Editorial: is enteral nutrition back in acute severe ulcerative colitis?

Abstract

Acute severe ulcerative colitis (ASUC) is a life-threatening condition with a mortality rate of approximately 1%.1 Since the landmark study from Truelove and Witts, intravenous steroids remain the mainstay of treatment as recommended by the last update of the European Crohn s Colitis Organisation consensus.2 However, steroids provide only 60%-70% of response within a few days.3,4 During the last decades, many trials aiming to improve this response rate have failed. Adding antibiotics, bowel rest or parenteral nutrition to steroids, or using ciclosporin as first-line medical therapy, did not significantly improve the outcome of ASUC with conventional therapy. The recently published randomised controlled trial from Sahu et al showed that adding exclusive enteral nutrition (EEN) to intravenous steroids was more effective than steroids alone in ASUC.5 The authors conducted an open-label single-centre trial in New Delhi comparing semi-elemental EEN for 7 days to standard of care in adults admitted with ASUC. Due to the coronavirus pandemic, the study was prematurely halted, recruiting only 62 patients of the 120 initially planned. Sahu et al observed a 57% steroid response rate in patients from the non-intervention arm compared to a 75% rate in those who received EEN. The difference was nearly significant in intention-to-treat analysis (P = 0.051) but reached statistical significance on per-protocol analysis after excluding 16% of patients who discontinued enteral feeding (P = 0.04). This remarkable finding is hampered by several limitations. First, the primary endpoint was steroid failure defined by change to a second-line medical therapy or the need for colectomy. This purely subjective criterion based on medical decision is an important weakness of the trial, since it was conducted in one centre and not blinded. No reliable objective endpoint based on symptoms and/or biomarkers was used as primary endpoint. Moreover, it remains unclear if randomised patients were evaluated after receiving 3, 5 or 7 days of intravenous steroids. Second, assuming a 55% steroid response rate with standard of care, the statistical hypothesis was quite optimistic, expecting an increase of 25% with EEN. Indeed, achieving 80% of response with steroids in ASUC has never been observed in any controlled trials to date. Third, important anthropometric data concerning patients nutritional status at baseline are lacking. Albumin levels were low and similar in both groups, but this has poor specificity in ASUC. Last, as acknowledged by the authors, there is no rationale for using semi-elemental enteral nutrition instead of a polymeric one in ulcerative colitis (UC). This trial outlines the impact of nutritional support, and especially enteral feeding, in the management of patients with ASUC. As observed in a head-to-head trial conducted in UC, EEN has similar efficacy to parenteral nutrition and better safety.6 Controlled trials are now awaited to further confirm these findings and explore the possible benefits of partial enteral feeding in association with a specific dedicated diet for UC, similar to that developed for paediatric Crohn s disease.7