P1038Upadacitinib for maintenance treatment in pediatric ulcerative colitis: 52-week outcomes of an international multicenter retrospective study from the pediatric IBD Porto group of ESPGHAN

Abstract Background 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 a maintenance therapy in pediatric UC. Methods Children treated with upadacitinib for maintenance of remission of active UC or IBD-U from 35 centers affiliated with the Porto group of ESPGHAN were enrolled in this retrospective study. Data on demographic, clinical, laboratory, endoscopic, imaging and adverse events (AEs) data were recorded over 52 weeks of follow-up. The primary outcome of the study was sustained corticosteroid-free clinical remission (CFR), defined as CFR at both weeks 26 and 52. Disease activity was measured by the Pediatric Ulcerative Colitis Activity Index (PUCAI). Results A total of 105 children were included (95 UC and 10 IBD-U, mean age 14.6±3.3 years). Prior to upadacitinib, 103/105 (98%) children were treated with biologic therapies and 79 (75%) with ≥2 biologics. Clinical remission and CFR were observed after 8 weeks in 61 (58%) and 53 (51%) children, respectively (Figure 1). By week 52, 75 (71%) children achieved clinical remission and 73 (70%) CFR. Sustained CFR was recorded in 63 (60%) children. CFR with normal C-reactive protein was observed in 56% of children, and CFR with fecal calprotectin levels 150 mcg/g was observed in 38%, by week 52. A multivariable model incorporating baseline and week 8 variables revealed that prior failure of ≤ 2 biologic agents (OR = 6.67, 95% CI 1.64-20, P=0.008) and achieving week 8 CFR (OR = 29.70, 95% CI 7.86-112.30, P0.001) were independent predictors of sustained CFR. Receiver Operating Characteristic Curve analysis showed that week 8 PUCAI was the strongest predictor of sustained CFR, with an optimal cutoff of ≤ 5 (AUC = 0.80, 95% CI 0.70-0.90, P0.001; sensitivity 72%; specificity 82%; positive predictive value 87%; negative predictive value 63%, Figure 2). Sustained CFR in children weighing 40 kg was comparable to children weighing 40 kg (57% vs. 61%, P=0.765). Children 40 kg who achieved CFR at week 8 received numerically higher induction doses of upadacitinib per body surface area and per weight compared with those who did not achieve CFR 41.1 (29.1–44.2) vs. 34.3 (27.6–38.2) mg/m², P=0.276, and 1.4 (1.1–1.6) vs. 1.2 (1.1–1.4) mg/kg, P=0.258. Fifty-two (50%) children experienced AEs, two of which were considered as serious (an appendiceal neuroendocrine tumor and cytomegalovirus colitis). The most frequent AEs were hyperlipidemia (n = 20), infections (n = 18), and acne (n = 14). Conclusion Upadacitinib is an effective induction and maintenance therapy for refractory pediatric UC and IBD-U. Effectiveness should be weighed against the potential risks of AEs. Conflict of interest: Prof. Yerushalmy-Feler, Anat: No conflict of interest Spencer, Elizabeth: No conflict of interest Dubinsky, Marla C: Personal Fees: Consultant or Advisory Board: Abbvie, Abivax, Astra Zeneca, BMS, Celltrion, Gilead, Genentech, Janssen, Johnson and Johnson, Lilly, Merck, Pfizer, Prometheus Biosciences, Sanofi, Spyre, Target RWE, Takeda Other: Shareholder, Co-founder, Board of Directors of Trellus Health Co-Founder Mi Test Health Suskind, David L: a consultant for Nestle Health Science and Abbott Nutrition. Mitrova, Katarina: Lecture fees/consultancy: Abbvie, Janssen, Eli-Lilly Hradsky, Ondrej: Lectures/congress fees/consultancy from MSD, AbbVie, Takeda, Sandoz, Nutricia, Ferring, Pfizer, and Lilly. Conrad, Máire A: No conflict of interest Kelsen, Judith R: No conflict of interest Sładek, Malgorzata: lecture honorarium/travel grants from Abbvie, Sandoz, Nutrici Yeh, Pai-Jui: No conflict of interest Tzivinikos, Christos: Speaker honoraria by Abbvie, IPSEN, Sanofi, Mirum, Nutricia, Abbott, Novalac Advisory board fees by Abbott, Mirum, NAPO therapeutics, IPSEN, Nutricia, Nestle, novalac Henderson, Paul: Personal Fees: Speaker Honorarium from Vertex Pharmaceuticals Wlazło, Magdalena: No conflict of interest Hackl, Lukas: received a speaker fee for a single lecture from AbbVie Pharmaceuticals in 2023. Shouval, Dror: Lecturing fee - Takeda SAB - Tracells Mouratidou, Natalia: No conflict of interest Bramuzzo, Matteo: No conflict of interest Zuzej Urlep, Darja: No conflict of interest Olbjørn, Christine: Consulting and lecturing fees from Johnson & Johnson and Ferring. Mancuso, Giulia: No conflict of interest Schneider, Anna- Maria: No conflict of interest Pujol-Muncunill, Gemma: No conflict of interest Yogev, Dotan: No conflict of interest Kang, Ben: Other: For the past 3 years, Ben Kang has served as a speaker or consultant for Celltrion, Janssen, Eisai, Abbvie, Takeda, Yuhan, Yungjin, JW Pharmaceutical, and Samsung Bioepis and has received research funding from Celltrion. Gasparetto, Marco: is medical adviser of CICRA (Crohn’s in Childhood Research Association). He has been involved in commercial clinical trials sponsored by Abbvie. Rungø, Christine: No conflict of interest Romano, Claudio: No conflict of interest Martinelli, Massimo: No conflict of interest Kolho, Kaija-Leena: Grant: Pediatric Research Foundation Finland, Helsinki University Hospital Research Fund Personal Fees: Advisory Board Abbvie Finland and Biocodex, Consultancy Ferring Hojsak, Iva: Personal Fees: BioGaia, Biocodex, Abbott, Sandoz, Takeda, Ewopharma, Hipp, GM Pharma Norsa, Lorenzo: Consultant for PFIZER, NESTLE’, TAKEDA, ALFASIGMA, SANOFI Rinawi, Firas: No conflict of interest Sansotta, Naire: No conflict of interest Magen Rimon, Ramit: No conflict of interest Granot, Maya: No conflict of interest Scarallo, Luca: No conflict of interest Trindade, Eunice Claudia Moreno: None Velasco Rodríguez-Belvís, Marta: No conflict of interest Turner, Dan: Consultation fee: Janssen, Pfizer, Ferring, Abbvie, Takeda, Prometheus Biosciences, Lilly, SorrisoPharma, Boehringer Ingelheim, Galapagos, BMS, AlfaSigma, Merck, Gentech Research support: Janssen, Abbvie, Takeda, Pfizer Royalties: Shaare Zedek Medical Center, Hospital for Sick Children Cohen, Shlomi: No conflict of interest