What is Crohn's disease?
Crohn's disease is a long-term inflammation of the gastrointestinal (GI) tract, occurring anywhere from mouth to anus. Common symptoms of this condition include abdominal pain, diarrhea and weight loss. When Crohn's disease patients are experiencing symptoms, it is characterized to be 'active' disease. When the symptoms stop, it is called 'remission'.
What is enteral nutrition?
Enteral nutrition is a feeding method where all of a person's daily caloric intake is delivered using the GI tract. An example of this is nasogastric tube feeding, where a tube is inserted through a person's nose to deliver their daily nutritional requirements in liquid form. Enteral nutrition can be a form of nutritional therapy for Crohn's disease patients. Enteral nutrition is categorized into elemental and non-elemental (semi-elemental and polymeric) diets. Elemental diets come from amino-acid sources, whereas non-elemental diets come from oligopeptide or whole protein sources.
What are corticosteroids?
Corticosteroids are an effective treatment option for active Crohn's disease. These drugs that are taken by mouth and work as immunosuppressants.
What did the researchers investigate?
The researchers studied whether enteral nutrition is better than steroid therapy at producing remission in Crohn's disease patients. In addition, the investigators looked to see if one type of enteral nutrition was better than another (e.g. elemental vs.non-elemental) at producing remission in Crohn's disease.
What did the researchers find?
The researchers found twenty-seven studies (1,011 participants) that fulfilled the search criteria. Eleven of these studies, which included 378 patients, compared elemental to non-elemental diets at producing remission in Crohn's disease. Eight studies, which included 352 patients, investigated enteral nutrition compared to steroid therapy at inducing remission in Crohn's disease. The researchers searched the medical literature extensively up to July 5, 2017.
Very low quality evidence suggests that steroids may be more effective than enteral nutrition for induction of remission in adults with active Crohn's disease. Very low quality evidence also suggests that enteral nutrition may be more effective than steroids for induction of remission in children with active Crohn's disease. There was no difference in remission rates between elemental and non-elemental diets. An increase in side effects was not seen with elemental diets compared to non-elemental diets, nor with enteral nutrition compared to steroids. Common side effects experienced with enteral nutrition included vomiting, diarrhea, heartburn and flatulence . Common side effects associated with steroid use included acne, moon facies, muscle weakness, hyperglycemia (high blood sugar) and hypoglycemia (low blood sugar) . Patients on enteral nutrition were more likely to withdraw from the study due to side effects than those on steroids. The most common reason for study withdrawal was inability to tolerate the taste of the enteral nutrition diet. Enteral nutrition should be considered in pediatric Crohn's patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided. Further research is required to confirm the superiority of corticosteroids over EN in adults. Further research is required to confirm the benefit of EN in children. More effort from industry should be taken to develop palatable polymeric formulations that can be delivered without use of a nasogastric tube as this may lead to increased patient compliance with this therapy.
Very low quality evidence suggests that corticosteroid therapy may be more effective than EN for induction of clinical remission in adults with active CD. Very low quality evidence also suggests that EN may be more effective than steroids for induction of remission in children with active CD. Protein composition does not appear to influence the effectiveness of EN for the treatment of active CD. EN should be considered in pediatric CD patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided. Further research is required to confirm the superiority of corticosteroids over EN in adults. Further research is required to confirm the benefit of EN in children. More effort from industry should be taken to develop palatable polymeric formulations that can be delivered without use of a nasogastric tube as this may lead to increased patient adherence with this therapy
Corticosteroids are often preferred over enteral nutrition (EN) as induction therapy for Crohn's disease (CD). Prior meta-analyses suggest that corticosteroids are superior to EN for induction of remission in CD. Treatment failures in EN trials are often due to poor compliance, with dropouts frequently due to poor acceptance of a nasogastric tube and unpalatable formulations. This systematic review is an update of a previously published Cochrane review.
To evaluate the effectiveness and safety of exclusive EN as primary therapy to induce remission in CD and to examine the importance of formula composition on effectiveness.
We searched MEDLINE, Embase and CENTRAL from inception to 5 July 2017. We also searched references of retrieved articles and conference abstracts.
Randomized controlled trials involving patients with active CD were considered for inclusion. Studies comparing one type of EN to another type of EN or conventional corticosteroids were selected for review.
Data were extracted independently by at least two authors. The primary outcome was clinical remission. Secondary outcomes included adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes, we calculated the risk ratio (RR) and 95% confidence interval (CI). A random-effects model was used to pool data. We performed intention-to-treat and per-protocol analyses for the primary outcome. Heterogeneity was explored using the Chi2 and I2 statistics. The studies were separated into two comparisons: one EN formulation compared to another EN formulation and EN compared to corticosteroids. Subgroup analyses were based on formula composition and age. Sensitivity analyses included abstract publications and poor quality studies. We used the Cochrane risk of bias tool to assess study quality. We used the GRADE criteria to assess the overall quality of the evidence supporting the primary outcome and selected secondary outcomes.
Twenty-seven studies (1,011 participants) were included. Three studies were rated as low risk of bias. Seven studies were rated as high risk of bias and 17 were rated as unclear risk of bias due to insufficient information. Seventeen trials compared different formulations of EN, 13 studies compared one or more elemental formulas to a non-elemental formula, three studies compared EN diets of similar protein composition but different fat composition, and one study compared non-elemental diets differing in glutamine enrichment. Meta-analysis of 11 trials (378 participants) demonstrated no difference in remission rates. Sixty-four per cent (134/210) of patients in the elemental group achieved remission compared to 62% (105/168) of patients in the non-elemental group (RR 1.02, 95% CI 0.88 to 1.18; GRADE very low quality). A per-protocol analysis (346 participants) produced similar results (RR 1.04, 95% CI 0.91 to 1.18). Subgroup analyses performed to evaluate the different types of elemental and non-elemental diets (elemental, semi-elemental and polymeric) showed no differences in remission rates. An analysis of 7 trials including 209 patients treated with EN formulas of differing fat content (low fat: < 20 g/1000 kCal versus high fat: > 20 g/1000 kCal) demonstrated no difference in remission rates (RR 1.03; 95% CI 0.85 to 1.26). Very low fat content (< 3 g/1000 kCal) and very low long chain triglycerides demonstrated higher remission rates than higher content EN formulas. There was no difference between elemental and non-elemental diets in adverse event rates (RR 1.00, 95% CI 0.63 to 1.60; GRADE very low quality), or withdrawals due to adverse events (RR 1.29, 95% CI 0.80 to 2.09; GRADE very low quality). Common adverse events included nausea, vomiting, diarrhea and bloating.
Ten trials compared EN to steroid therapy. Meta-analysis of eight trials (223 participants) demonstrated no difference in remission rates between EN and steroids. Fifty per cent (111/223) of patients in the EN group achieved remission compared to 72% (133/186) of patients in the steroid group (RR 0.77, 95% CI 0.58 to 1.03; GRADE very low quality). Subgroup analysis by age showed a difference in remission rates for adults but not for children. In adults 45% (87/194) of EN patients achieved remission compared to 73% (116/158) of steroid patients (RR 0.65, 95% CI 0.52 to 0.82; GRADE very low quality). In children, 83% (24/29) of EN patients achieved remission compared to 61% (17/28) of steroid patients (RR 1.35, 95% CI 0.92 to 1.97; GRADE very low quality). A per-protocol analysis produced similar results (RR 0.93, 95% CI 0.75 to 1.14). The per-protocol subgroup analysis showed a difference in remission rates for both adults (RR 0.82, 95% CI 0.70 to 0.95) and children (RR 1.43, 95% CI 1.03 to 1.97). There was no difference in adverse event rates (RR 1.39, 95% CI 0.62 to 3.11; GRADE very low quality). However, patients on EN were more likely to withdraw due to adverse events than those on steroid therapy (RR 2.95, 95% CI 1.02 to 8.48; GRADE very low quality). Common adverse events reported in the EN group included heartburn, flatulence, diarrhea and vomiting, and for steroid therapy acne, moon facies, hyperglycemia, muscle weakness and hypoglycemia. The most common reason for withdrawal was inability to tolerate the EN diet.