BACKGROUND: Data on upadacitinib therapy for pediatric acute severe ulcerative colitis (ASC) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as a salvage therapy in pediatric ASC. METHODS: Children and adolescents with ASC who were treated with upadacitinib for the induction of remission were enrolled in this retrospective multicenter study. Demographic, clinical, and laboratory data as well as adverse events (AEs) were recorded after the 8-week induction period and throughout 26 weeks of therapy. Analyses were based on the intention-to-treat principal. RESULTS: Twenty-two patients were included (median age 15.7 [interquartile range 13.5-16.6] years, 12 hospitalized), all with anti-tumor necrosis factor (TNF) therapy refractory disease. Ten patients were treated with corticosteroids at baseline, and upadacitinib was added to an ongoing biologic therapy in five patients. At week 8 of therapy, 11 (50%) patients of the cohort remained colectomy-free and in corticosteroid-free clinical remission (CFR), and 17 (77%) patients remained colectomy-free. Normal C-reactive protein (CRP) was achieved in 9 of 11 (82%) patients who were in CFR, and fecal calprotectin <150 mcg/g in 4 of 6 (67%) patients with available data. By week 26, 14 (64%) were in CFR and 16 (73%) patients remained colectomy-free. All these patients had normal CRP levels, and 4 of 7 patients with available data had fecal calprotectin <150 mcg/g. Twelve patients reported AEs, including two serious AEs of an appendiceal neuroendocrine tumor and cytomegalovirus colitis. CONCLUSION: Upadacitinib is an effective induction therapy for children and adolescents with ASC after failing anti-TNF.

This multicenter study describes 22 children with ASC treated with upadacitinib. Clinical remission was observed in 12 (55%) patients, and 11 (50%) were in colectomy-free, corticosteroid-free remission (CFR) after 8 weeks. By week 26, 14 (64%) patients were in CFR.

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

Department of Pediatrics Stanford University School of Medicine Stanford CA United States

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

Gray Faculty of Medical and Health Sciences Tel Aviv University Tel Aviv Israel

Institute for Maternal and Child Health IRCCS Burlo Garofolo Trieste Italy

Pediatric Gastroenterology Unit Dana Dwek Children's Hospital Tel Aviv Sourasky Medical Center Tel Aviv Israel

The Faculty of Medicine Technion Israel Institute of Technology Haifa Israel

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

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