Table 3.

Clinical studies comparing efficacy between two enteral nutrition regimens. PCDAI = Pediatric Crohn’s Disease Activity Index, PF = polymeric formula, ED = elemental diet, PEN = partial enteral nutrition, 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 Efficacy between Two Enteral Nutrition Regimens
Author/Year	Study Type	Population	Method	Main Findings
Akobeng et al. 2000 [32]	Randomized controlled trial	Children with active CD (n = 18).	Standard PF with a low glutamine content (4% of amino-acid composition, group S) vs. glutamine enriched PF (42% of amino acid composition, group G) for 4 weeks.	- No difference in remission rates at week 4 between the two groups’ remission 5/9 (55.5%) in group S, 4/9 (44.4%) in group G (p = 0.5). ARC −0.11 (exact 95% CI: −0.57 to 0.35). - Improvement in mean PCDAI was significantly more in group S (p = 0.002).
Ludvigsson et al. 2004 [33]	Randomized controlled trial	Children with active CD (n = 33) involving small bowel, colon and perianal region.	Exclusive EEN with ED (n = 16) vs. PF (n = 17) for 6 weeks.	- Similar remission rates at 6 weeks (ED 11/16 (69%), PF 14/17 (82%); p = 0.438). Patients on PF gained more weight compared to ED (p = 0.004). ARC 0.14 (exact 95% CI: −0.15 to 0.42).
Johnson et al. 2006 [34]	Randomized controlled trial	Children with active CD (n = 50) involving small bowel and/or colon.	Patients randomly assigned to receive: - 50% total energy requirements with ED (PEN, n = 26) for 6 weeks. - 100% energy requirements with ED (EEN, n = 24) for 6 weeks.	Remission rate with PEN was lower than with EEN (PEN 4/26 (15%), EEN 10/24 (42%) p = 0.035). Although PCDAI fell in both groups, the reduction was greater with EEN (PCDAI reduction PEN −13, 95% CI (−7 to −19) p = 0.001; EEN −26 95% CI (−19 to −33), p = 0.001) (p = 0.005). ARC = −0.26 (exact 95% CI −0.50 to −0.02).
Rodrigues et al. 2007 [35]	Retrospective cohort study	Children with active CD (n = 98) involving small bowel and/or colon.	Children received EEN at the time of first presentation either PF (n = 45, median age 12.2 years) or ED (n = 53, median age 11.8 years).	Remission rates were similar between children receiving PF and ED (ED 64%, 95% CI 51–77 vs. PF 51%, 95% CI 37–66, p = 0.19). ARC = −0.13 (exact 95% CI −0.32 to 0.06). The use of PF did not affect adherence to EEN but was significantly associated with reduced need for nasogastric tube administration.
Hartman et al. 2008 [36]	Retrospective cohort study	Children with CD (n = 64) involving small bowel, colon and upper GI tract.	Group 1 (n = 28, median age 14 years) and group 2 (n = 18, median age 12.7 years) received TGFβ2-enriched PF vs. standard PF, respectively, as a supplement to their regular nutrition (35%–50% of total caloric intake), for a median follow-up of 5.3 months for group 1 and 4.5 months for group 2. Group 3 (n = 18, median age 12.8 years) without formula supplementation, for a median follow-up of 5.5 months.	Supplementation of the diet with PF (both TGFβ enriched and standard) was associated with a decrease in PCDAI (in group 1 from 34.3 to 15.7, p < 0.0001; in group 2 from 35 to 22, p = 0.02). No significant decrease in PCDAI was recorded in group 3. Remission rates at follow-up: 57% (16/28, p = 0.001) in TGFβ2-enriched PF group, 22.2% (4/18, p = 0.03) in standard PF group. Remission rate in group 3 was 22.2 (4/18, p = 0.03). ARC = 0.35 (exact 95% CI 0.08 to 0.61). Significant improvements in body mass index (p = 0.01) and erythrocyte sedimentation rate (p = 0.03) were recorded at follow-up (median 3.4 months) only in the TGFβ2-enriched PF group.
Rubio et al. 2011 [37]	Retrospective cohort study	Children with newly diagnosed CD or with a first relapse of an established disease on stable medical treatment (n = 106).	Children received EEN with PF for 8 weeks as remission induction therapy either per os (group 1, n = 45, mean age 11.3 years) or by continuous enteral route via a nasogastric tube (group 2, n = 61, mean age 10.9 years).	Fractionated oral nutritional therapy (group 1) didn’t significantly differ from continuous enteral administration (group 2) in inducing remission (75% vs. 85%, respectively, p = 0.157). All patients showed a significant decrease in disease severity assessed by PCDAI (p < 0.0001) and significant improvements in anthropometric measures and inflammatory indices.
Grogan et al. 2012 [38]	Double-blind randomized controlled trial	Children with newly diagnosed CD (n = 34).	Children were randomized to ED (n = 15, mean age 12.6 years) or PF (n = 19, mean age 11.7 years) for 6 weeks and were followed up for 2 years.	No significant difference was recorded between ED and PF in inducing remission (93% 14/15 vs. 79% 15/19, respectively). ARC = 0.14 (exact 95% CI −0.08 to 0.37). One-third of children maintained remission at 2 years.
Lee et al. 2015 [39]	Prospective study	Children with active CD (n = 90).	Children were treated with anti-TNF (n = 52), with EEN (n = 22), and with PEN plus ad lib diet (n = 16) for 8 weeks.	Clinical remission (final PCDAI ≤ 10) was achieved by 50% on PEN, 76% EEN, and 73% anti-TNF (p = 0.08). ARC= −0.15 (exact 95% CI −0.47 to −0.16). Mucosal healing (estimated by fecal calprotectin ≤ 250 μg/g) was achieved with PEN in 14%, EEN 45%, and anti-TNF 62% (p = 0.001). ARC = −0.25 (exact 95% CI −0.52 to 0.02).