CFTR modulators increase risk of acute pancreatitis in pancreatic insufficient patients with cystic fibrosis

Gould, Michelle; Smith, Haley; Rayment, Jonathan H.; Machida, H; Gonska, Tanja; Galante, Gary

doi:10.1016/j.jcf.2021.09.010

Cited by 31 publications

(29 citation statements)

References 7 publications

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“…Patients with pancreas-sufficient cystic fibrosis are at risk of acute pancreatitis, a risk that can be reduced by CFTR modulator therapy as with ivacaftor and/or tezacaftor [233], although CFTR modulator therapy with ivacaftor or lumacaftor-ivacaftor that restores exocrine function in pancreas-insufficient cystic fibrosis may increase the risk of acute pancreatitis [234]. In patients with disabling recurrent idiopathic pancreatitis with or without associated mutations, for example in CFTR or SPINK-1, consideration should be given to more invasive measures, although surgery is unlikely to be appropriate unless there is clear morphological evidence of chronic pancreatitis.…”

Section: Prevention Of Recurrencementioning

confidence: 99%

Acute Pancreatitis: Diagnosis and Treatment

Szatmary

Grammatikopoulos

Cai

et al. 2022

Drugs

249

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Acute pancreatitis is a common indication for hospital admission, increasing in incidence, including in children, pregnancy and the elderly. Moderately severe acute pancreatitis with fluid and/or necrotic collections causes substantial morbidity, and severe disease with persistent organ failure causes significant mortality. The diagnosis requires two of upper abdominal pain, amylase/lipase ≥ 3 ×upper limit of normal, and/or cross-sectional imaging findings. Gallstones and ethanol predominate while hypertriglyceridaemia and drugs are notable among many causes. Serum triglycerides, full blood count, renal and liver function tests, glucose, calcium, transabdominal ultrasound, and chest imaging are indicated, with abdominal crosssectional imaging if there is diagnostic uncertainty. Subsequent imaging is undertaken to detect complications, for example, if C-reactive protein exceeds 150 mg/L, or rarer aetiologies. Pancreatic intracellular calcium overload, mitochondrial impairment, and inflammatory responses are critical in pathogenesis, targeted in current treatment trials, which are crucially important as there is no internationally licenced drug to treat acute pancreatitis and prevent complications. Initial priorities are intravenous fluid resuscitation, analgesia, and enteral nutrition, and when necessary, critical care and organ support, parenteral nutrition, antibiotics, pancreatic exocrine and endocrine replacement therapy; all may have adverse effects. Patients with local complications should be referred to specialist tertiary centres to guide further management, which may include drainage and/or necrosectomy. The impact of acute pancreatitis can be devastating, so prevention or reduction of the risk of recurrence and progression to chronic pancreatitis with an increased risk of pancreas cancer requires proactive management that should be long term for some patients.

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Section: Prevention Of Recurrencementioning

confidence: 99%

Acute Pancreatitis: Diagnosis and Treatment

Szatmary

Grammatikopoulos

Cai

et al. 2022

Drugs

249

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“…This was highlighted by a case report describing normal pancreatic function and false negative CF newborn screen in a child born to a mother taking ETI therapy during pregnancy [27]. Insufficient residual acinar reserve associated with pancreatic insufficiency (PI) makes the development of pancreatitis very unusual in PI CF [28,29]. However, CFTR modulators have been linked to a small increase risk of acute pancreatitis in this patient group, supporting a possible increase in acinar cell function [29].…”

Section: Exocrine Pancreasmentioning

confidence: 97%

Nutritional and metabolic management for cystic fibrosis in a post-cystic fibrosis transmembrane conductance modulator era

Wilschanski

Peckham

2022

Current Opinion in Pulmonary Medicine

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Purpose of reviewThe introduction of highly effective cystic fibrosis transmembrane conductance regulator modulators has resulted in a paradigm shift towards treating underlying cause of cystic fibrosis (CF) rather than the ensuing complications. In this review, we will describe the impact of these small molecules on growth, nutrition, and metabolic status in people with CF (pwCF). Recent findingResults of clinical trials and real world data demonstrate that these small molecules are having a significant impact of on augmenting body weight, improving nutritional status and reducing gastrointestinal symptom burden. Early treatment can also positively impact on pancreatic endocrine and exocrine function.

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“…The clinical outcome of pancreatitis has also been associated with modulator use. A case series of 5 PwCF with pancreatic insufficiency, demonstrated increased risk of acute pancreatitis after use of modulator (IVA or LUM/IVA) 17 . In contrast, using MarketScan, a database of inpatient and outpatient health care covering over 200 million individuals, an overall reduction in acute pancreatitis in both pancreatic sufficient and insufficient patients was seen after introduction of CFTR modulators 18 .…”

Section: Lumacaftor/ivacaftormentioning

confidence: 99%

Cystic fibrosis year in review 2021

Savant

2022

Preprint

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People with cystic fibrosis (CF) have an amazing outlook with the treatment availability of highly effective modulators. Unfortunately, not all PwCF are eligible for modulators leading to continued pulmonary exacerbations and advanced lung disease. Additionally, optimizing diagnosis and evaluation for CF in the newborn period continues to be an area of focus for research. This review article will work to cover articles published in 2021 with high clinical relevance related to the above topics, however due to the extensive body of research published, this review will not be comprehensive.

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CFTR modulators increase risk of acute pancreatitis in pancreatic insufficient patients with cystic fibrosis

Cited by 31 publications

References 7 publications

Acute Pancreatitis: Diagnosis and Treatment

Acute Pancreatitis: Diagnosis and Treatment

Nutritional and metabolic management for cystic fibrosis in a post-cystic fibrosis transmembrane conductance modulator era

Cystic fibrosis year in review 2021

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