Probiotics for Maintenance of Remission in Ulcerative Colitis: A Cochrane Systematic Review

Abstract

Background: Ulcerative colitis (UC) is a chronic relapsing disease characterised by diffuse mucosal inflammation of 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. Five years ago, a Cochrane review found only 4 studies and no evidence regarding the efficacy of probiotics, but much work has been published in recent years. An up to date Cochrane systematic review was performed to determine the efficacy and safety of probiotics for the maintenance of remission in ulcerative colitis.

Methods: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and the Cochrane Inflammatory Bowel Disease Group Specialised Trial Register were searched (Inception-January 2015). Manufacturers of probiotics were contacted to identify any unpublished trials. References of trials were also searched for any additional trials. Abstracts were considered for inclusion if full details to judge inclusion and risk of bias were offered or available from the authors. 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 extraction and assessment of methodological quality of included studies were independently performed by 2 authors. The main outcome measure was the occurrence of clinical or endoscopic relapse.

Results: The search yielded 1006 results, with 34 papers screened in full. Seven studies (n = 887) met the inclusion criteria and were included in the review. Four trials compared probiotics to mesalazine and 3 trials compared probiotics with placebo. The studies ranged in length from 3 to 12 months. The risk of bias was low for randomisation and allocation concealment in one study and unclear in the others. One study was open label, the rest rated as low risk for blinding as double-blinded double dummy trials. The risk of bias was high in one study due to incomplete outcome data and 2 studies due to selective reporting, all the remaining studies low risk. There was no statistically significant difference between probiotics and placebo for maintenance of remission in UC, although there were just 2 small studies with 92 participants (Odds Ratio 0.56; 95% CI 0.22-1.40). Meta-analysis of 4 studies (n = 638) found no statistically significant difference between probiotics and mesalazine (OR 1.29; 95% CI 0.92-1.80). There was no statistically significant difference in the incidence of adverse events (OR 1.16; 95% CI 0.79-1.71).

Conclusions: There was no statistically significant difference between probiotics and placebo, although there were just 2 small studies in the pooled analysis at some risk of bias. There was no difference in efficacy found between probiotics and mesalazine on pooled analysis and no difference in adverse events. Further research is proposed to investigate the role of probiotics to maintain remission in UC.