A mixture of eight probiotic bacterial strains only somewhat outperformed placebo for preventing endoscopic recurrence after ileal resection in Crohn’s disease patients, according to a multicenter, randomized trial.
After 90 days of treatment, 9.3% of patients who received the probiotic mixture (VSL#3) had developed severe endoscopic recurrence, compared with 15.7% of the placebo group (P = .19), reported Dr. Richard Fedorak of the University of Alberta, Edmonton, and his associates.
The recurrence rate for the placebo group was about two-thirds lower than what the researchers had expected based on the sample size calculation, they noted. But the probiotic blend was linked to significantly significant decreases in colonic mucosal levels of proinflammatory cytokines, they reported (Clin. Gastroenterol. Hepatol. 2014 Nov. 6 [doi:10.1016/j.cgh.2014.10.031]).
Investigators have tested probiotics as a preventive therapy for Crohn’s disease because patients with active disease have less diverse intestinal microbiota, compared with those with quiescent disease or healthy controls. Past studies of single-strain probiotics have shown them to be no better than placebo for preventing endoscopic recurrence.
But in one small study, rifampin followed by VSL#3 outperformed mesalamine at 1 year (Gastroenterology 2000;118:A781), the researchers noted. “This mixture could confer protective effects where single-strain or lactobacillus-only formulations had failed,” they hypothesized.
To test that theory, the investigators randomized 120 patients with Crohn’s disease who had undergone ileal resection and ileocolonic anastomosis to twice-daily VSL#3 or placebo. Treatment began within 30 days after surgery and continued for 90 days, after which all patients received open-label VSL#3 for another 9 months.
Among patients who had nonsevere endoscopic lesions at day 90, 1-year rates of severe endoscopic recurrence were 10% for the early VSL#3 group, compared with 26.7% for the late VSL#3 group (P = .09), said the researchers. Likewise, combined rates of severe recurrence on days 90 and 365 were not statistically different, they reported. However, the early VSL#3 group had lower mucosal levels of 13 pro-inflammatory cytokines, compared with patients who received placebo until day 90 (P < .05). Measures of Crohn’s disease activity and disease-related quality of life scores were similar for both groups.
“Early treatment with VSL#3 had a larger effect than late treatment,” concluded the investigators. “Future larger studies will be needed to confirm the effect of VSL#3 in prevention of postoperative recurrence.”
The study was funded by VSL Pharmaceuticals, the Canadian Institutes of Health Research, and Crohn’s and Colitis Foundation of Canada. Dr. Fedorak reported having served on a speakers bureau for VSL Pharmaceuticals. The other authors declared no relevant conflicts of interest.