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Early use of teduglutide in paediatric patients with intestinal failure is associated with a greater response rate: a multicenter study

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Abstract

Teduglutide is a glucagon-like-peptide-2 analogue that reduces the need for parenteral support in patients with short bowel syndrome (SBS). Nevertheless, data about long-term therapy with teduglutide in children are still scarce. Our objective was to describe the real-life experience with teduglutide in children with SBS over the last 5 years in Spain. This was a national multicentre and prospective study of paediatric patients with intestinal failure (IF) treated with teduglutide for at least 3 months. The data included demographic characteristics, medical background, anthropometric data, laboratory assessments, adverse events, and parenteral nutrition (PN) requirements. Treatment response was defined as a > 20% reduction in the PN requirement. The data were collected from the Research Electronic Data Capture (REDCap) database. Thirty-one patients from seven centres were included; the median age at the beginning of the treatment was 2.3 (interquartile range (IQR) 1.4–4.4) years; and 65% of the patients were males. The most frequent cause of IF was SBS (94%). The most common cause of SBS was necrotizing enterocolitis (35%). The median residual bowel length was 29 (IQR 12–40) cm. The median duration of teduglutide therapy was 19 (IQR 12–36) months, with 23 patients (74%) treated for > 1 year and 9 treated for > 3 years. The response to treatment was analysed in 30 patients. Twenty-four patients (80%) had a reduction in their weekly PN energy > 20% and 23 patients (77%) had a reduction in their weekly PN volume > 20%. Among the responders, 9 patients (29%) were weaned off PN, with a median treatment duration of 6 (IQR 4.5–22) months. The only statistically significant finding demonstrated an association between a > 20% reduction in the weekly PN volume and a younger age at the start of treatment (p = 0.028).

   Conclusions: Teduglutide seems to be an effective and safe treatment for paediatric patients with IF. Some patients require a prolonged duration of treatment to achieve enteral autonomy. Starting treatment with teduglutide at a young age is associated with a higher response rate.

What is Known:

•  Glucagon-like peptide-2 (GLP-2) plays a crucial role in the regulation of intestinal adaptation in short bowel syndrome (SBS). Teduglutide is a GLP-2 analog that reduces the need for parenteral support in patients with SBS.

• Data about long-term therapy with teduglutide in children in real life are still scarce.

What is New:

• Most pediatric patients with SBS respond in a satisfactory manner to teduglutide treatment. The occurrence of long-term adverse effects is exceptional.

• Starting treatment with the drug at a young age is associated with a greater response rate.

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Data availability

No datasets were generated or analysed during the current study.

Abbreviations

BMI:

Body mass index

GLP-2:

Glucagon-like peptide-2

HPN:

Home parenteral nutrition

IF:

Intestinal failure

PN:

Parenteral nutrition

SBS:

Short bowel syndrome

References

  1. Norsa L, Goulet O, Alberti D, DeKooning B, Domellöf M, Haiden N, Hill S, Indrio F, Kӧglmeier J, Lapillonne A et al (2023) Nutrition and intestinal rehabilitation of children with short bowel syndrome: a position paper of the ESPGHAN Committee on Nutrition. Part 1: from intestinal resection to home discharge. J Pediatr Gastroenterol Nutr 77(2):281–297

    Article  PubMed  Google Scholar 

  2. Duggan CP, Jaksic T (2017) Pediatric intestinal failure. N Engl J Med 377(7):666–675

    Article  CAS  PubMed  Google Scholar 

  3. Andrés Moreno AM, Ramos Boluda E, Hernández OF (2023) Pediatric intestinal failure: an update. Cir Pediatr 36(3):97–109

    PubMed  Google Scholar 

  4. Pironi L, Arends J, Baxter J, Bozzetti F, Peláez RB, Cuerda C, Forbes A, Gabe S, Gillanders L, Holst M et al (2015) Home artificial nutrition & chronic intestinal failure; acute intestinal failure special interest groups of ESPEN. ESPEN endorsed recommendations. Definition and classification of intestinal failure in adults. Clin Nutr 34(2):171–180

    Article  PubMed  Google Scholar 

  5. Goulet O, Ruemmele F (2006) Causes and management of intestinal failure in children. Gastroenterology 130(2 Suppl 1):S16-28

    Article  CAS  PubMed  Google Scholar 

  6. Tappenden KA (2014) Intestinal adaptation following resection. JPEN J Parenter Enteral Nutr 38(1 Suppl):23S-31S

    PubMed  Google Scholar 

  7. Sigalet DL (2018) Advances in glucagon like peptide-2 therapy. physiology, current indications and future directions. Semin Pediatr Surg 27(4):237–241

    Article  CAS  PubMed  Google Scholar 

  8. Tee CT, Wallis K, Gabe SM (2011) Emerging treatment options for short bowel syndrome: potential role of teduglutide. Clin Exp Gastroenterol 4:189–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Drucker DJ, Erlich P, Asa SL, Brubaker PL (1996) Induction of intestinal epithelial proliferation by glucagon-like peptide 2. Proc Natl Acad Sci U S A 93(15):7911–7916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Thulesen J (2004) Glucagon-like peptide 2 (GLP-2), an intestinotrophic mediator. Curr Protein Pept Sci 5(1):51–65. https://doi.org/10.2174/1389203043486946. PMID: 14965320

    Article  CAS  PubMed  Google Scholar 

  11. Pironi L, Allard JP, Joly F, Geransar P, Genestin E, Pape UF. Use of teduglutide in adults with short bowel syndrome-associated intestinal failure. Nutr Clin Pract. 2024 Feb;39(1):141-153.

  12. Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O’Keefe SJ (2011) Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut 60(7):902–914

    Article  CAS  PubMed  Google Scholar 

  13. O’Keefe SJ, Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B (2013) Safety and efficacy of teduglutide after 52 weeks of treatment in patients with short bowel intestinal failure. Clin Gastroenterol Hepatol 11(7):815-823.e1–3

    Article  PubMed  Google Scholar 

  14. Carter BA, Cohran VC, Cole CR, Corkins MR, Dimmitt RA, Duggan C, Hill S, Horslen S, Lim JD, Mercer DF et al (2017) Outcomes from a 12-week, open-label, multicenter clinical trial of teduglutide in pediatric short bowel syndrome. J Pediatr 181:102-111.e5

    Article  CAS  PubMed  Google Scholar 

  15. Kocoshis SA, Merritt RJ, Hill S, Protheroe S, Carter BA, Horslen S, Hu S, Kaufman SS, Mercer DF, Pakarinen MP, Venick RS et al (2020) Safety and efficacy of teduglutide in pediatric patients with intestinal failure due to short bowel syndrome: a 24-week, phase III study. JPEN J Parenter Enteral Nutr 44(4):621–631

    Article  CAS  PubMed  Google Scholar 

  16. Lambe C, Talbotec C, Kapel N, Barbot-Trystram L, Brabant S, Nader EA, Pigneur B, Payen E, Goulet O (2023) Long-term treatment with teduglutide: a 48-week open-label single-center clinical trial in children with short bowel syndrome. Am J Clin Nutr 117(6):1152–1163

    Article  CAS  PubMed  Google Scholar 

  17. Gigola F, Cianci MC, Cirocchi R, Ranucci MC, Del Riccio M, Coletta R, Morabito A (2022) Use of teduglutide in children with intestinal failure: a systematic review. Front Nutr 14(9):866518

    Article  Google Scholar 

  18. Chiba M, Masumoto K, Kaji T, Matsuura T, Morii M, Fagbemi A, Hill S, Pakarinen MP, Protheroe S, Urs A et al (2023) Efficacy and safety of teduglutide in infants and children with short bowel syndrome dependent on parenteral support. J Pediatr Gastroenterol Nutr 77(3):339–346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ramos Boluda E, Redecillas Ferreiro S, Manrique Moral O, García Romero R, Irastorza Terradillos I, Nuñez Ramos R, Germán Díaz M, Polo Miquel B, Vives Piñera I, Alcolea Sánchez A et al (2020) Experience with teduglutide in pediatric short bowel syndrome: first real-life data. J Pediatr Gastroenterol Nutr 71(6):734–739

    Article  PubMed  Google Scholar 

  20. Guz-Mark A, Hino B, Berkowitz D, Hartman C, Millman PN, Orlanski-Meyer E, Shaoul R, Spector-Cohen I, Weiss B, Zangen T, Shamir R (2022) The variable response to teduglutide in pediatric short bowel syndrome: a single country real-life experience. J Pediatr Gastroenterol Nutr 75(3):293–298

    Article  CAS  PubMed  Google Scholar 

  21. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG (2009) Research electronic data capture (REDCap) – a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 42(2):377–381

    Article  PubMed  Google Scholar 

  22. Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O’Neal L, McLeod L, Delacqua G, Delacqua F, Kirby J, Duda SN, REDCap Consortium (2019) The REDCap consortium: building an international community of software platform partners. J Biomed Inform 95:103208

    Article  PubMed  PubMed Central  Google Scholar 

  23. Crenn P, Messing B, Cynober L (2008) Citrulline as a biomarker of intestinal failure due to enterocyte mass reduction. Clin Nutr 27(3):328–339

    Article  CAS  PubMed  Google Scholar 

  24. Norsa L, Goulet O, Alberti D, DeKooning B, Domellöf M, Haiden N, Hill S, Indrio F, Kӧglmeier J, Lapillonne A et al (2023) Nutrition and intestinal rehabilitation of children with short bowel syndrome: a position paper of the ESPGHAN Committee on Nutrition. Part 2: long-term follow-up on home parenteral nutrition. J Pediatr Gastroenterol Nutr 77(2):298–314

    Article  PubMed  Google Scholar 

  25. De Dreuille B, Nuzzo A, Bataille J, Mailhat C, Billiauws L, Le Gall M, Joly F (2023) Post-marketing use of teduglutide in a large cohort of adults with short bowel syndrome-associated chronic intestinal failure: evolution and outcomes. Nutrients 15(11):2448

    Article  PubMed  PubMed Central  Google Scholar 

  26. Fragkos KC, Forbes A (2018) Citrulline as a marker of intestinal function and absorption in clinical settings: a systematic review and meta-analysis. United European Gastroenterol J 6(2):181–191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We gratefully thank all parents and children enrolled in this study for their participation and trust.

Author information

Authors and Affiliations

  1. Pediatric Gastroenterology, Hepatology and Nutrition Department, Hospital Universitario, 12 de Octubre, Madrid, Spain

    Marta Germán-Díaz

  2. Intestinal Rehabilitation Unit, Hospital La Paz, Madrid, Spain

    Alida Alcolea, Rocío González-Sacristán & Esther Ramos-Boluda

  3. Pediatric Gastroenterology and Nutrition Support Unit, Hospital Vall D’Hebrón, Barcelona, Spain

    Vanessa Cabello & Susana Redecillas-Ferreiro

  4. Pediatric Gastroenterology and Nutrition Department, Hospital Regional Universitario de Málaga, Málaga, Spain

    Javier Blasco-Alonso

  5. Pediatric Gastroenterology Department, Hospital Universitario Virgen del Rocío, Seville, Spain

    Alejandro Rodríguez

  6. Pediatric Gastroenterology and Nutrition Department, Hospital Universitario Torrecárdenas, Almería, Spain

    Rafael Galera

  7. Pediatric Gastroenterology and Nutrition Department, Hospital Universitario Miguel Servet, Zaragoza, Spain

    Ruth García-Romero

  8. Research Institute, Hospital Universitario, 12 de Octubre, Madrid, Spain

    Carmen Romero

  9. Pediatric Department, Clínica Universitaria de Navarra, Madrid, Spain

    José Manuel Moreno-Villares

Authors
  1. Marta Germán-Díaz
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  2. Alida Alcolea
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  3. Vanessa Cabello
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  4. Javier Blasco-Alonso
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  5. Alejandro Rodríguez
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  6. Rafael Galera
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  7. Ruth García-Romero
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  8. Carmen Romero
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  9. Rocío González-Sacristán
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  10. Susana Redecillas-Ferreiro
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  11. José Manuel Moreno-Villares
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  12. Esther Ramos-Boluda
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Contributions

All authors contributed to the study conception and design. Material preparation was performed by Marta German-Diaz. The data were collected by Marta German-Diaz, Alida Alcolea, Vanessa Cabello, Javier Blasco-Alonso, Alejandro Rodríguez, Rafael Galera, Ruth García-Romero, and Rocío González-Sacristán. Analysis was performed by Marta German-Diaz and Carmen Romero. The first draft of the manuscript was written by Marta German-Diaz and all the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Marta Germán-Díaz.

Ethics declarations

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of Hospital Universitario 12 de Octubre (protocol code 19/542, date: 11/02/2020).

Consent to participate

Informed consent was obtained from all subjects involved in the study.

Competing interests

M.G-D., J.B-A., A.R., S.R., JM. M-V., and E.R-B. have served on advisory boards for Takeda. J.B-A., A.R., S.R., JM. M-V., and E.R-B have received speaker honorarium from Takeda. They did not receive honoraria in direct relation to this study. A.L., V.C., R.G., R.G-R., R.G-S., and C.R. have no financial interest.

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Communicated by Gregorio Milani

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Germán-Díaz, M., Alcolea, A., Cabello, V. et al. Early use of teduglutide in paediatric patients with intestinal failure is associated with a greater response rate: a multicenter study. Eur J Pediatr (2024). https://doi.org/10.1007/s00431-024-05577-5

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  • DOI: https://doi.org/10.1007/s00431-024-05577-5

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