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P462 Impact of teduglutide, a GLP-2 agonist, on inflammatory bowel disease-associated short bowel syndrome: a tertiary single-center study

de Seze, M.(1);Billiauws, L.(1);Bettolo, J.(1);Damas, V.(1);Hutinet, C.(1);Bonvalet, F.(2);Cazals-Hatem, D.(3);Villain, C.(1);Bouhnik, Y.(1);Joly, F.(1);Uzzan, M.(4);

(1)Hopital Beaujon, Gastroenterology, Clichy, France;(2)Hopital Beaujon, Radiology, Clichy, France;(3)Hopital Beaujon, Pathology, Clichy, France;(4)Hôpital Beaujon- APHP, Gastroenterology- IBD unit, Paris, France

Background

Teduglutide (TED), a GLP2 agonist, have been shown to exert anti-inflammatory effects on the intestinal mucosa in murine preclinical models and evaluated with a positive trend in a phase 2a randomized controlled trial in non-short bowel syndrome (SBS) Crohn’s disease (CD) patients.
TED showed efficacy in reducing parenteral nutrition and or intravenous (PN/IV) dependence in SBS with intestinal failure (SBS-IF). However, limited data exists on its specific effect on the natural history of IBD in SBS patients treated with TED.
Therefore, we aimed to assess the efficacy and safety of TED in patients with IBD-associated SBS as well as the effect of TED on the course of IBD.

Methods

We conducted an observational retrospective study. Adult patients SBS-IF due to IBD and who were treated with TED were enrolled. Response was defined as a decrease of at least 20% in total volume of PN. Active IBD was defined based on morphologic and histologic data (CT-scan, colonoscopy and/or enteroMRI). Patients were followed until last news or TED discontinuation.

Results

We enrolled 14 IBD patients, including 2 patients with ulcerative colitis, with a median follow-up of 4.2 ± 4 years. Of the 12 CD patients, 11 had ileocolonic involvement and 1 had only small bowel involvement. 11 patients had type-1 SBS and 3 had type-2 SBS. 7 patients were only receiving intravenous fluid and 7 were on PN/IV. Patients were in average receiving PN/IV for 9.1 years at TED initiation.
Regarding IBD, 4 patients had active disease at inclusion, 3 with a structuring behavior and 1 with a fistulizing behavior. 5 patients were on biologic treatment (antiTNF or ustekinumab) at inclusion.
At month 3 (M3), 9 of 14 patients were responders. 3 were weaned from any iv supplementation. 3 of 7 patients initially on TPN were weaned from caloric input, including one still receiving iv fluids. Caloric input was in average at 7330 kcal/week at baseline versus 4615 at M3. Mean total parenteral volume went from 11849
ml/week at M0 to 8223 at M3.
2 of 4 patients with active disease at baseline showed improvement in disease activity while on TED. The latter 2 patients were totally weaned off PN/IV.Six patients withdrew TED during follow-up. 2 patients stopped after a diagnosis of cancer (1 melanoma and 1 chronic myeloid leukemia). Survival without TED discontinuation was estimated at 85.7 % IC95(69.2-100) at 1 year, 78.6% IC95(59.8-100) at 2 years and at 64.3% IC95(43.5-95) at 5 years

Conclusion

TED appears effective and safe in IBD-associated SBS-IF patients. In specific cases, it may impact positively the inflammatory course of the disease. Further prospective studies are warranted to specifically evaluate TED in IBD-associated SBS, including patients with active IBD.

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