Abstract Background Upadacitinib, a selective JAK1 inhibitor, has demonstrated efficacy in clinical trials for moderate-to-severe ulcerative colitis (UC). However, real-world effectiveness data in treatment-experienced populations remain limited. This study evaluates the real-world effectiveness, safety, and impact of prior biologic treatment lines on upadacitinib response in UC patients managed in routine clinical practice. Methods Ambispective data collection from 120 UC patients initiating upadacitinib across 15 hospitals in Andalusia, Spain (UPITA-Colitis Registry). Clinical remission (CR) was defined as partial Mayo score 3. Clinical-biochemical remission (CBR) required partial Mayo score 3, CRP 5 mg/L, and fecal calprotectin 250 μg/g. Steroid-free remission (SFR) was assessed as Mayo score 3 without corticosteroids from week 8 onwards. Outcomes were evaluated at weeks 8, months 6 and 12, with stratification by number of prior biologic treatment lines. Results Mean age was 38.6 years (61.9% male) with extensive colitis in 53.3%, left-sided disease in 38.3. Mean disease duration was 9.1 years with mean 2.3 prior advanced therapies (median 2). Previous treatment data is shown in Table 1 an efectiveness data in Table 2. Stratification by prior biologic lines demonstrated a significant impact on clinical-biochemical remission at 12 months, with composite CBR of 57.1% in patients with 1 prior treatment line versus 18.8% in those with ≥2 prior lines (p = 0.035). Adverse events occurred in 26 instances across 21.7% of patients. The most common adverse event was acne (n = 13, 50.0% of all events), followed by herpes zoster reactivation (n = 5, 19.2%). Other adverse events included Clostridioides difficile infection (n = 2), urinary tract infections (n = 2), paresthesia (n = 1), mucocele (n = 1), hair loss (n = 1), and mild neutropenia (n = 1). Eight patients (6.7%) discontinued treatment due to adverse events, most commonly related to pneumonia (n = 2), herpes zoster (n = 2), and acne (n = 2), with one patient each discontinuing due to elevated transaminases and cutaneous lesions. Conclusion Upadacitinib demonstrates sustained real-world effectiveness and safety in treatment-refractory UC patients, including multirefractory individuals. Clinical remission rates exceed 70% from week 8 and are maintained through 6 and 12 months. Although superior outcomes are observed in patients with fewer prior biologic failures, clinically relevant remission rates are achieved even in multiply-refractory patients. The safety profile requires careful monitoring, with adverse events occurring in approximately 22% of patients. Upadacitinib represents a valuable therapeutic option for refractory ulcerative colitis in real-world clinical practice. Conflict of interest: Dr. Caballero Mateos, Antonio M: has received fees for lectures, consultancy work, or research support from: Lilly, Abbvie, Johnson & Johnson, Takeda, Pfizer, Alfasigma, Ferring, Farmasierra, Kern. Moreno Barrueco, Melody: None Valdes, Teresa: none Ruíz Sánchez, Alicia: None Rodriguez Gonzalez, Francisco Jose: None Hernandez Martinez, Alvaro: None Martin Rodríguez, María Del Mar: As a speaker or recipient of educational funding from MSD, Takeda, Janssen, Johnson & Johnson, Dr. Falk Pharma, Abbvie, Tillotts Pharma, Chiesi, Otsuka Pharmaceutical, Pfizer, Galápagos, Ferring and Lilly. Gomez Delgado, Elena: None Trapero Martinez, Ana María: None Benítez Cantero, José Manuel: None Mata Perdigón, Francisco Jesús: None Saldaña, Leticia: None Miras Lucas, Leticia Maria: None González García, Javier: None Sáez Díaz, Antonia: None Olmedo-martín, Raúl: Dr. Raúl Olmedo-Martín has served as a speaker and consultant for Janssen, Abvvie, Kern, Takeda, Lilly, Otsuka, Ferring and Alfasigma
Mateos et al. (Thu,) studied this question.