J Crohns Colitis. 2024 Nov 28:jjae182. doi: 10.1093/ecco-jcc/jjae182. Online ahead of print.

Anat Yerushalmy-Feler ¹, Elizabeth A Spencer ², Michael T Dolinger ², David L Suskind ³, Katarina Mitrova ⁴, Ondrej Hradsky ⁴, Máire A Conrad ⁵, Judith R Kelsen ⁵, Holm H Uhlig ⁶, Christos Tzivinikos ⁷, Silvana Ancona ⁸, Magdalena Wlazlo ⁹, Lukas Hackl ¹⁰, Dror S Shouval ¹¹, Matteo Bramuzzo ¹², Darja Urlep ¹³, Christine Olbjorn ¹⁴, Giulia D'Arcangelo ¹⁵, Gemma Pujol-Muncunill ¹⁶, Dotan Yogev ¹⁷, Ben Kang ¹⁸, Marco Gasparetto ¹⁹, Christine Rungø ²⁰, Kaija-Leena Kolho ²¹, Iva Hojsak ²², Lorenzo Norsa ²³, Firas Rinawi ²⁴, Naire Sansotta ²⁵, Ramit Magen Rimon ²⁶, Maya Granot ²⁷, Luca Scarallo ²⁸, Eunice Trindade ²⁹, Marta Velasco Rodríguez-Belvís ³⁰, Dan Turner ¹⁷, Shlomi Cohen ¹

Author information

¹Pediatric 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.

²Division of Pediatric Gastroenterology, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

³University of Washington Medical School, Seattle, WA 98109, USA; Seattle Children's Hospital IBD Center, Seattle, WA 98105, USA.

⁴Department of Paediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.

⁵Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, PA, USA.

⁶Translational Gastroenterology Unit, University of Oxford, Oxford, United Kingdom; Biomedical Research Centre, University of Oxford, Oxford, United Kingdom; Department of Paediatrics, University of Oxford, Oxford, United Kingdom, Centre of Human Genetics, University of Oxford, Oxford, United Kingdom.

⁷Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates.

⁸Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Children and Young People, Edinburgh, Scotland.

⁹Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland.

¹⁰Department of Pediatrics I, Medical University Innsbruck, Innsbruck, Austria.

¹¹Institute of Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Petach Tikva, and Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

¹²Institute for Maternal and Child Health-IRCCS "Burlo Garofolo," Trieste, Italy.

¹³Department of Gastroenterology, Hepatology and Nutrition, University Children's Hospital Ljubljana, 1000, Ljubljana, Slovenia.

¹⁴Department of Paediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway.

¹⁵Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza-University of Rome, Rome, Italy.

¹⁶Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain.

¹⁷The Juliet Keidan Institute of Paediatric Gastroenterology and Nutrition, The Eisenberg R&D Authority, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.

¹⁸Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea.

¹⁹Norfolk and Norwich University Hospital, Jenny Lind Children's Hospital, and University of East Anglia, Norwich Medical School, Norwich, UK.

²⁰Department of Paediatric and Adolescence Medicine, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark.

²¹Department of Paediatric Gastroenterology, Children's Hospital, HUS and University of Helsinki, Helsinki, Finland.

²²Children's Hospital Zagreb, University of Zagreb Medical School, Zagreb, Croatia.

²³Pediatric Department, Children's Hospital Vittore Buzzi, University of Milan, Milan, Italy.

²⁴Pediatric Gastroenterology Unit and Faculty of Medicine Technion, Haifa, Emek Medical Centre, Afula, Israel.

²⁵Pediatric Hepatology, Gastroenterology and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy.

²⁶Pediatric Gastroenterology & Nutrition Institute, Ruth Rappaport Children's Hospital, Rambam Health Care Campus and the Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.

²⁷Pediatric Gastroenterology Unit, Edmond & Lily Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

²⁸Gastroenterology and Nutrition Unit, Meyer Children's Hospital, Florence, Italy.

²⁹Pediatric Gastroenterology and Nutrition Unit, Centro Hospitalar Universitário São João, Porto, Portugal.

³⁰Department of Pediatric Gastroenterology and Nutrition, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.

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. AEs were recorded in 37 children, including one serious AE of an appendiceal neuroendocrine tumor. The most frequent AEs were hyperlipidemia (n=13), acne (n=12), and infections (n=10, five of whom with herpes viruses).

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