reports in even older children are appearing in the literature 36,37 …”

Section: Great Progress: What Else Is Needed?mentioning

confidence: 97%

Entering the era of highly effective modulator therapies

Dave¹,

Dobra

Scott

et al. 2021

Pediatric Pulmonology

View full text Add to dashboard Cite

Since the discovery of the gene responsible for cystic fibrosis (CF) in 1989, hopes have been pinned on a future with novel therapies tackling the basis of the disease rather than its symptoms. These have become a reality over the last decade with the development through to the clinic of CF transmembrane conductance regulator (CFTR) modulators. These are oral drugs which improve CFTR protein function through either increasing the time the channel pore is open (potentiators) or facilitating its trafficking through the cell to its location on the cell membrane (correctors). The first potentiator, ivacaftor, is now licensed and available clinically in many parts of the world. It is highly effective with impressive clinical impact in the lungs and gastrointestinal tract; longer‐term data from patient registries show fewer exacerbations, a slower rate of lung function loss and reduced need for transplantation in patients receiving ivacaftor. However, as a single drug, it is suitable for only a small minority of patients. The commonest CFTR mutation, F508del, requires both correction and potentiation for clinical efficacy. Two dual‐agent drugs (lumacaftor/ivacaftor and tezacaftor/ivacaftor) have progressed through to licensing, although their short term impact is more modest than that of ivacaftor; this is likely due to only partial correction of protein misfolding and trafficking. Most recently, triple compounds have been developed: two different corrector molecules (elexacaftor and tezacaftor) which, by addressing different regions in the misfolded F508del protein, more effectively improve trafficking. In addition to large improvements in clinical outcomes in people with two copies of F508del, the combination is sufficiently effective that it works in patients with only one copy of F508del and a second, nonmodulator responsive mutation. For the first time, we thus have a drug suitable for around 85% of people with CF. Even more gains are likely to be possible when these drugs can be used in younger children, although more sensitive outcome measures are needed for this age group. Special consideration is needed for people with very rare mutations; those with nonmodulatable mutation combinations will likely require gene or messenger RNA‐based therapeutic approaches, many of which are being explored. Although this progress is hugely to be celebrated, we still have more work to do. The international collaboration between trials networks, pharma, patient organizations, registries, and people with CF is something we are all rightly proud of, but innovative trial design and implementation will be needed if we are to continue to build on this progress and further develop drugs for people with CF.

show abstract

Pancreatic insufficiency converted to pancreatic sufficiency with ivacaftor

Cited by 18 publications

References 3 publications

Persistent recovery of pancreatic function in patients with cystic fibrosis after ivacaftor

Persistent recovery of pancreatic function in patients with cystic fibrosis after ivacaftor

Reversing the irreversible: Another potential benefit of CFTR modulators

Entering the era of highly effective modulator therapies

Contact Info

Product

Resources

About