O046
COLORECTAL CANCER INCIDENCE IN ADULTS WITH SHORT BOWEL SYNDROME AND INTESTINAL FAILURE EVER- OR NEVER-TREATED WITH TEDUGLUTIDE: INTERIM REGISTRY ANALYSIS VERSUS GENERAL POPULATION
P. B. JEPPESEN1,*, Y. W. Huang2, J. P. Allard3, G. E. Gondolesi4, F. Joly5, J. B. Mason6, S. Milicevic7, U.-F. Pape8,9, L. Pironi10, S. Ritter11, L. K. Schwartz12, I. Yunusa2, P. Zhang2, S. Sabrdaran2
1Rigshospitalet, Copenhagen, Denmark, 2Takeda Development Center Americas, Inc., Cambridge, United States, 3Toronto General Hospital, Toronto, Canada, 4Medstar Georgetown Transplant Institute, Washington, United States, 5Beaujon Hospital, Paris, France, 6Tufts Medical Center and Tufts University, Boston, United States, 7Takeda Pharmaceuticals International AG, Zurich, Switzerland, 8Asklepios Klinik St. Georg, Hamburg, 9Charité University Medicine Berlin, Berlin, Germany, 10University of Bologna, Bologna, Italy, 11Cytel Inc. [Contracted to Takeda Development Center Americas, Inc. at the time of the study], Cambridge, 12NYU Langone Health, New York, United States
Rationale: Teduglutide is a glucagon-like peptide-2 analogue indicated for short bowel syndrome and intestinal failure (SBS-IF). In animal models, teduglutide has shown potential to cause neoplastic changes. The SBS Registry (NCT01990040; EUPAS7973) is a global, real-world study of patients with SBS-IF. We compared colorectal cancer (CRC) incidence with expected rates if the same individuals were observed in the general population, using the TriNetX database (>51 million individuals) as a reference cohort.
Methods: Data from June 23, 2014–March 31, 2025 (interim cutoff) were analysed for adults ever- or never-treated with teduglutide with any remnant colon and no baseline CRC. CRC incidence rates (IRs) per 100 000 patient-years (PY) were calculated. Standardised morbidity ratios (SMRs) were estimated from SBS Registry data using TriNetX-adjusted reference rates by age group, gender, geographical region and inflammatory bowel disease status. Those with prior CRC were excluded. CRC risk was assessed to rule out a 3.1-fold increase using a 1-sided SMR 95% confidence interval (CI) <3.1.
Results: Among 457 ever-treated patients, 3 CRC events occurred in 2 patients over 2125.5 PY (IR: 94.1; Figure). After adjustment, the expected number of patients with an event was 6.02 (adjusted IR: 283.3), with an SMR of 0.332 (1-sided 95% upper CI: 1.04). Among 519 never-treated patients, 1 patient had a CRC event over 2070.1 PY (IR: 48.3). After adjustment, the expected number of patients with an event was 7.10 (adjusted IR: 343.1), with an SMR of 0.141 (1-sided 95% upper CI: 0.67). In both groups, upper CI limits remained below the 3.1 threshold.
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Conclusion: In adults with SBS-IF, CRC risk was not higher among patients ever- or never-treated with teduglutide than expected general population rates up to 10 years.
Disclosure of Interest: P. B. JEPPESEN Consultant for: Commercial relationships as consultant and speaker with Albumedix, ArTara Therapeutics, Baxter Healthcare, Coloplast, Ferring Pharmaceuticals, Fresenius Kabi, GLyPharma Therapeutic, Ironwood Pharmaceuticals, Naia Pharmaceuticals, NorthSea Therapeutics, Novo Nordisk Foundation, Protara Therapeutics, Takeda, Therachon, VectivBio/Ironwood and Zealand Pharma, Other: Compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study, Y. W. Huang Other: Employee of Takeda Development Center Americas, Inc. and has received stock and/or stock options, J. Allard Grant / Research Support from: Takeda as a study site principal investigator (PI); research support from OMS as a PI, Consultant for: Takeda, Speakers Bureau of: Takeda, Other: Compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study, G. Gondolesi Grant / Research Support from: Investigator-initiated research grant from Takeda, Speakers Bureau of: Takeda, Other: Compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study, F. Joly Consultant for: Advisory board member for Alira Health, ArTara Therapeutics, Baxter Healthcare, Ironwood Pharmaceuticals, M3E Solutions, NorthSea Therapeutics, Takeda, VectivBio and Zealand Pharma, Speakers Bureau of: Commercial relationships as a consultant and speaker for Auxens, Baxter Healthcare, B. Braun, Fresenius Kabi, Nestlé Health Sciences, Takeda and Théradial, Other: Compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; study investigator for NPS Pharmaceuticals, Takeda, VectivBio and Zealand Pharma, J. Mason Grant / Research Support from: Takeda as a site for the study, Other: Compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study; compensation from Care/of, a producer of nutritional supplements; fees from UpToDate, a web-based medical information platform, for authoring chapters, S. Milicevic Other: Employee of Takeda Pharmaceuticals International AG and has received stock and/or stock options, U.-F. Pape Grant / Research Support from: Hanmi, Takeda, VectivBio and Zealand Pharma as a study site PI., Consultant for: Takeda, Speakers Bureau of: Takeda, Other: Compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study, L. Pironi Grant / Research Support from: Personal grants for congress presentations from Baxter and B. Braun, Consultant for: Advisory board member for Alfasigma, NorthSea Therapeutics, and Takeda, Other: Compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study, S. Ritter Other: Employee of Cytel Inc. and funded by Takeda Development Center Americas, Inc. to perform statistical analyses for this study, L. Schwartz Grant / Research Support from: Research support received from Takeda as a study PI, Other: Compensation received from Takeda as a member of the Scientific Advisory Committee for the SBS Registry study, I. Yunusa Other: Employee of Takeda Development Center Americas, Inc. and has received stock and/or stock options, P. Zhang Other: Employee of Takeda Development Center Americas, Inc. and has received stock and/or stock options, S. Sabrdaran Other: Employee of Takeda Development Center Americas, Inc. and has received stock and/or stock options