Clinical Question: In patients with ulcerative colitis currently in remission, is the probiotic Escherichia coli Nissle 1917 as effective as standard treatment to prevent relapse?
Setting: Outpatient (any)
Study Design: Randomized controlled trial (double-blinded)
Synopsis: Probiotics are live, nonpathogenic microorganisms used to alter the microbial balance in the intestinal tract. Although most probiotics are gram-positive species (e.g., Lactobacillus species),E. coli Nissle 1917 is a gram-negative probiotic of a different strain than toxic E. coli that may work by causing an immune response or preventing invasion of other bacteria.
In this trial, the investigators enrolled 327 patients with ulcerative colitis in remission who had a history of at least two acute attacks. Patients were assigned to receive E. coli Nissle 1917 probiotic in a dosage of 200 mg once daily or controlled-release mesalamine (called mesalazine everywhere but in the United States) three times daily for 12 months. The patients were examined once a month for three months, then every three months for the remainder of the study.
The investigators incorrectly entered or failed to follow up with 32 percent of the patients. Dropouts were common; by the end of the study, 50 percent of patients receiving E. coli Nissle 1917 and 43 percent of patients receiving mesalamine had discontinued therapy because of various problems or protocol violations. The authors did not mention whether additional therapy could be used or how acute relapse was managed, although they prohibited patients from using antibiotics, sulfonamides, or steroids at entry to the study.
The main outcome was the number of patients experiencing a relapse during the 12 months of the study, as measured by an undescribed clinical activity index. In patients who maintained therapy (per-protocol analysis), 36.4 percent of the patients in the E. coli Nissle 1917 group relapsed compared with 33.9 percent of patients receiving mesalamine. Relapse rates were similar between the groups when using intention-to-treat analysis (45.1 versus 37.0 percent). Discontinuation rates because of adverse effects were similar in the two groups. The study had a power of 20 percent to find at least a 20 percent difference (not a 20 percentage-point difference) in the rate of relapse, if one exists.
Bottom Line: Treating ulcerative colitis with the probiotic E. coli Nissle 1917 is as effective as prophylactic mesalamine in the prevention of relapse. No commercially available products containing this nonpathogenic bacteria were located, and the strain (Nissle 1917) is crucial. (Level of Evidence: 1b–)