Ulcerative colitis—Maintanance of Remission With the Probiotic Escherichia coli Strain Nissle 1917

Abstract

We would like to comment on the American Gastroenterological Association Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders1Su G.L. et al.Gastroenterology. 2020; 159: 697-705Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar and the accompanying technical review2Preidis et al.Gastroenterology. 2020; 159: 708-738Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar published in Gastroenterology in August 2020. The guidelines also cover the probiotic Escherichia coli Nissle 1917 with respect to inflammatory bowel diseases. We agree with the conclusions that this specific probiotic plays no evidence-based role in the treatment of Crohn’s disease or in the induction of remission in ulcerative colitis. However, there is considerable evidence in favor of E coli Nissle with respect to maintenance treatment of ulcerative colitis. It is stated that “two studies of E coli Nissle 1917 and 1 study of L. rhamnosus ATCC 53103 (RR, 0.82; 95% CI, 0.60–1.11) did not show clear benefit of the probiotic compared to mesalamine for maintenance of remission.”1Su G.L. et al.Gastroenterology. 2020; 159: 697-705Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar Strictly correct, the statement missed the point of noninferiority studies—that is, showing equivalence of the probiotic to an established maintenance therapy in controlled trials head to head. It would also have been unethical to use a placebo control if an effective maintenance therapy is available. The same point is also made in the technical review,2Preidis et al.Gastroenterology. 2020; 159: 708-738Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar which in a confusing discussion mixes induction3Matthes H. et al.Altern Med. 2010; 10: 13Google Scholar,4Munk Petersen A. et al.J Crohn's Colitis. 2014; 8: 1498-1505Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar with maintenance studies.5Kruis W. et al.Aliment Pharmacol Ther. 1997; 11: 853-858Crossref PubMed Scopus (721) Google Scholar, 6Kruis W. et al.Gut. 2004; 53: 1617-1623Crossref PubMed Scopus (948) Google Scholar, 7Rembacken B.J. et al.Lancet. 1999; 354: 635-639Abstract Full Text Full Text PDF PubMed Scopus (997) Google Scholar Indeed, there are 4 studies on ulcerative colitis maintenance treatment that were covered in a more recent meta-analysis.8Losurdo G. et al.J Gastrointest Liver Dis. 2015; 24: 499-505Crossref PubMed Scopus (58) Google Scholar A total of 442 patients (223 with E coli Nissle and 219 with mesalamine) were included and the resulting odds ratio with 1.07 (95% confidence interval, 0.70–1.64) demonstrated equivalence. The dropout rate in one of the studies6Kruis W. et al.Gut. 2004; 53: 1617-1623Crossref PubMed Scopus (948) Google Scholar was not 46.5%, as stated in the technical review,2Preidis et al.Gastroenterology. 2020; 159: 708-738Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar but premature discontinuation occurred only in 11.9%; an overall per-protocol analysis could be performed in 222 of the 327 total study patients, or 67.9% of the intention-to-treat population.6Kruis W. et al.Gut. 2004; 53: 1617-1623Crossref PubMed Scopus (948) Google Scholar Thus, although any study may be criticized for various reasons, within the nonpharmacologic realm of probiotics the certainty of evidence for this specific E coli is as good as it gets. There also are multiple plausible mechanisms of action such as defensin induction.9Schlee M. et al.Infect Immun. 2007; 75: 2399-2407Crossref PubMed Scopus (248) Google Scholar Considering the multiple and sometimes critical side effects of mesalamine including renal impairment, pancreatitis, pleuritis, pericarditis and myocarditis,10Singh S. et al.Gastroenterology. 2019; 156: 769-808Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar E coli Nissle should be classified as an evidence-based and safe alternative. AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal DisordersGastroenterologyVol. 159Issue 2PreviewThis document presents the official recommendations of the American Gastroenterological Association (AGA) on the role of probiotics in the management of gastrointestinal disorders. The guideline was developed by the AGA Institute’s Clinical Guidelines Committee and approved by the AGA Governing Board. It is accompanied by a technical review that provides a detailed synthesis of the evidence from which these recommendations were formulated.1 To get a better understanding of these guidelines, we recommend reading the accompanying technical review. Full-Text PDF ReplyGastroenterologyVol. 160Issue 7PreviewWe are pleased to respond to letters from Stange et al and Koch et al regarding the American Gastroenterological Association (AGA) technical review and clinical practice guideline for the use of probiotics in the management of gastrointestinal disorders.1,2 Regarding the maintenance of remission in ulcerative colitis, Stange et al highlight a 2015 systematic review and meta-analysis that concluded probiotic Escherichia coli Nissle 1917 is equivalent to mesalamine.3 This conclusion is not dissimilar to ours; both meta-analyses suggest a trend toward either no benefit or modest benefit. Full-Text PDF