Citrulline correlations in short bowel syndrome-intestinal failure by patient stratification: Analysis of 24 weeks of teduglutide treatment from a randomized controlled study

Abstract

Background & aims: Disease-associated factors influence parenteral support (PS) reduction in response to teduglutide in patients with intestinal failure associated-short bowel syndrome (SBS-IF). We sought to determine correlative relationships between plasma citrulline levels, small bowel length, and PS volume.

Methods: A post hoc analysis of plasma citrulline levels from patients in the STEPS 24-week study of teduglutide in patients with SBS-IF. Plasma citrulline was assessed in all patients; patients were stratified 3 times into subgroups based on bowel anatomy, cause of SBS-IF, and baseline PS volumes. Correlation analyses used simple linear regression models. Statistical comparisons between study groups were conducted using 2-sided t tests for 2 independent mean differences.

Results: Baseline plasma citrulline correlated with remnant small bowel length (r = 0.355, P = 0.002), but not with baseline PS volume (r = -0.167, P = 0.14), in the overall population. There was a robust correlation between the baseline and Week 24 citrulline (r = 0.705, P < 0.0001), and an inverse correlation between change from baseline in citrulline and PS volume from baseline to Week 24 (r = -0.359, P = 0.001). In all subgroups, patients treated with teduglutide showed numerically greater increases in plasma citrulline at Week 24 compared with placebo.

Conclusion: Baseline plasma citrulline showed significant correlations with small bowel length in patients with ≥50% colon remaining/no stoma/colon-in-continuity, and patients with SBS-IF causes other than IBD/vascular disease. Citrulline levels may correlate with PS changes in response to teduglutide and more research may reveal a relationship between citrulline levels within the heterogeneous population of patients with SBS-IF. ClinicalTrials.gov NCT00798967, ClinicalTrialsRegister.eu 2008-006193-15.

Keywords: Citrulline; Intestinal failure; Parenteral support; Short bowel syndrome; Teduglutide.

Conflict of interest statement

Conflict of interest Shire is a member of the Takeda group of companies; NPS Pharmaceuticals, Inc., is a wholly owned indirect subsidiary of Shire. PBJ has served as a speakers bureau member and consultant for Shire, and as a study investigator, consultant, and advisory board member for NPS Pharmaceuticals, Inc. SMG has served as an advisory board member and consultant for Shire, and as an advisory board member and study investigator for NPS Pharmaceuticals, Inc. DLS has served as an advisory board member and consultant for Shire, and as an advisory board member and study investigator for NPS Pharmaceuticals, Inc. H-ML and CO are employees of Shire, a member of the Takeda group of companies.

Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.