Long-term Safety and Efficacy of Teduglutide for the Treatment of Intestinal Failure Associated with Short Bowel Syndrome: Final Results of the STEPS-2 Study, a 2-year, Multicenter, Open-label Clinical Trial

Abstract

Purpose: Treatment with teduglutide (TED) promotes intestinal adaptation and absorptive capacity in patients (pts) with intestinal failure associated with short bowel syndrome (SBS-IF). In a 24-wk placebo (PBO)-controlled phase III study (STEPS), TED significantly reduced parenteral nutrition and/or intravenous fluid (PN/IV) volume requirements and number of infusion days in pts with SBS-IF. The primary objective of STEPS-2 was to further assess long-term safety and efficacy of TED in pts with SBS-IF. Methods: This extension study enrolled pts who completed 24 wks of treatment with TED (TED/TED) or PBO (PBO/TED) in STEPS or qualified for STEPS but were not treated because target enrollment numbers were met (NT/TED). For safety analysis, PBO/TED and NT/TED groups were combined (PBO+NT/TED). All pts who completed the study received subcutaneous TED (0.05 mg/kg/d) for ≥24 mo; pts in the TED/TED group received TED for 30 mo. Clinical response was defined as a 20%-100% reduction from baseline in weekly PN/IV volume. Results: Of 88 adults enrolled (TED/TED, n=37; PBO/TED, n=39; NT/TED, n=12), 65 (74%) pts completed the study. At 24 mo, clinical response was achieved by 28/30 (93%) TED/TED pts, 16/29 (55%) PBO/TED pts, and 4/6 (67%) NT/TED pts. Mean PN/IV volume reduction from baseline was 7.6 (66%) L/wk, 3.1 (28%) L/wk, and 4.0 (39%) L/wk in the TED/TED, PBO/TED, and NT/TED groups, respectively. Overall, TED treatment resulted in additional days off PN/IV, with 25/65 (38%) pts achieving ≥3-d/wk reduction (TED/TED, 18/30 [60%] pts; PBO/TED, 5/29 [17%]; NT/TED, 2/6 [33%]). 13/88 (15%) pts, including 10 in the TED/TED group, achieved independence from PN/IV. These pts achieved independence from PN/IV after 24-114 wks of TED treatment. Treatment-emergent adverse events occurred in 84/88 (95%) pts; the most common were abdominal pain (34%), catheter sepsis (28%), and episodes of decreased weight (25%). Twenty-three pts discontinued treatment [16/51 (31%) in PBO+NT/TED and 7/37 (19%) in TED/TED groups]. 64% of pts experienced serious AEs. Conclusion: Long-term treatment with TED resulted in additional, clinically meaningful reductions in PN/IV support. Complete independence from PN/IV support was achieved by a heterogeneous group of pts with SBS-IF who received TED. No unexpected safety signals were detected. These data suggest that long-term TED treatment is associated with continued reductions in PN/IV support, and independence from PN/IV for some pts. This research was funded by NPS Pharmaceuticals, Inc., Bedminster, NJ. Disclosure - Lauren K. Schwartz is a consultant for NPS Pharmaceuticals, Inc. Stephen J. D. O'Keefe is a consultant and has received grant/research support from NPS Pharmaceuticals, Inc. Palle B. Jeppesen has received grant/research support and has been an advisory board member as well as other (site investigator on clinical trials) for NPS Pharmaceuticals, Inc. Marek Pertkiewicz is a consultant as well as other (site investigator on clinical trials) for NPS Pharmaceuticals, Inc. Nader N. Youssef is an employee of NPS Pharmaceuticals, Inc. Ken Fujioka is a consultant for NPS Pharmaceuticals, Inc.