Cystic Fibrosis Transmembrane Conductance Regulator Modulator Use Is Associated With Reduced Pancreatitis Hospitalizations in Patients With Cystic Fibrosis

Abstract

INTRODUCTION: Acute pancreatitis (AP) occurs among patients with pancreas-sufficient cystic fibrosis (PS-CF) but is reportedly less common among patients with pancreas-insufficient cystic fibrosis (PI-CF). The incidence of AP may be influenced by cystic fibrosis transmembrane conductance regulator (CFTR) modulator use. We hypothesized that CFTR modulators would reduce AP hospitalizations, with the greatest benefit in PS-CF. Methods: MarketScan (2012–2018) was queried for AP hospitalizations and CFTR modulator use among patients with CF. Multivariable Poisson models that enabled crossover between CFTR modulator treatment groups were used to analyze the rate of AP hospitalizations on and off therapy. Pancreas insufficiency was defined by the use of pancreas enzyme replacement therapy. Results: A total of 10,417 patients with CF were identified, including 1,795 who received a CFTR modulator. AP was more common in PS-CF than PI-CF (2.9% vs 0.9%, P = 0.007). Overall, the observed rate ratio of AP during CFTR modulator use was 0.33 (95% confidence interval [CI] 0.10, 1.11, P = 0.07) for PS-CF and 0.38 (95% CI 0.16, 0.89, P = 0.03) for PI-CF, indicating a 67% and 62% relative reduction in AP hospitalizations, respectively. In a subset analysis of 1,795 patients who all had some CFTR modulator use, the rate ratio of AP during CFTR modulator use was 0.36 (95% CI 0.13, 1.01, P = 0.05) for PS-CF and 0.53 (95% CI 0.18, 1.58, P = 0.26) for PI-CF. DISCUSSION: CFTR modulator use is associated with a reduction in AP hospitalizations among patients with CF. These observational data support the prospective study of CFTR modulators to reduce AP hospitalizations among patients with CF.

Cystic fibrosis year in review 2021

“…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 . Although these reports conflict, clinicians should be aware of possible pancreatitis in PwCF.…”

The Exocrine Pancreas in Cystic Fibrosis in the Era of CFTR Modulation: A Mini Review

“…Akshintala et al retrospectively reviewed a small cohort of adult CF patients with a history of pancreatitis in the preceding 2 years, highlighting that none of these 15 individuals developed pancreatitis during their follow up period (mean 36 months) (44). Ramsey and colleagues supported these findings 3 years onwards, demonstrating a significant reduction in pancreatitisrelated hospitalizations amongst those commenced on CFTR modulators amongst both PI and PS patients, with a greater relative risk reduction within the PS group (45). Overall, these findings suggest that in those suffering from recurrent pancreatitis, or who have a pre-existing risk of pancreatitis, CFTR modulators may assist in shifting away from this "risk window, " alleviating ductal obstruction enough to improve pancreatic output without inducing further inflammation.…”

Current and Future Therapeutic Approaches of Exocrine Pancreatic Insufficiency in Children with Cystic Fibrosis in the Era of Personalized Medicine

“…It suggests clinicians should be alert to pancreatitis symptoms in CF patients treated with these new therapies. Patients with recurrent pancreatitis (pancreatic sufficient patients) treated with CFTR modulators, may have a reduced risk of symptomatic pancreatitis [ 115 ].…”