Probiotics for maintenance of remission in ulcerative colitis.

BACKGROUND: Ulcerative colitis is a chronic relapsing disease characterised by diffuse mucosal inflammation limited to the colon. Current maintenance treatments have multiple adverse events and an effective treatment with minimal adverse events is desired. Several studies have demonstrated the importance of intestinal flora in the pathogenesis of ulcerative colitis. It has been suggested that modifying the bacterial flora with probiotics may attenuate the inflammatory process and prevent relapses in ulcerative colitis.

OBJECTIVES: The primary objectives were to determine the efficacy and safety of probiotics for the maintenance of remission in ulcerative colitis.

SEARCH METHODS: The Cochrane Central Register of Controlled Tials (CENTRAL), MEDLINE (1966 to July 2011), EMBASE (1974 to July 2011), CINAHL (1982 to July 2011) and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialised Trial Register were searched. Manufacturers of probiotics were contacted to identify any unpublished trials. References of trials were also searched for any additional trials.

SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared probiotics against placebo or any other intervention for the maintenance of remission in ulcerative colitis were eligible for inclusion.

DATA COLLECTION AND ANALYSIS: Data extraction and assessment of methodological quality of included studies were independently performed by two authors. The main outcome measure was the occurrence of clinical or endoscopic relapse.

MAIN RESULTS: Four studies (n = 587) met the inclusion criteria and were included in the review. Three trials compared probiotics to mesalazine and one trial compared probiotics with placebo. The studies ranged in length from 3 to 12 months. The risk of bias was high in two studies due to incomplete outcome data and lack of blinding. The methods used for allocation concealment were unclear for all four studies. There was no statistically significant difference between probiotics and mesalazine for maintenance of remission in UC. Relapse was reported in 40.1% of patients in the probiotics group compared to 34.1% of patients in the mesalazine group (3 studies; 555 patients: OR 1.33; 95% CI 0.94 to 1.90 ; I(2) = 11%). There was no statistically significant difference in the incidence of adverse events. Twenty-six per cent of patients in the probiotics group experienced at least one adverse event compared to 24% of patients in the mesalazine group (2 studies; 430 patients OR 1.21; 95% CI 0.80 to 1.84; I(2) =27%). Adverse events reported in the mesalazine-controlled studies include diarrhea, mucous secretion, bloody stools, abdominal pain, flatulence and distension, nausea and vomiting and headache. A small placebo controlled trial (n = 32) found no statistically significant difference in efficacy. Seventy-five per cent of probiotic patients relapsed at one year compared to 92% of placebo patients (OR 0.27; 95% CI 0.03 to 2.68). Adverse events reported in the placebo-controlled study include flatulence, abdominal bloating and pain, changes in faecal consistency, arthralgia, sacroiliitis, tiredness, incontinence, stress, oral blisters, eye dryness, headache, dizziness, influenza, gastroenteritis, cystitis and pneumonia.

AUTHORS' CONCLUSIONS: Given the relatively small number of patients in the pooled analysis, the small number of events and the high risk and unclear risk of bias in the included studies, there is insufficient evidence to make conclusions about the efficacy of probiotics for maintenance of remission in UC. There is a lack of well-designed RCTs in this area and further research is needed.