Research Progress on Exclusive Enteral Nutrition Combined with Biologics in the Treatment of Adult Crohn’s Disease

Abstract Objective To critically evaluate the evidence and mechanistic basis for combining exclusive enteral nutrition (EEN) with biologics in adults with Crohn’s disease (CD), addressing the gap between strong theory and limited clinical proof. Methods We conducted a literature review up to May 2025, focusing on studies combining EEN with biologics (anti-TNF agents, vedolizumab, or Ustekinumab). We assessed methodological quality and bias. Results The current literature—mainly small, retrospective cohort studies—indicates that adding EEN to biologic therapy may increase clinical and endoscopic remission rates by 30–50% compared to biologic monotherapy. This effect is believed to be attributed to enhanced mucosal healing, alterations in the microbiome, and improved pharmacokinetics. However, these findings are based on studies with significant limitations, including selection bias, varying protocols, and lack of blinding. Conclusion Combined therapy with Exclusive Enteral Nutrition (EEN) and biologics shows promise in managing complex Crohn’s Disease (CD), with studies reporting improved remission rates. This clinical benefit may be attributed to a synergistic effect supported by a plausible biological basis. However, these favorable outcomes are based on low-certainty evidence from limited clinical studies. Robust randomized controlled trials are needed to establish the effectiveness, safety, and best use of this combination approach. Keywords: Crohn’s disease; Exclusive enteral nutrition; Combination therapy; Biologics; Mucosal healing