Abstract Background Data on upadacitinib therapy in children with Crohn’s disease (CD) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as a 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 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 of therapy. Disease activity was measured by the weighted Pediatric Crohn’s Disease Activity Index (wPCDAI). Results A total of 120 children were included (mean age 15.4±2.5 years). Prior to upadacitinib, 119/120 (99%) children were treated with biologic therapies and 104 (87%) with ≥2 biologics. Clinical remission and CFR were observed after 8 weeks in 77 (64%) and 72 (60%) children, respectively (Figure 1). By week 52, 74 (62%) children achieved clinical remission and CFR. Sustained CFR was recorded in 66 (55%) children. CFR with normal C-reactive protein was observed in 50% of children and CFR with fecal calprotectin level 150 mcg/g was observed in 33%, by week 52. A multivariable model incorporating baseline and week 8 variables revealed that prior failure of ≤ 2 biologic agents (OR = 3.22, 95% CI 1.08-10, P=0.037) and week 8 CFR (OR = 4.43, 95% CI 1.44-13.65, P=0.010) were independent predictors of sustained CFR. Receiver Operating Characteristic Curve analysis showed that week 8 wPCDAI was the strongest predictor of sustained CFR, with an optimal cutoff of ≤ 10 (AUC = 0.74, 95% CI 0.63-0.85, P 0.001; sensitivity 75%; specificity 69%; positive predictive value 73%; negative predictive value 70%, Figure 2). Sustained CFR in children weighing 40 kg was comparable to children weighing 40 kg (55% vs. 55%, P=0.962). The dosing of children 40 kg who achieved sustained CFR was comparable to children who did not. Fifty-three (44%) children experienced AEs, two of which were considered as 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. Conflict of interest: Spencer, Elizabeth: Advisory board for Celltrion. Cohen, Shlomi: 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: is 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 eh, Pai-Jui Y: 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. D’Orsi, Miriam: No conflict of interest Schneider, Anna- Maria: No conflict of interest Pujol Muncunill, Gemma: No conflict of interest Gotsdiner, Liora: 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: No conflict of interest 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: No conflict of interest 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 Prof. Yerushalmy-Feler, Anat: No conflict of interest
Spencer et al. (Thu,) studied this question.