Pancreatic Enzyme Replacement Therapy Use in Infants With Cystic Fibrosis Diagnosed by Newborn Screening

Abstract

Objectives: The aim of the study is to describe pancreatic enzyme practices during the first year of life in infants with cystic fibrosis (CF) and evaluate associations between dosing and outcomes, including growth and gastrointestinal (GI) symptoms.

Methods: We analyzed data from a subset of infants who were in a prospective cohort study conducted at 28 US CF centers. Anthropometric measurements and medications were recorded at each visit. Diaries with infant diet, pancreatic enzyme replacement therapy (PERT) dosing, stool frequency and consistency, and pain were completed by a parent/guardian for 3 days before each visit.

Results: Two hundred and thirty-one infants were enrolled in the main study; 205 of these met criteria for pancreatic insufficiency (PI). PERT dose between birth and 6 months was on average 1882 LU/kg per meal (range: 492-3727) and was similar between 6 and 12 months (mean: 1842 LU/kg per mean, range: 313-3612). PERT dose had a weak, negative association with weight z score at 3 and 6 months (r = -0.16, 95% confidence interval [CI] -0.29 to -0.02 and r = -0.18, 95% CI -0.31 to -0.04, respectively) but not at 12 months. There was not a clear relationship between PERT dosing and number of stools per day, stool consistency or pain. One hundred and forty-four infants (70%) were placed on acid suppression medication. Weight z score mean was 0.37 higher in infants using proton pump inhibitors (PPIs) exclusively versus those using histamine-2 blockers exclusively (95% CI -0.02 to 0.76, P = 0.06).

Conclusions: We did not observe that centers with a higher PERT dosing strategy yielded greater clinical benefit than dosing at the lower end of the recommended range.

Trial registration: ClinicalTrials.gov NCT01424696.

Conflict of interest statement

Conflict of interest disclosures and Sources of Funding: Dr Gelfond has served as a consultant for Vertex, Abbvie and Chiesi Pharmaceuticals. Dr. Leung has served as a consultant for Vertex and receives research/grant support from Bristol Meyers Squibb, Gilead, Abbvie, and Roche pharmaceuticals outside of the submitted work. Dr. Ramsey discloses that over the past 3 years she has received grant support from the Cystic Fibrosis Foundation and the National Institutes of Health. She has been the principal investigator on contracts between Seattle Children’s Hospital and the following companies: Aridis Pharmaceuticals, LLC, Celtaxsys, Kalobios, Flatley Discovery Labs, LLV, Vertex Pharmaceuticals Inc, Laurent Therapeutics, Inc, Nilvalis Therapeutics, Inc, and Synedgen, Inc. Dr Heubi has received personal fees from Alynlam Pharma and has financial interest in Asklepion Pharma LLC. No other disclosures are reported.

Figures

Figure 1

Weight for age z-score by PERT dose at (a) 3, (b) 6, and (c) 12 months.

Figure 2

Participant median dose (over entire year) and mean 12 month weight for age z-score by Site. White squares= higher dosing sites’ participants; black circles=lower dosing sites’ participants; gray triangles=mid-range dosing sites’ participants

Figure 3

Average weight and length for age over the first year of life by site PERT dosing. Gray solid line= lower PERT dosing sites; black hashed line= higher PERT dosing sites; p-value is for overall test of difference between curves.