Multicenter Study

. 2025 May 8;19(5):jjae182.

doi: 10.1093/ecco-jcc/jjae182.

Upadacitinib for Induction of Remission in Pediatric Ulcerative Colitis: An International Multicenter Study

Anat Yerushalmy-Feler^{1

2}, Elizabeth A Spencer³, Michael T Dolinger³, David L Suskind^{4

5}, Katarina Mitrova⁶, Ondrej Hradsky⁶, Máire A Conrad⁷, Judith R Kelsen⁷, Holm H Uhlig^{8

9

10

11}, Christos Tzivinikos¹², Silvana Ancona¹³, Magdalena Wlazlo¹⁴, Lukas Hackl¹⁵, Dror S Shouval^{16

17}, Matteo Bramuzzo¹⁸, Darja Urlep¹⁹, Christine Olbjorn²⁰, Giulia D'Arcangelo²¹, Gemma Pujol-Muncunill²², Dotan Yogev²³, Ben Kang²⁴, Marco Gasparetto²⁵, Christine Rungø²⁶, Kaija-Leena Kolho²⁷, Iva Hojsak²⁸, Lorenzo Norsa²⁹, Firas Rinawi³⁰, Naire Sansotta³¹, Ramit Magen Rimon³², Maya Granot^{17

33}, Luca Scarallo³⁴, Eunice Trindade³⁵, Marta Velasco Rodríguez-Belvís³⁶, Dan Turner²², Shlomi Cohen^{1

2}

Affiliations

¹ Pediatric Gastroenterology Institute, "Dana-Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
² Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
³ Division of Pediatric Gastroenterology, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁴ University of Washington Medical School, Seattle, WA, USA.
⁵ Seattle Children's Hospital IBD Center, Seattle, WA, USA.
⁶ Department of Paediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
⁷ Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA,USA.
⁸ Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
⁹ Biomedical Research Centre, University of Oxford, Oxford, UK.
¹⁰ Department of Paediatrics, University of Oxford, Oxford, UK.
¹¹ Centre of Human Genetics, University of Oxford, Oxford, UK.
¹² Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates.
¹³ Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Children and Young People, Edinburgh, Scotland.
¹⁴ Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland.
¹⁵ Department of Pediatrics I, Medical University Innsbruck, Innsbruck, Austria.
¹⁶ Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
¹⁷ Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
¹⁸ Institute for Maternal and Child Health-IRCCS "Burlo Garofolo," Trieste, Italy.
¹⁹ Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital Ljubljana, Ljubljana, Slovenia.
²⁰ Department of Paediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway.
²¹ Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza-University of Rome, Rome, Italy.
²² Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain.
²³ The Juliet Keidan Institute of Paediatric Gastroenterology and Nutrition, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
²⁴ Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea.
²⁵ Norfolk and Norwich University Hospital, Jenny Lind Children's Hospital, and University of East Anglia, Norwich Medical School, Norwich, UK.
²⁶ Department of Paediatric and Adolescence Medicine, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
²⁷ Department of Paediatric Gastroenterology, Children's Hospital, HUS and University of Helsinki, Helsinki, Finland.
²⁸ Children's Hospital Zagreb, University of Zagreb Medical School, Zagreb, Croatia.
²⁹ Pediatric Department, Children's Hospital Vittore Buzzi, University of Milan, Milan, Italy.
³⁰ Pediatric Gastroenterology Unit and Faculty of Medicine Technion, Haifa, Emek Medical Centre, Afula, Israel.
³¹ Pediatric Hepatology, Gastroenterology and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy.
³² Rambam Health Care Campus and the Faculty of Medicine, Pediatric Gastroenterology & Nutrition Institute, Ruth Rappaport Children's Hospital, Technion, Israel Institute of Technology, Haifa, Israel.
³³ Pediatric Gastroenterology Unit, Edmond & Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel.
³⁴ Gastroenterology and Nutrition Unit, Meyer Children's Hospital, Florence, Italy.
³⁵ Pediatric Gastroenterology and Nutrition Unit, Centro Hospitalar Universitário São João, Porto, Portugal.
³⁶ Department of Pediatric Gastroenterology and Nutrition, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.

PMID: 39605286
PMCID: PMC12548835
DOI: 10.1093/ecco-jcc/jjae182

Multicenter Study

Upadacitinib for Induction of Remission in Pediatric Ulcerative Colitis: An International Multicenter Study

Anat Yerushalmy-Feler et al. J Crohns Colitis. 2025.

. 2025 May 8;19(5):jjae182.

doi: 10.1093/ecco-jcc/jjae182.

Authors

Affiliations

¹ Pediatric Gastroenterology Institute, "Dana-Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
² Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
³ Division of Pediatric Gastroenterology, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁴ University of Washington Medical School, Seattle, WA, USA.
⁵ Seattle Children's Hospital IBD Center, Seattle, WA, USA.
⁶ Department of Paediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
⁷ Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA,USA.
⁸ Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
⁹ Biomedical Research Centre, University of Oxford, Oxford, UK.
¹⁰ Department of Paediatrics, University of Oxford, Oxford, UK.
¹¹ Centre of Human Genetics, University of Oxford, Oxford, UK.
¹² Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates.
¹³ Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Children and Young People, Edinburgh, Scotland.
¹⁴ Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland.
¹⁵ Department of Pediatrics I, Medical University Innsbruck, Innsbruck, Austria.
¹⁶ Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
¹⁷ Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
¹⁸ Institute for Maternal and Child Health-IRCCS "Burlo Garofolo," Trieste, Italy.
¹⁹ Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital Ljubljana, Ljubljana, Slovenia.
²⁰ Department of Paediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway.
²¹ Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza-University of Rome, Rome, Italy.
²² Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain.
²³ The Juliet Keidan Institute of Paediatric Gastroenterology and Nutrition, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
²⁴ Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea.
²⁵ Norfolk and Norwich University Hospital, Jenny Lind Children's Hospital, and University of East Anglia, Norwich Medical School, Norwich, UK.
²⁶ Department of Paediatric and Adolescence Medicine, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
²⁷ Department of Paediatric Gastroenterology, Children's Hospital, HUS and University of Helsinki, Helsinki, Finland.
²⁸ Children's Hospital Zagreb, University of Zagreb Medical School, Zagreb, Croatia.
²⁹ Pediatric Department, Children's Hospital Vittore Buzzi, University of Milan, Milan, Italy.
³⁰ Pediatric Gastroenterology Unit and Faculty of Medicine Technion, Haifa, Emek Medical Centre, Afula, Israel.
³¹ Pediatric Hepatology, Gastroenterology and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy.
³² Rambam Health Care Campus and the Faculty of Medicine, Pediatric Gastroenterology & Nutrition Institute, Ruth Rappaport Children's Hospital, Technion, Israel Institute of Technology, Haifa, Israel.
³³ Pediatric Gastroenterology Unit, Edmond & Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel.
³⁴ Gastroenterology and Nutrition Unit, Meyer Children's Hospital, Florence, Italy.
³⁵ Pediatric Gastroenterology and Nutrition Unit, Centro Hospitalar Universitário São João, Porto, Portugal.
³⁶ Department of Pediatric Gastroenterology and Nutrition, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.

PMID: 39605286
PMCID: PMC12548835
DOI: 10.1093/ecco-jcc/jjae182

Abstract

Background and aims: Data on upadacitinib therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBD-U) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric UC or IBD-U.

Methods: In this multicenter retrospective study, children treated with upadacitinib for induction of remission of active UC or IBD-U from 30 centers worldwide were enrolled. Demographic, clinical, and laboratory data, as well as adverse events (AEs), were recorded at Week 8 post-induction.

Results: One hundred children were included (90 UC and 10 IBD-U, median age 15.6 [interquartile range 13.3-17.1] years). Ninety-eight were previously treated with biologic therapies, and 76 were treated with ≥2 biologics. At the end of the 8-week induction period, clinical response, clinical remission, and corticosteroid-free clinical remission (CFR) were observed in 84%, 62%, and 56% of the children, respectively. Normal C-reactive protein and fecal calprotectin (FC) <150 mcg/g were achieved in 75% and 50%, respectively. Combined CFR and FC remission was observed in 18/46 (39%) children with available data at 8 weeks. Adverse events were recorded in 37 children, including 1 serious AE of an appendiceal neuroendocrine tumor. The most frequent AEs were hyperlipidemia (n = 13), acne (n = 12), and infections (n = 10, 5 of whom with herpes viruses).

Conclusions: Upadacitinib is an effective induction therapy for refractory pediatric UC and IBD-U. Efficacy should be weighed against the potential risks of AEs.

Keywords: Inflammatory bowel disease; JAK inhibitors; children.

© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

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Conflict of interest statement

Conflict of Interest

These authors disclose the following:

D.T.: Last 3 years, D.T. received consultation fee, research grant, royalties, or honorarium from Janssen, Pfizer, Shaare Zedek Medical Center, Hospital for Sick Children, Ferring, Abbvie, Takeda, Prometheus Biosciences, Lilly, SorrisoPharma, Boehringer Ingelheim, Galapagos, BMS, AlfaSigma MTD received consultant fees from Pfizer and BMS. M.G. is a Member of the CICRA Advisory Board (Crohn’s in Childhood Research Association). M.G. is currently involved in pharmaceutical trials sponsored by Abbvie. D.S.S. received lecturing fees from Takeda. M.B. received a consultant fee from Pfizer. O.H. received lectures/congress fees/consultancy from MSD, Abbvie, Takeda, Nutricia, Sandoz, Lilly. D.L.S.: Consultant: Pharming Pharm, Nestle. For the past 3 years, B.K. has received speaker fee, consultation fee, or research grant from Celltrion, Janssen, Abbvie, Takeda, Yuhan, Yungjin, JW Pharmaceutical, and Samsung Bioepis. H.H.U. has received research support or consultancy fees from J&J, Eli Lilly, Bristol Myers Squibb and AbbVie. HHU is supported by the National Institute for Health Research, Oxford Biomedical Research Centre, University of Oxford (HHU), and by The Leona M. and Harry B. Helmsley Charitable Trust. L.H.: received speaking fee from Abbvie. G.D.: Lectures/congress fees/consultancy: Nestlé Health Science and Pfizer.

Figures

**Figure 2**
A: Pediatric Ulcerative Colitis Activity Index (PUCAI) at baseline and at Week 8. B: Fecal calprotectin (FC) at baseline and at Week 8.

See this image and copyright information in PMC

References

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1. Atia O, Shavit-Brunschwig Z, Mould DR, et al. Outcomes, dosing, and predictors of vedolizumab treatment in children with inflammatory bowel disease (VEDOKIDS): a prospective, multicentre cohort study. Lancet Gastroenterol Hepatol 2023;8:31–42. - PubMed
1. Cohen S, Rolandsdotter H, Kolho KL, et al. Effectiveness and safety of ustekinumab in pediatric ulcerative colitis: a multi-center retrospective study from the pediatric IBD Porto Group of ESPGHAN. Paediatr Drugs 2024;26:609–17. - PMC - PubMed
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Upadacitinib for Induction of Remission in Pediatric Ulcerative Colitis: An International Multicenter Study

Affiliations

Upadacitinib for Induction of Remission in Pediatric Ulcerative Colitis: An International Multicenter Study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Supplementary concepts

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials