Upadacitinib treatment in pediatric Crohn’s disease: 52-week outcomes of an international multicenter retrospective cohort study from the pediatric IBD Porto Group of ESPGHAN

BACKGROUND AND AIMS: Data on upadacitinib maintenance therapy in pediatric Crohn's disease (CD) are scarce. We aimed to evaluate the effectiveness, safety, and dosing of upadacitinib as maintenance therapy in pediatric CD. METHODS: Children treated with upadacitinib for maintenance of remission of active CD from 35 centers affiliated with the Porto Group of ESPGHAN were included in this retrospective cohort study. Data on demographic, clinical, laboratory, endoscopic, and imaging findings and on adverse events (AEs) were recorded over 52 weeks of follow-up. RESULTS: A total of 120 children were included (91 receiving upadacitinib as monotherapy and 29 as combination advanced therapy, mean age 15.4 ± 2.5 years). Prior to upadacitinib induction, 119/120 (99%) children had been treated with biologic therapies, 104 (87%) with two or more biologics and 98 (82%) had failed both vedolizumab and ustekinumab. Clinical remission and corticosteroid-free clinical remission (CFR) were observed after upadacitinib induction in 77 (64%) and 72 (60%) children, respectively. By week 52, 74 (62%) children achieved both clinical remission and CFR, and CFR was sustained in 66 (55%) children. CFR with normal C-reactive protein levels was achieved in 50% of children and CFR with fecal calprotectin levels <150 µg/g was achieved in 33% of children by week 52. Fifty-three (44%) children sustained AEs, two of which were serious (severe acne and intestinal perforation). The most frequent AEs were acne (n = 23), hyperlipidemia (n = 18), and infections (n = 14). CONCLUSION: Upadacitinib is an effective maintenance therapy for refractory pediatric CD. Effectiveness should be weighed against the potential risks of AEs.