Table 4.

Clinical studies comparing exclusive enteral nutrition to corticosteroids. PCDAI = Pediatric Crohn’s Disease Activity Index, ED = elemental diet, PEN = partial enteral nutrition, CS = corticosteroids, EEN = exclusive enteral nutrition, IFX = infliximab, anti-TNF = anti-tumor necrosis factor, TGFβ2 = transforming growth factor beta 2, ARC = absolute risk change.

Clinical Studies Comparing Exclusive Enteral Nutrition to Corticosteroids
Author/Year	Study Type	Population	Method	Main Findings
Sanderson et al. 1987 [18]	Randomized controlled trial	Children and adolescents with active CD aged 8.6–17.2 years (n = 17) involving the small bowel.	- 8 children treated with CS - 9 children treated with exclusive ED via nasogastric tube	- Disease activity (Lloyd–Still activity index) of the children improved significantly in both ED and PF groups after 6 weeks (p < 0.01). Growth velocity improved more in the ED group
Thomas et al. 1993 [40]	Randomized controlled trial	Children with active CD (n = 24): - 8% (2/24) confined to the small bowel - 29% (7/24) had ileal ± caecal involvement - 25% (6/24) ileocolic disease - 38% (9/24) disease confined to the colon	Children randomized to receive ED (n = 12) or CS (n = 12) for 4 weeks.	- Similar improvement in disease activity (PCDAI) and remission duration in both groups regardless of site of disease. In CS group activity index at baseline: 74, at week 4: 85, median change +11, (p < 0.01); in ED group activity index at baseline: 77, at week 4: 88, median change +11 (p < 0.01). - Growth velocity significantly better in ED group compared to CS group.
Ruuska et al. 1994 [41]	Randomized controlled trial	Children with new onset or relapsing CD (n = 19). Ten children had widespread disease affecting both colon and small intestine; in three the disease was limited to the colon and rectum, and six children had only small bowel disease.	- 10 children treated with a whole-protein based formula through a nasogastric tube for 11 weeks -9 children received high dose CS for 11 weeks	- Similar improvements of PCDAI index, clinical symptoms and inflammatory markers within 2 weeks of treatment in both groups. After the end of the follow-up period 2 months after cessation of the treatment, PCDAI was still low in both groups (PCDAI 11.9 ± 7.9 in enteral diet group and 14.3 ± 9.6 in CS group) - During the routine follow-up after the trial (0.3–2.5 years, mean 1.3 years), five of the CS group 55.5% (5/9) whereas only one from the enteral group 10% (1/10) experienced a clinical relapse. ARC = −0.46 (exact 95% CI −0.8 to −0.08).
Terrin et al. 2002 [42]	Randomized controlled trial	Children with active CD (n = 20), aged 7–17 years, involving the terminal ileum and different areas of the colon; no fistulae or strictures were detected.	- Group A: CS and mesalazine (n = 10) - Group B: enteral nutrition group treated with extensively hydrolyzed formula for 8 weeks (n = 10)	- Clinical remission was achieved in 90% (9/10) of patients in group B but only in 50% (5/10) in corticosteroid group (p < 0.01). ARC = 0.40 (exact 95% CI 0.04 to 0.76). Both treatments were effective in reducing PCDAI scores (baseline group A 32.0 ± 4.7, group B 34.0 ± 4.3; at week 8 group A 13.0 ± 5.18, group B 7.2 ± 3.15, p < 0.01), endoscopic scores (baseline group A 3.7 ± 0.48, group B 3.8 ± 0.42; at week 8 group A 2.4 ± 0.96, group B 1.1 ± 0.87, p < 0.01) and histological scores (baseline group A 3.3 ± 0.67, group B 3.5 ± 0.52; at week 8 group A 2.5 ± 0.52, group B 1.3 ± 0.82, p < 0.05 for group A, p < 0.01 for group B). Group B had significantly lower post-trial PCDAI scores than the CS group (PCDAI scores change group B 14.6 ± 3.6, p < 0.01, group A 24.8 ± 4.4, not significant))
Borrelli et al. 2006 [43]	Randomized controlled trial	Children with active naïve CD (n = 37).	- 19 children received EEN with PF for 10 weeks - 18 children received oral CS for 10 weeks	At week 10 the remission rate was comparable between two groups: 15/19 (79%, 95% CI 56–92) in PF group and 12/18 (67%, 95% CI 44–84) in CS group (p = 0.4, not significant). ARC = 0.12 (exact 95% CI −0.16 to 0.40). The proportion of children showing mucosal healing was significantly higher in the PF (14/19, 74%; 95% CI 51 to 89) than the CS group (6/18, 33%; 95% CI 16 to 57; p < 0.05). ARC = 0.40, (exact 95% CI 0.11 to 0.70). At week 10 both endoscopic and histologic scores significantly decreased only in PF group. For endoscopic score: in PF group pre-trial 12.9 ± 0.8, post-trial 5.9 ± 0.5, p < 0.001, in CS group pre-trial 12.9 ± 0.9, post-trial 9.8 ± 1.3, not significant. For histologic scores: in PF group ileum score pre-trial 10.4 ± 0.4, post-trial 3.8 ± 0.5, p < 0.001, in CS group pre-trial 11.0 ± 04, post-trial 9.6 ± 0.7, not significant.
Berni Canani et al. 2006 [44]	Retrospective cohort study	Children with newly diagnosed CD (n = 47), mean age 12.1 years.	Children received nutritional therapy (NT) for 8 weeks as - Polymeric formula (n = 12) - Semi-elemental diet (n = 13) - Elemental diet (n = 12) Ten subjects received oral CS for 8 weeks.	Similar clinical remission rates were observed after 8 weeks of treatment: 86.5% (32/37) receiving NT vs. 90% (9/10) treated with CS. ARC = −0.04 (exact 95% CI −0.25 to 0.18). Improvement in mucosal inflammation occurred in 64.8% (26/37) of patients on NT and 40% (4/10) of children on CS (p < 0.05).
Soo et al. 2013 [45]	Retrospective cohort study	Children with newly diagnosed CD (n = 105).	Children received either EEN (n = 36, mean age 12.9 years) or corticosteroids (n = 69, mean age 11.2 years) as induce remission therapy	Remission rate similar in two groups 88.9% (32/36) in the EEN group vs. 91.3% (63/69) in the CS group (p = 0.73) at 3 months). ARC= −0.02 (exact 95% CI −0.15 to 0.10). Relapse rate (40.6% vs. 28.6%), similar in both treatment groups (p = 0.12) over 12 months).
Luo et al. 2015 [46]	Retrospective cohort study	Children with newly diagnosed mild to moderate CD.	Children received either EEN (n = 10; median age 11.6 years) or CS (n = 18; median age 11.1 years) for 8 weeks.	The remission rate in EEN group was significantly higher than that in CS group (90.0% vs. 50.0%, respectively, p < 0.05).
Grover et al. 2015 [47]	Retrospective analysis of records	Children with newly diagnosed CD (n = 89) involving ileal, ileocolonic, and colonic sites.	Children received either EEN (n = 43; median age 13 years) or CS (n = 46; median age 11.5 years) as remission induction therapy together with an early use of thiopurines (within 6 months from diagnosis) as maintenance therapy. They were followed up for at least 2 years.	Choice of EEN over CS induction was associated with reduced linear growth failure (7% vs. 26%, p = 0.02), CS dependency (7% vs. 43%, p = 0.002), and improved primary sustained response to IFX (86% vs. 68%, p = 0.02).