P0664 Effectiveness and safety of upadacitinib in ulcerative colitis in clinical practice: results from the U-REAL-UC study from ENEIDA
Authors: Chaparro M , Hermida S , Zabalza San Martín L , Tosca Cuquerella J , de Castro L , Larrubia Domínguez C , Rodríguez-Lago I , Reygosa Castro C , Varela Trastoy P , Gargallo-Puyuelo C J , Ripoll Abadía P , Ruiz-Cerulla A , Barreiro-de Acosta M , de Francisco R , Gutiérrez A , Jiménez N , Pajares Villarroya R , Bujanda L , Trapero Martínez A M , Arias García L , Camargo Camero R , Calafat M , Diz-Lois Palomares M T , Robledo Andrés P , Sampedro M J , Ber Nieto Y , Bermejo F , Calvo Moya M , Casanova M J , Ceballos D , Martín-Rodríguez D , Mesonero F , Zabana Y , Sanjosé Crespo A , Sierra-Ausín M , Caballol B , Curieses Luengo M , Giordano A , Domènech E , Gisbert J P 
Published: January 2025

Abstract

Background
Upadacitinib (UPA) has shown promising results in the pivotal trials, which require validation in clinical practice. Primary aim:To assess the durability of UPA treatment in patients with ulcerative colitis (UC). Secondary aims:To assess the short and long-term effectiveness, dose optimization and response to dosage adjustments, the impact of extraintestinal manifestations (EIM) and immunomediated diseases (IMIDs), and the tolerability of UPA in UC in a real-world setting

Methods
Adult patients who started UPA for UC treatment at least 8 weeks prior to data collection and were part of the prospectively maintained ENEIDA registry of GETECCU were included. Patients on concomitant biologic agents or with a history of colectomy were excluded. Patients were followed-up from the first UPA dose until treatment discontinuation or the last visit. Effectiveness analysis was restricted to patients with active disease [Partial Mayo Score (PMS)&gt;2] at UPA initiation. Clinical effectiveness was measured using PMS, and concomitant steroid use was assessed at each visit. Patients who discontinued UPA before their last visit were considered not in remission at subsequent time points (negative imputation)

Results
The study included 168 patients, 89% with active disease (Table 1); 48% had been previously exposed to JAK inhibitors (JAKi) and 31% to all approved therapeutic targets. Dosage details are summarized in Table 2. A total of 29 patients discontinued treatment during a median follow-up time of 4.3 months.The incidence rate of UPA discontinuation was 27% per patient-year of follow-up (Fig. 1), with no significant differences related to prior JAKi exposure (Fig. 2).The main reason for UPA discontinuation was loss of response (34%), with colectomy being the main subsequent treatment (21%). No predictive factors for UPA discontinuation were identified (Fig. 1). At week 8, 67% of patients were in steroid-free clinical remission (SFCR) (Fig. 3).Prior exposure to JAKi affected short-term effectiveness (Table 3). Among 100 patients in SFCR at week 8, 13 (13%) lost response (31% per patient-year), and 10 (77%) of these had dose escalation, with 4 (90%) regaining SFCR. Of 31 patients (18%) with active EIM/IMIDs at the start of UPA, 15 (48%) showed improvement.Adverse events occurred in 45 patients (27%) with hypercholesterolemia being the most common, but no major cardiovascular or thromboembolic events were reported

Conclusion
This study, the largest of its kind in clinical practice, confirms the short- and long-term benefits and the safety profile of UPA for UC. Although prior JAKi exposure reduced short-term effectiveness, it did not impact drug survival, indicating that UPA could be a viable option even for patients who have experienced JAKi failure