P1036One-Year Outcomes of Advanced Combination Therapy in Refractory Inflammatory Bowel Disease

Background Advanced combination therapy (ACT), using two biologics or a biologic plus a small molecule, aims to improve efficacy by targeting multiple inflammatory pathways. Although short-term results are encouraging, long-term data remain limited. This study evaluated one-year clinical and biological outcomes of ACT in refractory inflammatory bowel disease (IBD) Methods We conducted a prospective, single-centre observational study including adult patients with ulcerative colitis (UC) or Crohn’s disease (CD) who initiated ACT between March 2024 and September 2025. Clinical response was defined as a ≥ 3-point decrease in partial Mayo Score (pMS) or Harvey-Bradshaw Index (HBI) and clinical remission as pMS ≤2 or HBI ≤4. Biological response was defined as a ≥ 50% reduction in C-reactive protein (CRP) and faecal calprotectin (FC) values compared with baseline, and remission as CRP <5 mg/L together with FC < 250 µg/g. Assessments were performed at weeks 16, 32 and 52 Results A total of 28 patients were enrolled, 18 diagnosed with UC (64.3%) (Figure 1A). Most frequently used combination was vedolizumab (VEDO) plus upadacitinib (UPA) (Figure 1B). Clinical and biochemical parameters improved progressively from baseline to 52 weeks. Median pMS decreased from 7 [IQR 5–8] to 4 [3–5] at week 16, 2 [1–5] at week 32, and 0 [0–2] at week 52 (p < 0.001) (Figure 2A). HBI showed no sustained reduction, starting at 13 [7.5–16], dropping to 5 [3–13] at week 16 but rising to 12 [3.5–14.5] at week 32 and week 52, with no significant differences (p = 0.453) (Figure 2B). Faecal calprotectin decreased from 1927.5 µg/g [929.3-4160.3] to 757.5 [334.5-2491.8] at week 16, 897 [36.5-2059.8] at week 32, and 222 [80.5-3272.0] at week 52 (p = 0.002) (Figure 2C). CRP levels declined from 17.3 mg/L [3-66] to 3.5 [1.3-10.5] at week 16, 2 [1.0-12.8] at week 32, and 1.5 [1.0-6.8] at week 52 (p < 0.001) (Figure 2D). At week 16, 66% of patients achieved clinical response and 18% clinical remission; by week 52, clinical response remained stable at 62%, while clinical remission increased to 56%. Similarly, biological response and remission improved from 48% and 14% at week 16 to 68% and 62% at week 52 (Figures 2E-2F) The median duration on ACT was 14 months. Therapy was discontinued in 11 patients (8 due to improvement and 3 due to lack of efficacy). 7 patients required treatment intensification. Mild adverse events were recorded in 14 patients, none requiring treatment withdrawal Conclusion After 52 weeks, ACT achieved sustained clinical and biological improvement with a favourable safety profile in refractory IBD. The VEDO–UPA combination was most frequently used and associated with consistent remission. Larger prospective studies are required to validate these results Conflict of interest Ms. Rodríguez Gallardo, María: None Valdes Delgado, Teresa: No conflict of interest Gonzalez Parra, Ana Caridad: No conflict of interest Maldonado Pérez, María Bélen: No conflict of interest Mouhtar El Halabi, Samer Alejandro: None Belvis Jiménez, María Inmaculada: No conflict of interest Argüelles Arias, Federico: I have recivied research support or speaker bureau from AbbVie, Amgen, AstraZeneca, Celltrion, Ferring, Falk Pharma, Alfa Sigma, Janssen/J&J, Neopharm, Pfizer, MSD, Takeda, STADA Arzneimittel, Sandoz, Lilly