Enteral nutrition versus immunomodulators for induction and maintenance of remission in pediatric Crohn's disease: a systematic review and network meta-analysis

Background: Enteral nutrition (EN) and immunomodulators are established therapies for pediatric Crohn's disease (CD), yet comparative effectiveness data remain limited. Objective: We conducted a network meta-analysis (NMA) to compare the efficacy and safety of EN therapies vs. immunomodulators and corticosteroids for remission induction and maintenance in pediatric CD. Methods: We systematically searched PubMed, Embase, Cochrane CENTRAL, and Web of Science from inception through October 2024. Randomized controlled trials (RCTs) and comparative observational studies evaluating exclusive enteral nutrition (EEN), partial enteral nutrition (PEN), Crohn's Disease Exclusion Diet plus PEN (CDED + PEN), supplemental enteral nutrition (SEN), corticosteroids (CS), azathioprine/6-mercaptopurine (AZA/6-MP), or methotrexate (MTX) were included. Primary outcomes were clinical remission and mucosal healing. Frequentist NMA was performed using random-effects models. Surface under the cumulative ranking curve (SUCRA) values determined treatment rankings. Results: = 0%]. EEN demonstrated marked superiority for mucosal healing vs. CS (OR 7.55; 95% CI 3.59-15.88). SUCRA rankings for remission induction were: CDED + PEN (0.80), EEN (0.78), MTX (0.55), AZA/6-MP (0.47), CS (0.31), and PEN (0.08). For maintenance, AZA/6-MP was superior to placebo (OR 12.50; 95% CI 2.47-63.14). EN therapies exhibited favorable safety profiles with serious adverse event rates of 0%-3.1% compared with 15.1% for CS and 11.8% for AZA/6-MP. Conclusions: EEN and CDED + PEN are the most effective treatments for inducing clinical and endoscopic remission in pediatric CD, with superior safety profiles compared to pharmacological therapies. Immunomodulators remain essential for maintenance therapy. These findings support EN as first-line induction therapy in pediatric CD. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261345561, PROSPERO CRD420261345561.