P0394Adalimumab versus Ustekinumab for reversing intestinal damage in Crohn’s disease

Abstract Background Crohn’s disease (CD) is a chronic progressive disorder characterized by transmural inflammation that can lead to structural bowel damage (SBD). Achieving transmural healing (TH) has emerged as a major therapeutic target in the biologic era. Intestinal ultrasound (IUS) provides a non-invasive tool to assess both inflammatory activity and structural complications. This study aimed to compare TH and clinical outcomes in CD patients treated with adalimumab or ustekinumab. Methods We performed a longitudinal observational study including CD patients,with different phenotypes, who initiated biological therapy between January 2020 and December 2023. Assessments were conducted at baseline, 12 weeks, and one year using IUS, Harvey–Bradshaw Index, C-reactive protein, and fecal calprotectin. TH was defined as bowel wall thickness ≤3 mm, absence of Doppler signal, and no complications. Outcomes included corticosteroid use, treatment intensification, hospitalization, and surgery. Statistical analyses were performed using Pearson’s Chi-squared or Fisher’s exact test (P 0.05). Results A total of 158 patients were included: adalimumab (n = 105, 65.2%) and ustekinumab (n = 53, 33.0%). Baseline SBD was similar between groups (adalimumab 67.2%, ustekinumab 31.2%; P = 0.617). At 12 weeks, TH was achieved in 18.6% overall, more frequently in non-SBD than in SBD (25.8% vs 7.8%respectively; P = 0.004). At one year, TH was present in 31.1% overall (non-SBD 34%, SBD 26.6%; P = 0.317). Adalimumab showed higher early TH rates (30.6% non-SBDvs 9.3% SBDat 12 weeks; P = 0.009), while ustekinumab demonstrated progressive TH improvement at one year in SBD patients (40% non-SBDvs 20.9%SBD; P = 0.045). Clinical outcomes, including corticosteroid use, hospitalizations, and surgeries, were similar between biologics. Conclusion Adalimumab induced faster transmural healing, particularly in inflammatory phenotypes, whereas ustekinumab showed progressive structural improvement over time in SBD patients. Both agents achieved TH in approximately one-third of patients after one year, suggesting that biologic therapy can promote reversal of structural bowel damage in Crohn’s disease. References: 1. Wilkens R, Novak KL, Maaser C, et al. Relevance of monitoring transmural disease activity in patients with Crohn’s disease: current status and future perspectives. TherapAdvGastroenterol. 2021. doi: 10.1177/17562848211006672. 2. Paredes JM, Moreno N, Latorre P, et al. Clinical Impact of Sonographic Transmural Healing After Anti-TNF Antibody Treatment in Patients with Crohn’s Disease. Dig Dis Sci. 2019;64:2600-2606. 3. Muñoz F, Ripollés T, Poza Cordón J, et al. Recommendations of the Spanish Working Group on Crohn’s Disease and Ulcerative Colitis (GETECCU) on the use of abdominal ultrasound in inflammatory bowel disease. GastroenterolHepatol. 2021;44:158-174. 4. Calabrese E, Rispo A, Zorzi F, et al. Ultrasonography Tight Control and Monitoring in Crohn’s Disease During Different Biological Therapies: A Multicenter Study. ClinGastroenterolHepatol. 2022;20:711-722. 5. Fraquelli M, Castiglione F, Calabrese E, et al. Impact of intestinal ultrasound on the management of patients with inflammatory bowel disease: how to apply scientific evidence to clinical practice. Dig Liver Dis. 2020;52:9-18. 6. Fiorino G, Bonifacio C, Allocca M, et al. Impact of therapies on bowel damage in Crohn’s disease. United European Gastroenterol J. 2020;8:410-417. Conflict of interest: Dr. Marques Garcia, Pilar: No conflict of interest Albert Palomares, Sara: No conflict of interest Blanc Garcia, Esther: No conflict of interest Gomez Abril, Segundo Angel: No conflict of interest Paredes Arquiola, Jose Maria: No conflict of interest