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.

Al Jalila Children's Specialty Hospital Dubai UAE

Biomedical Research Centre University of Oxford Oxford UK

Centre of Human Genetics University of Oxford Oxford UK

Children's Hospital Zagreb University of Zagreb Medical School Zagreb Croatia

Department of Gastroenterology Hepatology and Nutrition University Children's Hospital Ljubljana Ljubljana Slovenia

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

Department of Paediatric and Adolescence Medicine Copenhagen University Hospital Amager and Hvidovre Hvidovre Denmark

Department of Paediatric and Adolescent Medicine Akershus University Hospital Lørenskog Norway

Department of Paediatric Gastroenterology and Nutrition Royal Hospital for Children and Young People Edinburgh Scotland UK

Department of Paediatric Gastroenterology Children's Hospital HUS Helsinki Finland

Department of Paediatrics 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic

Department of Paediatrics University of Oxford Oxford UK

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

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

Department of Pediatrics 1 Medical University Innsbruck Innsbruck Austria

Department of Pediatrics School of Medicine Kyungpook National University Daegu Korea

Division of Gastroenterology Hepatology and Nutrition Children's Hospital of Philadelphia Perelman School of Medicine at the University of Pennsylvania Philadelphia Pennsylvania USA

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

Faculty of Medicine Technion Haifa Israel

Faculty of Medicine Technion Israel Institute of Technology Haifa Israel

Faculty of Medicine Tel Aviv University Tel Aviv Israel

Gastroenterology and Nutrition Unit Meyer Children's Hospital IRCCS Florence Italy

Institute for Maternal and Child Health IRCCS Burlo Garofolo Trieste Italy

Institute of Gastroenterology Nutrition and Liver Diseases Schneider Children's Medical Center of Israel Petach Tikva Israel

Jenny Lind Children's Hospital Norfolk and Norwich University Hospitals Norwich UK

Norwich Medical School University of East Anglia Norwich UK

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

Pediatric Gastroenterology and Liver Unit Maternal and Child Health Department Sapienza University of Rome Rome Italy

Pediatric Gastroenterology and Nutrition Institute Ruth Rappaport Children's Hospital Rambam Health Care Campus Israel Institute of Technology Haifa Israel

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

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

Pediatric Gastroenterology Unit Edmond and Lily Safra Children's Hospital Sheba Medical Center Ramat Gan Israel

Pediatric Gastroenterology Unit Emek Medical Centre Afula Israel

Pediatric Hepatology Gastroenterology and Transplantation ASST Papa Giovanni XXIII Bergamo Italy

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

The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition Shaare Zedek Medical Center The Hebrew University of Jerusalem Jerusalem Israel

Translational Gastroenterology Unit University of Oxford Oxford UK

University of Helsinki Helsinki Finland

University of Washington Medical School Seattle Washington USA

Zobrazit více v PubMed

van Rheenen P. F., Aloi M., Assa A., et al., “The Medical Management of Paediatric Crohn's Disease: An ECCO‐ESPGHAN Guideline Update,” Journal of Crohn's & Colitis 15, no. 2 (2020): jjaa161, 10.1093/ecco-jcc/jjaa161. PubMed DOI

Atia O., Shavit‐Brunschwig Z., Mould D. R., et al., “Outcomes, Dosing, and Predictors of Vedolizumab Treatment in Children With Inflammatory Bowel Disease (VEDOKIDS): A Prospective, Multicentre Cohort Study,” Lancet Gastroenterology & Hepatology 8 (2023): 31–42. PubMed

Yerushalmy‐Feler A., Pujol‐Muncunill G., Martin‐de‐Carpi J., et al., “Safety and Potential Efficacy of Escalating Dose of Ustekinumab in Pediatric Crohn Disease (The Speed‐Up Study): A Multicenter Study From the Pediatric IBD Porto Group of ESPGHAN,” Journal of Pediatric Gastroenterology and Nutrition 75, no. 6 (2022): 717–723. PubMed

Honap S., Danese S., and Peyrin‐Biroulet L., “Are All Janus Kinase Inhibitors for Inflammatory Bowel Disease the Same?,” Gastroenterology & Hepatology 19, no. 12 (2023): 727–738. PubMed PMC

Danese S., Vermeire S., Zhou W., et al., “Upadacitinib as Induction and Maintenance Therapy for Moderately to Severely Active Ulcerative Colitis: Results From Three Phase 3, Multicentre, Doubleblind, Randomised Trials,” Lancet 399 (2022): 2113–2128. PubMed

Panés J., Loftus E. V., Higgins P. D. R., et al., “Induction and Maintenance Treatment With Upadacitinib Improves Health‐Related Quality of Life in Patients With Moderately to Severely Active Ulcerative Colitis: Phase 3 Study Results,” Inflammatory Bowel Diseases 29 (2023): 1421–1430. PubMed PMC

Vermeire S., Danese S., Zhou W., et al., “Efficacy and Safety of Upadacitinib Maintenance Therapy for Moderately to Severely Active Ulcerative Colitis in Patients Responding to 8 Week Induction Therapy (U‐ACHIEVE Maintenance): Overall Results From the Randomised, Placebo‐Controlled, Double‐Blind, Phase 3 Maintenance Study,” Lancet Gastroenterology & Hepatology 8 (2023): 976–989. PubMed

L. EV, Jr. , Panés J., Lacerda A. P., et al., “Upadacitinib Induction and Maintenance Therapy for Crohn's Disease,” New England Journal of Medicine 388 (2023): 1966–1980. PubMed

D'Haens G., Panés J., Louis E., et al., “Upadacitinib Was Efficacious and Well‐Tolerated Over 30 Months in Patients With Crohn's Disease in the CELEST Extension Study,” Clinical Gastroenterology and Hepatology 20 (2022): 2337–2346. PubMed

Spencer E. A., Bergstein S., Dolinger M., et al., “Single‐Center Experience With Upadacitinib for Adolescents With Refractory Inflammatory Bowel Disease,” Inflammatory Bowel Diseases 30 (2023): izad300, 10.1093/ibd/izad300. PubMed DOI

Yerushalmy‐Feler A., Olbjorn C., Kolho K. L., et al., “Dual Biologic or Small Molecule Therapy in Refractory Pediatric Inflammatory Bowel Disease (DOUBLE‐PIBD): A Multicenter Study From the Pediatric IBD Porto Group of ESPGHAN,” Inflammatory Bowel Diseases 30 (2024): 159–166. PubMed

Kellar A., Dolinger M. T., Spencer E. A., and Dubinsky M. C., “Real‐World Outcomes of Dual Advanced Therapy in Children and Young Adults With Inflammatory Bowel Disease,” Digestive Diseases and Sciences 69, no. 5 (2024): 1826–1833. PubMed

Paller A. S., Ladizinski B., Mendes‐Bastos P., et al., “Efficacy and Safety of Upadacitinib Treatment in Adolescents With Moderate‐To‐Severe Atopic Dermatitis: Analysis of the Measure Up 1, Measure Up 2, and AD Up Randomized Clinical Trials,” JAMA Dermatology 159 (2023): 526–535. PubMed PMC

U.S. Food and Drug Administration. RINVOQ , (upadacitinib) drug label. (2022), https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/211675s003lbl.pdf.

Qian Y., Raymundo E. M., Hao S., et al., “Pharmacokinetics, Safety, Tolerability, and Exploratory Efficacy of Upadacitinib in Children With Severe Atopic Dermatitis,” Clinical Therapeutics 46 (2024): 733–741. PubMed

Levine A., Koletzko S., Turner D., et al., “Revised Porto Criteria for the Diagnosis of Inflammatory Bowel Disease in Children and Adolescents,” Journal of Pediatric Gastroenterology and Nutrition 58, no. 6 (2014): 795–806. PubMed

Turner D., Griffiths A. M., Walters T. D., et al., “Mathematical Weighting of the Pediatric Crohn's Disease Activity Index (PCDAI) and Comparison With Its Other Short Versions,” Inflammatory Bowel Diseases 18, no. 1 (2012): 55–62. PubMed

Levine A., Griffiths A., Markowitz J., et al., “Pediatric Modification of the Montreal Classification for Inflammatory Bowel Disease: The Paris Classification,” Inflammatory Bowel Diseases 17, no. 6 (2011): 1314–1321. PubMed

Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents and National Heart, Lung, and Blood Institute , “Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Summary Report,” Pediatrics 128, no. 5 (2011): S213–S256. PubMed PMC

Friedberg S., Choi D., Hunold T., et al., “Upadacitinib Is Effective and Safe in Both Ulcerative Colitis and Crohn's Disease: Prospective Real‐World Experience,” Clinical Gastroenterology and Hepatology 21, no. 7 (2023): 1913–1923. PubMed PMC

Elford A. T., Bishara M., Plevris N., et al., “Real‐World Effectiveness of Upadacitinib in Crohn's Disease: A UK Multicentre Retrospective Cohort Study,” Frontline Gastroenterology 15, no. 4 (2024): 297–304. PubMed PMC

Chugh R., Braga‐Neto M. B., Fredrick T. W., et al., “Multicentre Real‐World Experience of Upadacitinib in the Treatment of Crohn's Disease,” Journal of Crohn's & Colitis 17, no. 4 (2023): 504–512. PubMed

Niu C., Zhang J., Napel M., et al., “Systematic Review With Meta‐Analysis: Efficacy and Safety of Upadacitinib in Managing Moderate‐To‐Severe Crohn's Disease and Ulcerative Colitis,” Clinical Drug Investigation 44, no. 6 (2024): 371–385. PubMed

Attauabi M., Steenholdt C., Poulsen A., et al., “Network Meta‐Analysis: Comparative Onset of Early Effect of Biologics and Small Molecules in Moderately to Severely Active Luminal Crohn's Disease,” Alimentary Pharmacology & Therapeutics 60, no. 2 (2024): 124–143. PubMed

Peyrin‐Biroulet L., Louis E., E. V. Loftus, Jr. , et al., “Quality of Life and Work Productivity Improvements With Upadacitinib: Phase 2b Evidence From Patients With Moderate to Severe Crohn's Disease,” Advances in Therapy 38, no. 5 (2021): 2339–2352. PubMed PMC

Colombel J. F., Lacerda A. P., Irving P. M., et al., “Efficacy and Safety of Upadacitinib for Perianal Fistulizing Crohn's Disease: A Post Hoc Analysis of 3 Phase 3 Trials,” Clinical Gastroenterology and Hepatology (2024): S1542‐3565(24)00860, 10.1016/j.cgh.2024.08.032. PubMed DOI

Bhatnagar S., Schlachter L., Eckert D., et al., “Pharmacokinetics and Exposure‐Response Analyses to Support Dose Selection of Upadacitinib in Crohn's Disease,” Clinical Pharmacology and Therapeutics 116 (2024): 1240–1251, 10.1002/cpt.3359. PubMed DOI

Miyatani Y., Choi D., Choi N. K., and Rubin D. T., “Dual‐Targeted Therapy With Upadacitinib and Ustekinumab in Medically Complex Crohn's Disease,” Digestive Diseases and Sciences 69, no. 2 (2024): 355–359. PubMed

Peyrin‐Biroulet L., Panaccione R., Louis E., et al., “Upadacitinib Achieves Clinical and Endoscopic Outcomes in Crohn's Disease Regardless of Prior Biologic Exposure,” Clinical Gastroenterology and Hepatology 22, no. 10 (2024): S1542‐3565(24)00253–2, 10.1016/j.cgh.2024.02.026. PubMed DOI

Colombel J. F., Hisamatsu T., Atreya R., et al., “Upadacitinib Reduces Crohn's Disease Symptoms Within the First Week of Induction Therapy,” Clinical Gastroenterology and Hepatology 22, no. 8 (2024): 1668–1677. PubMed

Ghosh S., Feagan B. G., Parra R. S., et al., “Impact of Upadacitinib Induction and Maintenance Therapy on Health‐Related Quality of Life, Fatigue, and Work Productivity in Patients With Moderately‐to‐severely Active Crohn's Disease,” Journal of Crohn's & Colitis 18, no. 11 (2024): jjae083, 10.1093/ecco-jcc/jjae083. PubMed DOI PMC

Pokryszka J., Reinisch S., Primas C., Novacek G., and Reinisch W., “Induction Efficacy of Upadacitinib in Therapy‐Refractory Crohn's Disease: A Retrospective Case Series,” Clinical Gastroenterology and Hepatology 21, no. 2 (2023): 532–534.e3. PubMed

Traboulsi C., Ayoub F., Silfen A., Rodriguez T. G., and Rubin D. T., “Upadacitinib Is Safe and Effective for Crohn's Disease: Real‐World Data From a Tertiary Center,” Digestive Diseases and Sciences 68, no. 2 (2023): 385–388. PubMed

European Medicines Agency , “EMA Recommends Measures to Minimise Risk of Serious Side Effects With Janus Kinase Inhibitors for Chronic Inflammatory Disorders,” 2022, https://www.ema.europa.eu/en/news/ema‐recommends‐measures‐minimise‐risk‐serious‐side‐effects‐janus‐kinase‐inhibitors‐chronic‐inflammatory‐disorders.