Is Exclusive Enteral Nutrition an Effective Therapy for Adults With Crohn Disease?

Nurse filling a bottle of enteral nutrition, Palliative Care, Conceptual Image, horizontal composition
Although EEN remains the first-line induction treatment for children with Crohn disease, emerging research reveals favorable clinical outcomes for adults.

Due to symptoms such as nausea and loss of appetite, as well as other mechanisms, including gut dysbiosis and reduced intestinal absorption, malnutrition affects up to 75% of individuals with Crohn disease (CD).1 In addition, many patients are unable to achieve disease remission and satisfactory QOL with pharmacologic treatment alone. The result is a need for alternative and adjunctive therapies.2

Using Food as Therapy for Crohn Disease

Increasing evidence suggests that dietary interventions may have the potential to address both issues in CD. “Indeed, it is becoming clear that food components have the ability to modulate metabolic pathways, stimulate gene expression, and modify the microbiota composition,” along with providing required nutrients in individuals with CD, wrote Caio et al in a 2021 review.1

The effectiveness of dietary strategies in the management of CD in adults represents a growing topic of investigation. Most of the available evidence in this population has focused on exclusive enteral nutrition (EEN). EEN is considered the first-line induction treatment for CD in children, while corticosteroids are often used as first-line therapy in adult patients.3

Why EEN Remains First-Line Therapy in Children With Crohn Disease

“Meta-analyses have shown that EEN is effective for CD in adults, but not as effective as it is in children,” said Ashwin N. Ananthakrishnan, MD, MPH, associate professor of medicine at Harvard Medical School in Boston, director of the Crohn’s and Colitis Center at Massachusetts General Hospital (MGH) and physician investigator in the Clinical and Translational Epidemiology Unit at MGH. EEN is also less popular among adults for various reasons, such as the associated social restrictions, poor palatability, financial cost, and length of treatment.3

In a Cochrane review published in 2018, Narula et al conducted a meta-analysis of 8 trials with a combined total of 223 adults and children with CD and found no significant overall difference in remission rates with EEN compared with steroids.Subgroup analyses demonstrated lower remission rates for adults on EEN vs corticosteroids (45% vs 73%; risk ratio [RR], 0.65; 95% CI, 0.52-0.82), while there remained no significant difference between remission rates in children receiving EEN or corticosteroids (83% vs 61%; RR, 1.35; 95% CI, 0.92-1.97). 

These conclusions were based on evidence that the study authors deemed very low quality. The researchers noted that EEN may be indicated for certain adult patients, such as those in whom “steroid side effects are not tolerated or better avoided.”4

Favorable Outcomes in EEN for Adults With Crohn Disease

Although research on EEN in adults with CD remains limited, accumulating findings suggest EEN may play a valuable role in CD treatment. In a 2017 prospective study, Yang et al examined the effects of a 12-week EEN intervention in 41 adult patients with CD, including 10 with stenosis and 33 with intestinal fistula/abdominal abscess; the latter group also received antibiotics with or without percutaneous drainage. Following EEN, investigators observed full clinical remission in 80.5% of the total sample, as well as fistula closure in 75% of participants with entero-cutaneous fistula, resolution of abscess in 76% of patients, and mucosal healing in 47% of those with mucosal ulcers.5

A 2019 prospective, open-label study found a high rate of mucosal healing (79%) after a long-term course of oral EEN (mean time to response, 123 days) in a sample of 29 adults and children with CD (average age, 28.9±10.1 years) both in the active disease stage and in remission.6 This finding was superior to mucosal healing rates associated with both short-term EEN (33%-58%) and infliximab (22%-60%).

In a review published in 2021 in BMJ Open Gastroenterology, Mitrev et al stated that “EEN has superior rates of endoscopic healing than corticosteroids, a more objective treatment endpoint” than clinical remission. Various research has demonstrated relatively low rates of mucosal healing with corticosteroids, ranging from 0% to 29% across studies.7,3 “Mucosal healing improves long-term outcomes in CD beyond clinical remission alone, by reducing risk of clinical flares and need for surgery,” Mitrev et al noted.3

A 2018 prospective study of 32 adults with CD found reductions in disease activity (median Harvey-Bradshaw Index decreased from 5 points to 3 points; P =.003) and inflammatory markers such as C reactive protein (medium level decreased 10-5 mg/L; P =.005) after 2 weeks of EEN, with continued and similar improvements in participants continuing EEN and those who switched to partial EN for the remaining 6 weeks of the study.8

Multiple studies support the effectiveness of EEN in reducing postoperative complications in adult patients with CD, including a 2017 retrospective case-control study of 51 patients undergoing surgery for stricturing or penetrating complications.9 Outcomes were more favorable among those treated with EEN for at least 2 weeks before surgery, and 25% of these patients no longer needed surgery. Among those still requiring surgery, the length of surgery was shorter in EEN-treated patients compared with control participants, who showed a 9-fold increase [odds ratio, 9.1; 95% CI, 1.2-71.2; P =.04] in the incidence of postsurgical abscess and anastomotic leak compared with the EEN group.

“EEN has also been studied in combination with infliximab and [has] shown some efficacy in use in that setting,” Dr Ananthakrishnan added. A meta-analysis of 4 studies demonstrated significant improvement in rates of long-term remission in adults with CD who were treated with EEN combined with infliximab compared with those treated with infliximab alone (74.5% vs 49.2%; P <.01).3

Research Limitations on EEN in Adults

Despite the promising results observed thus far, much of the research on EEN in adults to date has had limitations, such as small sample size and low methodological quality. Additionally, it is not possible to conduct blinded studies of differences between enteral nutrition and a diet that includes whole foods.3 There is a need for large-scale, rigorously designed studies to further explore the efficacy of EEN in adults with CD.

Emerging research has shown promising results with other dietary approaches in this patient group, including the CD exclusion diet (CDED), which “aims to exclude dietary factors that have evidence for IBD onset or exacerbation,” and CDTREAT, a “whole food diet that aims to mimic the composition of EEN,” according to Mitrev et al.3

Dr Ananthakrishnan advises that clinicians “try dietary interventions in the right patient — milder disease, no high-risk features — and adopt the most evidence-based diet and have objective evidence of response using endoscopy and/or biochemical measurements such as fecal calprotectin.”

Several needs remain in this area, Dr Ananthakrishnan explained, including more knowledge of the “long-term benefit of dietary studies, more data on whether diets just improve symptoms or also resolve inflammation, and more research into the best diets and the mechanisms of action of dietary therapies” in adults with CD.

References

  1. Caio G, Lungaro L, Caputo F, et al. Nutritional treatment in Crohn’s diseaseNutrients. 2021;13(5):1628. doi:10.3390/nu13051628
  2. DuBois KE, Beets M, Blake C, McCabe J. P016 meta-analysis of dietary intervention effects in Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis. 2019;25(Suppl_1):S10. doi:10.1093/ibd/izy393.021
  3. Mitrev N, Huang H, Hannah B, Kariyawasam VC. Review of exclusive enteral therapy in adult Crohn’s disease. BMJ Open Gastroenterol. 2021;8(1):e000745. doi:10.1136/bmjgast-2021-000745
  4. Narula N, Dhillon A, Zhang D, Sherlock ME, Tondeur M, Zachos M. Enteral nutritional therapy for induction of remission in Crohn’s disease. Cochrane Database Syst Rev. 2018;4(4):CD000542. doi:10.1002/14651858.CD000542.pub3
  5. Yang Q, Gao X, Chen H, et al. Efficacy of exclusive enteral nutrition in complicated Crohn’s disease. Scand J Gastroenterol. 2017;52(9):995-1001. doi:10.1080/00365521.2017.1335770
  6. Chen JM, He LW, Yan T, et al. Oral exclusive enteral nutrition induces mucosal and transmural healing in patients with Crohn’s disease. Gastroenterol Rep (Oxf). 2019;7(3):176-184. doi:10.1093/gastro/goy050
  7. Atreya R, Neurath MF. Current and future targets for mucosal healing in inflammatory bowel disease. Visc Med. 2017;33(1):82-88. doi:10.1159/000458006
  8. Wall CL, Gearry RB, Day AS. Treatment of active Crohn’s disease with exclusive and partial enteral nutrition: A pilot study in adults. Inflamm Intest Dis. 2017;2(4):219-227. doi:10.1159/000489630
  9. Heerasing N, Thompson B, Hendy P, et al. Exclusive enteral nutrition provides an effective bridge to safer interval elective surgery for adults with Crohn’s disease. Aliment Pharmacol Ther. 2017;45(5):660-669. doi:10.1111/apt.13934