Predictors of Response to Teduglutide Among Patients with Parenteral Nutrition–Dependent Short Bowel Syndrome

Abstract

Introduction: The study aimed to identify factors associated with sustained parenteral nutrition (PN) volume reduction and early vs late responders among PN-dependent short bowel syndrome patients treated with teduglutide (TED). Methods: The study population was 43 patients receiving TED in a 24-week randomized placebo-controlled trial (STEPS: NCT00798967; EudraCT2008-006193-15) who could continue TED up to 24 months in the open-label extension (STEPS-2: NCT00930644; EudraCT2009-011679-65). Time to sustained PN volume reduction (i.e., PN volume reduction ≥20% at 2 consecutive visits) was calculated using Kaplan-Meier analysis. Multivariable Cox model was used to identify factors associated with sustained PN volume reduction. Among patients achieving sustained PN volume reduction, baseline characteristics were compared between early (PN volume reduction ≥20% at week 20 and 24) vs. late responders (sustained PN volume reduction at 2 consecutive visits after week 24). Results: The median time to sustained PN volume reduction was 4.2 months. Patients with stoma, compared to those without, were significantly more likely to achieve sustained PN volume reduction (hazard ratio [HR], 5.6; P = 0.01). Patients with an ileocecal valve, compared to those without (HR = 0.1; P = 0.03), and patients with major intestinal resection due to vascular disease, compared to those with Crohn’s disease (HR = 0.2; P = 0.02), were significantly less likely to achieve sustained PN volume reduction. Compared to late responders (n = 7), early responders (n = 27) were less likely to have colon-in-continuity (52% vs 100%; P = 0.02) and ileocecal valve (0% vs 29%; P < 0.01), and had smaller mean percentage of colon remaining (25% vs 57%; P = 0.02). The median time to sustained PN volume reduction was 3.7 months for early responders and 7.8 months for late responders. Conclusion: Presence of stoma and absence of ileocecal valve are good prognosis factors for achieving sustained PN volume reduction while vascular disease as cause of intestinal resection is a negative prognosis factor. Certain anatomical factors were significantly different between early and late responders. This research was funded by Shire Human Genetic Therapies, Inc., Lexington, MA, USA.