Combined Biologics and Exclusive Enteral Nutrition Promote Early Transmural Healing and Improve Long‐Term Outcomes in Crohn's Disease: A Multicenter Retrospective Study

Transmural healing (TH), a comprehensive therapeutic target in Crohn's disease (CD), is associated with reduced long‐term complications. However, evidence on the role of exclusive enteral nutrition (EEN) in TH remains limited. This study aimed to evaluate the efficacy of biologics combined with 16‐week EEN in achieving early TH and improving clinical outcomes. This real‐world, multicenter retrospective study analyzed medical records of patients with moderate‐to‐severe CD from 2016 to 2024. Patients received either biologics with concomitant 16‐week EEN (BioEEN) or biologics alone (Bio). Clinical and endoscopic outcomes, including transmural healing, were assessed at week 16, year 1, and year 2. At baseline, demographic and clinical characteristics were comparable between the two groups. The BioEEN group demonstrated superior clinical response rates compared to the Bio group (95.1% vs. 70.6% at week 16; P < 0.001), with sustained benefits at week 52 (87.8% vs. 59.5%; P < 0.001). Subgroup analysis revealed higher endoscopic response, mucosal healing, and TH rates in both colorectal and ileal segments at weeks 16 and 52 in the BioEEN group. Additionally, the BioEEN group had significantly lower rates of surgery, escalated treatment, bowel damage progression, and disease relapse at 1 and 2 years. Regression analysis identified the 16‐week EEN as the sole protective factor for early transmural healing and improved long‐term outcomes. Combined treatment of biologics and 16‐week EEN promotes early transmural healing, thereby enhancing long‐term clinical outcomes in CD patients.