DOP035 Upadacitinib: Personalized Goals for Remission and Disease Evaluation in Patients with Crohn’s Disease (UPGRADE-CD) - A Multicenter Prospective Study from the Italian Group for the Study of Inflammatory Bowel Diseases (IG-IBD).

Abstract Background Crohn’s disease (CD) is a chronic, relapsing inflammatory disorder often resistant to therapies. While upadacitinib (UPA) has shown promise in registration trials, real-world data are scarce. UPGRADE-CD study, promoted by IG-IBD, was designed to assess UPA effectiveness and safety in refractory CD. Methods This is a preliminary analysis of a prospective, multicenter, observational study enrolling consecutive adults patients with refractory CD from Italian referral centers. Patients were treated with UPA and evaluated with standardized clinical (Harvey-Bradshaw Index, HBI), endoscopic (Simple Endoscopic Score for Crohn’s Disease, SES-CD), and biochemical [C-Reactive Protein (CRP), fecal calprotectin] parameters at baseline, 3, and 6 months; 12-month follow-up data collection is still ongoing. Primary endpoints: clinical response (HBI decrease ≥3), clinical remission (HBI < 5), and their steroid-free equivalents. Secondary endpoints were endoscopic improvement (≥50% SES-CD reduction or ≥ 2-point drop if baseline SES-CD = 4) and endoscopic remission (SES-CD ≤ ssss2). Dropouts were counted as non-responders from discontinuation onward, and missing data excluded. Analyses were performed using R software. Results Overall, 309 patients were included. Demographics characteristics are reported in Table 1. Clinical response rates remained high at 3 and 6 months (58.3% and 62.1%, p < 0.001). Clinical remission showed similar proportions (54.7%, 57.5% p < 0.001). Steroid-free clinical response was achieved in 52.5% at 3 months and 51.1% at 6 months, whereas steroid-free clinical remission rates were 47.9% and 46.6% at 3 and 6 months, respectively. Endoscopic improvement increased over time from 20.0% at 3 months to 43.5% at 6 months (p < 0.001), with endoscopic remission occurring in 40.1% of patients at 6 months (p < 0.01). Mean fecal calprotectin remained above normal but trended lower (from 986.7± 1619.9 at baseline to 362.0 ± 743.3 at 6 months, p < 0.001). Mean CRP levels declined significantly over time (from 62.3±197.4 mg/L at baseline to 17.1±37.2 mg/L at 6 months, p < 0.001). UPA was discontinued in 18 patients by month 3 and 21 patients by 6 months due to inefficacy or adverse events (6/18 and 7/21 at 3 and 6 months, respectively). Conclusion In this preliminary real-world analysis, UPA induced high clinical and steroid-free remission rates and improved endoscopic outcomes over 6 months in refractory CD, with a favorable safety profile and low discontinuation rates. Extended follow-up will clarify long-term effectiveness and safety. Conflict of interest: Barberio, Brigida: Brigida Barberio: has served as speaker for Abbvie, Agave, Alfasigma, AGpharma, Johnson & Johnson, Eli Lilly, MSD, Pfizer, Procise, Sofar, Takeda, Unifarco. BB has served as consultant for Abbvie, Eli Lilly, ohnson & Johnson. Scaldaferri, Franco: Consultancy fee/board for Janseen, Takeda, Pfizer, MSD, Sandoz, Galapagos, Celltrion, Ferring, Abbvie, Lilly, Alfasigma, Abivax Bezzio, Cristina: Personal Fees: I received consulting/advisory board/lecture fees from Alfa Sigma, AbbVie, Celltrion, Eli Lilly, Ferring, Gilead, Johnson & Johnson MSD, Pfizer and Takeda Dragoni, Gabriele: Grant: ECCO Grant 2020 ECCO/AOCC Travel Grant 2021 ECCO IIS Registry Grant 2023 ECCO/IBUS Research Grant 2023 Personal Fees: - Speaker’s fees from: 2020: Novartis 2022: Janssen 2023: Alfasigma, Janssen, Pfizer, and Takeda 2024: Ferring, Johnson & Johnson, Eli Lilly, Pfizer, and Takeda 2025: Abbvie, Alfasigma, Ferring, Eli Lilly, LionHealth, Pfizer, Takeda - Advisory board fees from: 2023: Celltrion Healthcare and Pfizer 2024: AbbVie 2025: AbbVie, Johnson & Johnson Viola, Anna: No conflict of interest Todeschini, Alessia: The author has served as a consultant and/or received lecture fees from Abbvie, Alfasigma, Celltrion, Johnson & Johnson, Ely Lilly, Ferring, Lion Health,Takeda. Principi, Maria Beatrice: No conflict of interest Onali, Sara: Consultant/lecture fees to: Abbvie, Alfasigma, MSD, Takeda, J & J, Galapagos, Pfizer, Eli Lilly D’Amico, Ferdinando: Grant: ECCO fellowship grant 2020 ECCO grant 2021 Personal Fees: F D’Amico has served as a speaker for Abbvie, Alfasigma, Ferring, Lilly, Sandoz, Janssen, Fresenius Kabi, Galapagos, Giuliani, MSD, Pfizer, Takeda, Tillotts, and Omega Pharma he also served as an advisory board member for Abbvie, AnaptysBio, Ferring, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Takeda, and Nestlè. Viganò, Chiara: Consultancy and lecture fees from: AbbVie, Galapagos, Janssen-Cilag, Johnson & Johnson, Pfizer, Takeda, Celltrion, Alfasigma, Eli Lilly and research grant from Celltrion and Pfizer. Cappello, Maria: None Mocci, Giammarco: No conflict of interest Viscido, Angelo: none Bodini, Giorgia: No conflict of interest Ribaldone, Davide Giuseppe: Davide Giuseppe Ribaldone declares the following paid consultancies, lecture fees for the past two years: Johnson & Johnson, Takeda, Celltrion, Alfasigma, Pfizer, Eli Lilly, Abbvie, Sandoz Marafini, Irene: Irene Marafini served as advisory board member for Abbvie, Eli Lilly, Galapagos and received speaker honoraria from Abbvie and Eli Lilly Pugliese, Daniela: Consultant/Lectures fees from: AbbVie, Takeda, Johnson, Pfizer, Alfasigma, MSD, Lilly, Celltrion. Massari, Alessandro: No conflict of interest Saibeni, Simone: Consultancy, lecture fees, and advisory board for AbbVie, Alfasigma, Arena, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, Johnson & Johnson, MSD, Pfizer, and Takeda. Pastorelli, Luca: Luca Pastorelli served as consultant for Giuliani, received lecture fees and/or advisory board fees from Abbvie, Takeda, Ferring, Pfizer, Sandoz, Janssen, Johnson & Johnson, Galapagos, Arena, Eli-Lilly Rizzello, Fernando: No conflict of interest Bergna, Irene Maria Bambina: None Gravina, Antonietta Gerarda: Gravina AG has conducted training activities [e.g. educational continuing medical activities (ECM), preceptorship] for Pfizer, Galapagos Biopharma, and AbbVie. Desideri, Federico: No conflict of interest Merli, Manuela: No conflict of interest Bertani, Lorenzo: No conflict of interest Spagnuolo, Rocco: no Imperatore, Nicola: None to declare Ferracane, Concetta: nothing to declare Quadarella, Alessandro: I have no conflict of interest. Di Luna, Imma: No conflict of interest Tortorella, Vincenza: Nessuno Mazzuoli, Silvia: No conflict of interest Felice, Carla: Advisory board for AbbVie, MSD, J & J. Balestrieri, Paola: Advisory board for Alfasigma- Janssen- Abbvie- Takeda- Eli Lilly Balducci, Daniele: none Aratari, Annalisa: Consultant or Advisory board member (in the last two years) for Takeda,Abbvie,Pfizer,Galapagos De Barba, Caterina: No conflict of interest Zingone, Fabiana: No conflict of interest Savarino, Edoardo Vincenzo: Personal Fees: Takeda, Abbvie, MSD, Janssen, Sofar