Multicenter Study

. 2025 Apr;61(8):1372-1380.

doi: 10.1111/apt.70016. Epub 2025 Feb 8.

Upadacitinib for Induction of Remission in Paediatric Crohn's Disease: An International Multicentre Retrospective Study

Shlomi Cohen¹, Elizabeth A Spencer², Michael T Dolinger², David L Suskind³, Katarina Mitrova⁴, Ondrej Hradsky⁴, Máire A Conrad⁵, Judith R Kelsen⁵, Holm H Uhlig^{6

7

8

9}, Christos Tzivinikos¹⁰, Paul Henderson¹¹, Magdalena Wlazlo¹², Lukas Hackl¹³, Dror S Shouval^{14

15}, Matteo Bramuzzo¹⁶, Darja Urlep¹⁷, Christine Olbjørn¹⁸, Giulia D'Arcangelo¹⁹, Gemma Pujol-Muncunill²⁰, Dotan Yogev²¹, Ben Kang²², Marco Gasparetto^{23

24}, Christine Rungoe²⁵, Kaija-Leena Kolho^{26

27}, Iva Hojsak²⁸, Lorenzo Norsa²⁹, Firas Rinawi^{30

31}, Naire Sansotta³², Ramit Magen Rimon^{33

34}, Maya Granot^{1

35}, Luca Scarallo³⁶, Eunice Trindade³⁷, Marta Velasco Rodríguez-Belvís³⁸, Dan Turner³⁹, Anat Yerushalmy-Feler¹

Affiliations

¹ Pediatric Gastroenterology Institute, "Dana-Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel and the Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
² Division of Pediatric Gastroenterology, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
³ University of Washington Medical School, Seattle, Washington, USA.
⁴ Department of Paediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
⁵ Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁶ Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
⁷ Biomedical Research Centre, University of Oxford, Oxford, UK.
⁸ Department of Paediatrics, University of Oxford, Oxford, UK.
⁹ Centre of Human Genetics, University of Oxford, Oxford, UK.
¹⁰ Al Jalila Children's Specialty Hospital, Dubai, UAE.
¹¹ Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Children and Young People, Edinburgh, Scotland, UK.
¹² Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland.
¹³ Department of Pediatrics I, Medical University Innsbruck, Innsbruck, Austria.
¹⁴ Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
¹⁵ Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
¹⁶ Institute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy.
¹⁷ Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital Ljubljana, Ljubljana, Slovenia.
¹⁸ Department of Paediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway.
¹⁹ Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza-University of Rome, Rome, Italy.
²⁰ Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain.
²¹ The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
²² Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea.
²³ Jenny Lind Children's Hospital, Norfolk and Norwich University Hospitals, Norwich, UK.
²⁴ Norwich Medical School, University of East Anglia, Norwich, UK.
²⁵ Department of Paediatric and Adolescence Medicine, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
²⁶ Department of Paediatric Gastroenterology, Children's Hospital HUS, Helsinki, Finland.
²⁷ 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, Emek Medical Centre, Afula, Israel.
³¹ Faculty of Medicine Technion, Haifa, Israel.
³² Pediatric Hepatology, Gastroenterology and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy.
³³ Pediatric Gastroenterology & Nutrition Institute, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Israel Institute of Technology, Haifa, Israel.
³⁴ Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
³⁵ Pediatric Gastroenterology Unit, Edmond & Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel.
³⁶ Gastroenterology and Nutrition Unit, Meyer Children's Hospital IRCCS, Florence, Italy.
³⁷ Pediatric Gastroenterology and Nutrition Unit, Centro Hospitalar Universitário São João, Porto, Portugal.
³⁸ Department of Pediatric Gastroenterology and Nutrition, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
³⁹ 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.

PMID: 39921898
PMCID: PMC11950809
DOI: 10.1111/apt.70016

Multicenter Study

Upadacitinib for Induction of Remission in Paediatric Crohn's Disease: An International Multicentre Retrospective Study

Shlomi Cohen et al. Aliment Pharmacol Ther. 2025 Apr.

. 2025 Apr;61(8):1372-1380.

doi: 10.1111/apt.70016. Epub 2025 Feb 8.

Authors

Affiliations

¹ Pediatric Gastroenterology Institute, "Dana-Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel and the Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
² Division of Pediatric Gastroenterology, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
³ University of Washington Medical School, Seattle, Washington, USA.
⁴ Department of Paediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
⁵ Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁶ Translational Gastroenterology Unit, University of Oxford, Oxford, UK.
⁷ Biomedical Research Centre, University of Oxford, Oxford, UK.
⁸ Department of Paediatrics, University of Oxford, Oxford, UK.
⁹ Centre of Human Genetics, University of Oxford, Oxford, UK.
¹⁰ Al Jalila Children's Specialty Hospital, Dubai, UAE.
¹¹ Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Children and Young People, Edinburgh, Scotland, UK.
¹² Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland.
¹³ Department of Pediatrics I, Medical University Innsbruck, Innsbruck, Austria.
¹⁴ Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
¹⁵ Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
¹⁶ Institute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy.
¹⁷ Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital Ljubljana, Ljubljana, Slovenia.
¹⁸ Department of Paediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway.
¹⁹ Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza-University of Rome, Rome, Italy.
²⁰ Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain.
²¹ The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
²² Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea.
²³ Jenny Lind Children's Hospital, Norfolk and Norwich University Hospitals, Norwich, UK.
²⁴ Norwich Medical School, University of East Anglia, Norwich, UK.
²⁵ Department of Paediatric and Adolescence Medicine, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
²⁶ Department of Paediatric Gastroenterology, Children's Hospital HUS, Helsinki, Finland.
²⁷ 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, Emek Medical Centre, Afula, Israel.
³¹ Faculty of Medicine Technion, Haifa, Israel.
³² Pediatric Hepatology, Gastroenterology and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy.
³³ Pediatric Gastroenterology & Nutrition Institute, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Israel Institute of Technology, Haifa, Israel.
³⁴ Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
³⁵ Pediatric Gastroenterology Unit, Edmond & Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel.
³⁶ Gastroenterology and Nutrition Unit, Meyer Children's Hospital IRCCS, Florence, Italy.
³⁷ Pediatric Gastroenterology and Nutrition Unit, Centro Hospitalar Universitário São João, Porto, Portugal.
³⁸ Department of Pediatric Gastroenterology and Nutrition, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
³⁹ 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.

PMID: 39921898
PMCID: PMC11950809
DOI: 10.1111/apt.70016

Abstract

Background: There are scarce data available on upadacitinib in children with Crohn's disease (CD).

Aim: To evaluate the effectiveness and safety of upadacitinib as an induction therapy in paediatric CD.

Methods: This was a multicentre retrospective study between 2022 and 2024 of children treated with upadacitinib for induction of remission of active CD conducted in 30 centres worldwide affiliated with the IBD Interest and Porto group of the ESPGHAN. We recorded demographic, clinical and laboratory data and adverse events (AEs) at week 8 post-induction. The analysis of the primary outcome was based upon the intention-to-treat (ITT) principle.

Results: We included 100 children (median age 15.8 [interquartile range 14.3-17.2]). All were previously treated with biologic therapies including 89 with ≥ 2 biologics. At the end of the 8-week induction period, we observed clinical response, clinical remission and corticosteroid- and exclusive enteral nutrition-free clinical remission (CFR) in 75%, 56% and 52%, respectively. By the end of induction, 68% had achieved normalisation of C-reactive protein, and 58% had faecal calprotectin (FC) < 150 mcg/g. There was combined CFR and FC remission in 13/31 children with available data at 8 weeks (13% of the ITT population). AEs were recorded in 24 children; the most frequent was acne in 12. Two AEs (severe acne and hypertriglyceridemia) led to discontinuation of therapy.

Conclusion: Upadacitinib is an effective induction therapy for refractory paediatric CD. Efficacy should be weighed against the potential risks of AEs.

Keywords: JAK inhibitors; children; inflammatory bowel disease.

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Conflict of interest statement

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. M.T.D. 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 (including M14‐671). D.S.S. received lecturing fees from Takeda. M.V.R‐B. received a consultant fee from Pfizer. O.H. received lectures/congress fees/consultancy from MSD, Abbvie, Takeda, Nutricia, Sandoz, Lilly, Pfizer. 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. H.H.U. is supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) 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. I.H. received lecture/consultation fee from Abbot, Pfizer, Nestle, Oktal‐Pharma, Takeda. K.L.K.: received consultant/lecture fees from Abbvie, Biocodex and Ferring. P.H. is supported by an NRS Clinician Fellowship. L.N.: received consultant or advisory board honoraria by Takeda, Nestlè, Danone, Sanofi, Zealand.

Figures

**FIGURE 1**
(A) wPCDAI at baseline and at week 8. (B) Faecal calprotectin at baseline and at week 8.

See this image and copyright information in PMC

References

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Upadacitinib for Induction of Remission in Paediatric Crohn's Disease: An International Multicentre Retrospective Study

Affiliations

Upadacitinib for Induction of Remission in Paediatric Crohn's Disease: An International Multicentre Retrospective Study

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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Supplementary concepts

Grants and funding

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