Enteral nutritional therapy for inducing remission of Crohn's disease

The role of enteral nutrition in Crohn's disease is controversial. Increasing research on the mechanisms by which nutritional therapy improves the clinical well being of patients with Crohn's disease has led to novel formula design and trials comparing two different forms of enteral nutrition. This systematic review aims to provide an update on the existing efficacy data for both corticosteroids versus enteral nutrition and for one form of enteral nutrition versus another for inducing remission of active Crohn's disease.

To evaluate the efficacy of exclusive enteral nutrition as primary therapy to induce remission in Crohn's disease and to examine the importance of formula composition on efficacy.

Studies were selected using a computer-assisted search of the on-line bibliographic databases MEDLINE (1966-2000) and EMBASE (1984-2000), as well as the Science Citation Index on Web of Science. Additional citations were sought by manual search of references of articles retrieved from the computerized search, abstracts submitted to major gastroenterologic meetings and published in the journals: Gut, Gastroenterology, Journal of Pediatric Gastroenterology and Nutrition, and Journal of Parenteral and Enteral Nutrition, and from the reviewers' personal files or contact with leaders in the field.

All randomized and quasi-randomized controlled trials involving patients with active Crohn's disease defined by a clinical disease activity index were considered for review. Studies evaluating the administration of one type of enteral nutrition to one group of patients and another type of enteral nutrition or conventional corticosteroids to the other group were selected for review.

Data were extracted independently by two reviewers and any discrepancies were resolved by rereading and discussion. For the dichotomous variable, achievement of remission, individual and pooled trial statistics were calculated as odds ratios (OR) with 95% confidence intervals (CI); both fixed and random effect models were used. The results for each analysis were tested for heterogeneity using the chi square statistic. The studies were separated into two groups: A. one form of enteral nutrition compared with another form of enteral nutrition and B. one form of enteral nutrition compared with corticosteroids. Subgroup analyses were conducted on the basis of clinical or disease criteria and formula composition. Sensitivity analyses were conducted on the basis of the inclusion of abstracts of studies not yet fully published, methodologic quality and by random or fixed effects models.

In part A, of the 11 trials (one abstract) comparing different formulations of enteral nutrition ten compared one [or more (Middleton (a)1995)] elemental formulas to a non-elemental diet. The eleventh study (Akobeng 2000) compared two non-elemental diets differing only by glutamine enrichment in one group. This study was therefore not included in the primary analysis but was part of the subgroup analyses. Meta-analysis of nine studies which included 170 patients treated with an elemental diet and 128 patients treated with a non-elemental diet for active Crohn's disease demonstrated no significant difference among diet formulations [OR 1.15 (95% CI: 0.64, 2.08)]. Significant heterogeneity was not present [chi-square 9.77 (df=8)]. Subgroup and sensitivity analyses had no significant effect on the results. In part B, six trials (two abstracts) comparing enteral nutrition to steroid therapy met the inclusion criteria for review. Meta-analysis of four trials that included 130 patients treated with enteral nutrition and 123 treated with steroids yielded a pooled OR of 0.30 favouring steroid therapy (95% CI: 0.17, 0.52). Heterogeneity was not demonstrated [chi-square 0.43 (df=3)]. The risk difference calculated from this meta-analysis was 0.26, and the NNT (number of patients needed to treat with steroids rather than enteral nutrition to achieve one remission) was four. The same result was found in a sensitivity analysis that included abstracts. The inclusion of abstracts resulted in an increase in the number of participants to 150 in the enteral nutrition group and 142 in the steroid group but the meta-analysis yielded a similar result [OR 0.34 (95% CI: 0.20, 0.56)]. There were inadequate data from full publications to perform further subgroup analyses by age, disease duration and disease location.

Corticosteroid therapy is more effective than enteral nutrition for inducing remission of active Crohn's disease as was found in past meta-analyses. There is no significant difference in the efficacy of elemental and non-elemental diets for induction of remission of Crohn's disease.