Gastrointestinal Burden in Patients with Pancreatic Insufficient Cystic Fibrosis Before and After Elexacaftor/Tezacaftor/Ivacaftor Use.

Background: The advent of highly effective modulator therapies (HEMT), namely elexacaftor, tezacaftor and ivacaftor (ETI), has resulted in substantial improvements in lung function, growth, and quality of life, for people with cystic fibrosis (PwCF). However, the understanding of the impact of ETI on gastrointestinal (GI) disease burden is evolving. This study aims to describe and compare the prevalence of GI manifestations, prescribed GI medications, and GI procedures between two time periods pre and post-ETI approval in children with CF (CwCF).

Methods: This is a retrospective cohort study utilizing TriNetX, a multicenter database. The study includes patients between 6 to 21 years old with ICD-10 diagnostic codes for CF and a prescription for pancreatic enzyme replacement therapy (PERT) to match disease severity. We included 4 years before and 4 years after the release of ETI combination therapy.

Results: When comparing CwCF taking PERT, on or off ETI, the prevalence of diagnostic codes for chronic pancreatitis, constipation, unspecified noninfective gastroenteritis, and colitis significantly decreased after ETI use (all P < 0.0001). The prevalence of other luminal disorders, liver disorders, and acute pancreatitis did not differ between the two groups. The prevalence of prescribed medications including mucolytics, vitamins, PPI, and antidiarrheal was similar for both groups except for a reduction in prescribed laxatives (p-value = 0.0001). The prevalence of GI procedures was also similar in both groups.

Conclusion: The reduction in constipation and non-infective gastroenteritis and colitis is important as GI symptoms are linked to the quality of life of CwCF. There remains a great clinical need to evaluate the effects of ETI on GI disorders, especially as the age of initial use of this therapy decreases, and the duration of use increases.