Therapeutic Efficacy of Exclusive Enteral Nutrition with Specific Polymeric Diet in Pediatric Crohn's Disease

Crohn's disease (CD) is a lifelong chronic inflammatory disease of the gastrointestinal tract. Compared with adult-onset CD, pediatric CD is particularly characterized by rapid progression and extensive intestinal involvement at diagnosis [1]. Additionally, as children are in the growth phase, it is important to provide sufficient nutrients and minimize adverse effects associated with various drugs for pediatric CD [2]. Corticosteroids (CSs) have long been used as a treatment for pediatric CD. However, to minimize adverse effects, exclusive enteral nutrition (EEN) is recommended as first-line treatment for the induction of remission in children with CD [3]. EEN has recently become the preferred choice for induction therapy in pediatric CD in Europe but is less preferred in North America [4, 5]. Previous studies have reported that the efficacy rate of EEN for the induction of remission is approximately 70% to 80% [6, 7, 8].

Two types of EEN for induction therapy are available: monomeric and polymeric diets. A monomeric diet is more expensive and has fewer flavors than a polymeric diet, but no difference in efficacy has been identified between these two diets [9]. Thus, under general circumstances, a polymeric diet is recommended for induction therapy. In a retrospective study, Soo et al. [10] showed the effectiveness of EEN (polymeric or semi-elemental) versus CSs for the induction of remission in pediatric CD patients. Although a polymeric diet tastes better and is less expensive than a monomeric diet, no study has reported the effectiveness of a polymeric diet in Korean pediatric CD patients [11, 12]. Moreover, the Korean government provides only a monomeric diet for induction therapy in pediatric CD patients.

The present study aimed to compare the effectiveness of two therapeutic regimens (EEN with a commercially available polymeric diet [Encover®; JW Pharmaceutical, Seoul, Korea] and CSs) for induction therapy by analyzing both clinical and laboratory variables in pediatric CD patients.

This study showed that the effects of EEN with a polymeric diet did not differ from those of CSs for the induction of remission in Korean pediatric CD patients. Clinical remission rates after 8 weeks of induction therapy were not significantly different between pediatric CD patients treated with CSs and EEN (65.6% vs. 78.9%, p=0.318). Our results suggest that EEN with a polymeric diet is as effective as CSs for the induction of remission in Korean pediatric CD patients.

The management strategy for pediatric CD is evolving. Managing pediatric CD does not simply involve the induction of remission but considers growth and pubertal development, and it is necessary to minimize adverse effects due to drugs and disease complications [16]. Thus, it is more difficult for physicians to provide a management plan for pediatric CD patients. Although the exact mechanism of EEN is unclear, it has been widely used in pediatric CD patients as an induction therapy because it is associated with few complications and is effective with respect to growth and pubertal development [17].

In 2014, the European Crohn's and Colitis Organisation (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) issued consensus guidelines that recommend EEN as first-line therapy for the induction of remission in children with active CD [3]. According to the ECCO/ESPGHAN guideline, the use of CSs should be avoided in children whenever possible owing to their adverse effects, while oral CSs for induction therapy can be an option when children with moderate to severe active luminal CD cannot adhere to EEN [3, 11]. Furthermore, previous studies have shown that CSs do not improve endoscopic and histologic inflammatory lesions despite their beneficial effect on clinical response [18, 19].

A previous study by Grover et al. [20] showed the efficacy of EEN for inducing clinical remission (84%), mucosal remission (58%), and transmural remission (21%) in pediatric CD. Furthermore, early good endoscopic response with EEN induction led to decreased relapse, hospitalization, need for anti-tumor necrosis factor therapy, and surgical resection at 1 year [20]. Several retrospective studies have suggested that EEN is not only capable of inducing clinical remission but also of improving bone metabolism, increasing muscle mass, and decreasing visceral fat [21, 22]. Therefore, with many such advantages, EEN has become the preferred induction therapy worldwide [23].

In a randomized controlled trial in 2006, Borrelli et al. [11] showed comparable clinical remission rates for EEN with a polymeric diet (79%) and CS therapy (67%). The present study obtained similar results, with a clinical remission rate of 78.9% and 65.6% for EEN and CSs, respectively. Day et al. [24], in a systemic review in 2008, showed that disease location can affect the efficacy of EEN. However, Buchanan et al. [25] indicated that disease phenotype does not affect clinical remission and suggested that EEN should be offered to all pediatric CD patients. Furthermore, Day et al. [26] reported that EEN can also be beneficial to children with perianal disease, whether alone or in combination with luminal disease. The association between disease location and treatment outcomes of EEN was not observed in our study.

Although several studies have suggested EEN with a polymeric diet as a first-line treatment for CD, our study is the first to show its effects in Korean children [3, 11, 27]. The findings of our study suggest that the same results could be obtained with EEN using a specific polymeric product regardless of ethnicity. Furthermore, because only the effect of EEN with a monomeric diet has been confirmed in Korean adolescents, the government has funded only the monomeric diet in children with CD in Korea [12]. As the effectiveness of EEN with a polymeric diet has been confirmed by this study, patients are expected to choose from a variety of EEN formulas to suit their taste. Additionally, because a polymeric diet is less expensive and tastes better than a monomeric diet, this may increase the success rate of EEN with a polymeric diet [12].

The present study has some limitations. First, it was not a prospective randomized controlled trial. Thus, there might have been a selection bias that could have affected the results. In this study, the CS group had a higher PCDAI score and ESR than the EEN group before induction. Patients with more severe disease activity may have received CSs for induction therapy, which may have resulted in the introduction of a selection bias. Second, colonoscopy findings or fecal calprotectin levels were not assessed. Mucosal healing has recently emerged as the optimal treatment target in CD management. Thus, endoscopic evaluation and treatment optimization are crucial in the current era of treat-to-target [28, 29]. Third, only short-term follow-up results were included. Moreover, we were unable to investigate the adverse events of both treatments owing to the retrospective character of this study and the short-term follow-up period. Fourth, due to the lack of information on the small bowel in some patients, analysis results according to disease location may not be accurate. Despite these limitations, our study, to our knowledge, is the first to evaluate the effectiveness of EEN with a polymeric diet for the induction of remission in Korean children with active CD.

In conclusion, EEN with an oral polymeric diet was not inferior to CSs for the induction of remission in Korean children with CD. Induction therapy with polymeric EEN should be considered as first-line treatment along with monomeric EEN in these patients, considering the well-known adverse events associated with CS treatment.