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Treatment with the nonpathogenic probiotic yeast Saccharomyces boulardii does not prevent relapse in Crohn’s disease.
The finding – which nevertheless does "not allow the exclusion of the potential therapeutic efficacy of probiotics" – comes from the third study to assess S. boulardii in Crohn’s, wrote Dr. Arnaud Bourreille and colleagues. The results are in the August issue of Clinical Gastroenterology and Hepatology.
In a yearlong, randomized, double-blind, placebo-controlled study, Dr. Bourreille, of the CHU de Nantes, France, and colleagues looked at 159 adult patients enrolled at 32 centers during the acute phase of Crohn’s disease.
Patients were treated for 4 weeks with corticosteroids, budesonide, and/or aminosalicylates, according to the preference of each investigator, until remission. They were then randomized to receive either oral S. boulardii at 1 g daily or a placebo until the end of the study at week 52 or earlier, in the case of relapse, with follow-up conducted every 12 weeks.
Relapse was defined as registering a Crohn’s disease activity index (CDAI) higher than 220 points on follow-up; registering a CDAI between 150 and 220 with an increase of at least 70 points over the baseline value; or requiring a surgical procedure or medical treatment specifically for CD.
The authors found that by 1 year, 80 patients had experienced relapse of Crohn’s: 38 in the S. boulardii group (47.5%) and 42 in the placebo group (52.5%), a nonsignificant difference (P less than .05).
The authors also found that the median time to relapse was not statistically different between groups, at 40.7 weeks for the treatment group (range, 2.6-56.0) and 39.0 weeks for patients taking placebo (range, 0.1-55.0) weeks (P = .78).
Indeed, the only finding that did reach statistical significance was among treatment group and smoking status, where nonsmokers given placebo had more relapses (72.0%) than did those treated with S. boulardii (34.5%; P = .016 for the difference between cohorts).
"However, in smokers and former smokers, the proportion of relapse was not significantly different," added the authors.
Looking at safety, Dr. Bourreille reported that just over half of patients in each group complained of adverse events, including diarrhea, arthralgia, constipation, and abdominal pain.
"One oral fungal infection occurred in one patient treated with S. boulardii," he added. "None of the drug-related AEs was serious."
Compliance was greater than 90% in both the treatment and placebo groups.
Dr. Bourreille conceded that the study was limited by the use of clinical relapse as an endpoint, versus relapse defined by endoscopic findings.
"Clinical recurrence was chosen as the primary endpoint because endoscopic evaluation was not deemed necessary for the surveillance of nonsevere CD," wrote the investigators. "Moreover, at the time the study was designed, the concept of mucosal healing was not considered to be as relevant as it now is."
They added, however, that biological parameters of inflammation "were measured at each visit to ensure that clinical recurrence was associated with objective inflammation."
Dr. Bourreille and several coauthors disclosed ties with multiple pharmaceutical companies, including Biocodex, the maker of S. boulardii. Two coauthors were Biocodex employees.
This article by Bourreille and colleagues provides some incremental insights into both probiotic therapy for Crohn’s disease and the prevention of postoperative recurrence.
With regard to probiotic therapy, to date, there has been one small trial of Escherichia coli Nissle 1917 for active Crohn’s disease that was negative, one small trial of Saccharomyces boulardii for maintenance of medically induced remission that showed a benefit, one small trial of Lactobacillus rhamnosus GG for medically induced remission that was negative, and two small trials of Lactobacillus johnsonii for prevention of postoperative recurrence that were negative.
The current trial of S. boulardii for prevention of postoperative recurrence is also negative. Taken in total, the existing randomized controlled trial data do not support treatment of Crohn’s disease with probiotic therapy using E. coli Nissle 1917, S. boulardii, L. rhamnosus GG, or L. johnsonii.
As for prevention of postoperative recurrence, randomized controlled trials have demonstrated minimal efficacy for mesalamine, no efficacy for ciprofloxacin, efficacy for the imidazole antibiotics metronidazole and ornidazole (but also treatment limiting toxicity), modest efficacy for azathioprine and 6-mercaptopurine, and marked efficacy for anti–tumor necrosis factor antibody therapy (but these data are limited by small sample size).
The current trial of probiotic with S. boulardii as well as previous trials with L. johnsonii did not demonstrate efficacy for prevention of postoperative recurrence, thus indicating that at present there is not a role for probiotics for this treatment indication. This study highlights the investigational nature of probiotic therapy for Crohn’s disease, and the need to investigate alternative treatment strategies to alter the microbial flora, such as fecal microbiota transplantation and personalized medicine probiotic cocktails that replace specific missing microbial flora in individual patients.
Dr. William J. Sandborn is professor of medicine and adjunct professor of surgery, chief of the division of gastroenterology, and director of the UCSD IBD Center, University of California San Diego and UC San Diego Health System. He had no relevant conflicts of interest.
This article by Bourreille and colleagues provides some incremental insights into both probiotic therapy for Crohn’s disease and the prevention of postoperative recurrence.
With regard to probiotic therapy, to date, there has been one small trial of Escherichia coli Nissle 1917 for active Crohn’s disease that was negative, one small trial of Saccharomyces boulardii for maintenance of medically induced remission that showed a benefit, one small trial of Lactobacillus rhamnosus GG for medically induced remission that was negative, and two small trials of Lactobacillus johnsonii for prevention of postoperative recurrence that were negative.
The current trial of S. boulardii for prevention of postoperative recurrence is also negative. Taken in total, the existing randomized controlled trial data do not support treatment of Crohn’s disease with probiotic therapy using E. coli Nissle 1917, S. boulardii, L. rhamnosus GG, or L. johnsonii.
As for prevention of postoperative recurrence, randomized controlled trials have demonstrated minimal efficacy for mesalamine, no efficacy for ciprofloxacin, efficacy for the imidazole antibiotics metronidazole and ornidazole (but also treatment limiting toxicity), modest efficacy for azathioprine and 6-mercaptopurine, and marked efficacy for anti–tumor necrosis factor antibody therapy (but these data are limited by small sample size).
The current trial of probiotic with S. boulardii as well as previous trials with L. johnsonii did not demonstrate efficacy for prevention of postoperative recurrence, thus indicating that at present there is not a role for probiotics for this treatment indication. This study highlights the investigational nature of probiotic therapy for Crohn’s disease, and the need to investigate alternative treatment strategies to alter the microbial flora, such as fecal microbiota transplantation and personalized medicine probiotic cocktails that replace specific missing microbial flora in individual patients.
Dr. William J. Sandborn is professor of medicine and adjunct professor of surgery, chief of the division of gastroenterology, and director of the UCSD IBD Center, University of California San Diego and UC San Diego Health System. He had no relevant conflicts of interest.
This article by Bourreille and colleagues provides some incremental insights into both probiotic therapy for Crohn’s disease and the prevention of postoperative recurrence.
With regard to probiotic therapy, to date, there has been one small trial of Escherichia coli Nissle 1917 for active Crohn’s disease that was negative, one small trial of Saccharomyces boulardii for maintenance of medically induced remission that showed a benefit, one small trial of Lactobacillus rhamnosus GG for medically induced remission that was negative, and two small trials of Lactobacillus johnsonii for prevention of postoperative recurrence that were negative.
The current trial of S. boulardii for prevention of postoperative recurrence is also negative. Taken in total, the existing randomized controlled trial data do not support treatment of Crohn’s disease with probiotic therapy using E. coli Nissle 1917, S. boulardii, L. rhamnosus GG, or L. johnsonii.
As for prevention of postoperative recurrence, randomized controlled trials have demonstrated minimal efficacy for mesalamine, no efficacy for ciprofloxacin, efficacy for the imidazole antibiotics metronidazole and ornidazole (but also treatment limiting toxicity), modest efficacy for azathioprine and 6-mercaptopurine, and marked efficacy for anti–tumor necrosis factor antibody therapy (but these data are limited by small sample size).
The current trial of probiotic with S. boulardii as well as previous trials with L. johnsonii did not demonstrate efficacy for prevention of postoperative recurrence, thus indicating that at present there is not a role for probiotics for this treatment indication. This study highlights the investigational nature of probiotic therapy for Crohn’s disease, and the need to investigate alternative treatment strategies to alter the microbial flora, such as fecal microbiota transplantation and personalized medicine probiotic cocktails that replace specific missing microbial flora in individual patients.
Dr. William J. Sandborn is professor of medicine and adjunct professor of surgery, chief of the division of gastroenterology, and director of the UCSD IBD Center, University of California San Diego and UC San Diego Health System. He had no relevant conflicts of interest.
Treatment with the nonpathogenic probiotic yeast Saccharomyces boulardii does not prevent relapse in Crohn’s disease.
The finding – which nevertheless does "not allow the exclusion of the potential therapeutic efficacy of probiotics" – comes from the third study to assess S. boulardii in Crohn’s, wrote Dr. Arnaud Bourreille and colleagues. The results are in the August issue of Clinical Gastroenterology and Hepatology.
In a yearlong, randomized, double-blind, placebo-controlled study, Dr. Bourreille, of the CHU de Nantes, France, and colleagues looked at 159 adult patients enrolled at 32 centers during the acute phase of Crohn’s disease.
Patients were treated for 4 weeks with corticosteroids, budesonide, and/or aminosalicylates, according to the preference of each investigator, until remission. They were then randomized to receive either oral S. boulardii at 1 g daily or a placebo until the end of the study at week 52 or earlier, in the case of relapse, with follow-up conducted every 12 weeks.
Relapse was defined as registering a Crohn’s disease activity index (CDAI) higher than 220 points on follow-up; registering a CDAI between 150 and 220 with an increase of at least 70 points over the baseline value; or requiring a surgical procedure or medical treatment specifically for CD.
The authors found that by 1 year, 80 patients had experienced relapse of Crohn’s: 38 in the S. boulardii group (47.5%) and 42 in the placebo group (52.5%), a nonsignificant difference (P less than .05).
The authors also found that the median time to relapse was not statistically different between groups, at 40.7 weeks for the treatment group (range, 2.6-56.0) and 39.0 weeks for patients taking placebo (range, 0.1-55.0) weeks (P = .78).
Indeed, the only finding that did reach statistical significance was among treatment group and smoking status, where nonsmokers given placebo had more relapses (72.0%) than did those treated with S. boulardii (34.5%; P = .016 for the difference between cohorts).
"However, in smokers and former smokers, the proportion of relapse was not significantly different," added the authors.
Looking at safety, Dr. Bourreille reported that just over half of patients in each group complained of adverse events, including diarrhea, arthralgia, constipation, and abdominal pain.
"One oral fungal infection occurred in one patient treated with S. boulardii," he added. "None of the drug-related AEs was serious."
Compliance was greater than 90% in both the treatment and placebo groups.
Dr. Bourreille conceded that the study was limited by the use of clinical relapse as an endpoint, versus relapse defined by endoscopic findings.
"Clinical recurrence was chosen as the primary endpoint because endoscopic evaluation was not deemed necessary for the surveillance of nonsevere CD," wrote the investigators. "Moreover, at the time the study was designed, the concept of mucosal healing was not considered to be as relevant as it now is."
They added, however, that biological parameters of inflammation "were measured at each visit to ensure that clinical recurrence was associated with objective inflammation."
Dr. Bourreille and several coauthors disclosed ties with multiple pharmaceutical companies, including Biocodex, the maker of S. boulardii. Two coauthors were Biocodex employees.
Treatment with the nonpathogenic probiotic yeast Saccharomyces boulardii does not prevent relapse in Crohn’s disease.
The finding – which nevertheless does "not allow the exclusion of the potential therapeutic efficacy of probiotics" – comes from the third study to assess S. boulardii in Crohn’s, wrote Dr. Arnaud Bourreille and colleagues. The results are in the August issue of Clinical Gastroenterology and Hepatology.
In a yearlong, randomized, double-blind, placebo-controlled study, Dr. Bourreille, of the CHU de Nantes, France, and colleagues looked at 159 adult patients enrolled at 32 centers during the acute phase of Crohn’s disease.
Patients were treated for 4 weeks with corticosteroids, budesonide, and/or aminosalicylates, according to the preference of each investigator, until remission. They were then randomized to receive either oral S. boulardii at 1 g daily or a placebo until the end of the study at week 52 or earlier, in the case of relapse, with follow-up conducted every 12 weeks.
Relapse was defined as registering a Crohn’s disease activity index (CDAI) higher than 220 points on follow-up; registering a CDAI between 150 and 220 with an increase of at least 70 points over the baseline value; or requiring a surgical procedure or medical treatment specifically for CD.
The authors found that by 1 year, 80 patients had experienced relapse of Crohn’s: 38 in the S. boulardii group (47.5%) and 42 in the placebo group (52.5%), a nonsignificant difference (P less than .05).
The authors also found that the median time to relapse was not statistically different between groups, at 40.7 weeks for the treatment group (range, 2.6-56.0) and 39.0 weeks for patients taking placebo (range, 0.1-55.0) weeks (P = .78).
Indeed, the only finding that did reach statistical significance was among treatment group and smoking status, where nonsmokers given placebo had more relapses (72.0%) than did those treated with S. boulardii (34.5%; P = .016 for the difference between cohorts).
"However, in smokers and former smokers, the proportion of relapse was not significantly different," added the authors.
Looking at safety, Dr. Bourreille reported that just over half of patients in each group complained of adverse events, including diarrhea, arthralgia, constipation, and abdominal pain.
"One oral fungal infection occurred in one patient treated with S. boulardii," he added. "None of the drug-related AEs was serious."
Compliance was greater than 90% in both the treatment and placebo groups.
Dr. Bourreille conceded that the study was limited by the use of clinical relapse as an endpoint, versus relapse defined by endoscopic findings.
"Clinical recurrence was chosen as the primary endpoint because endoscopic evaluation was not deemed necessary for the surveillance of nonsevere CD," wrote the investigators. "Moreover, at the time the study was designed, the concept of mucosal healing was not considered to be as relevant as it now is."
They added, however, that biological parameters of inflammation "were measured at each visit to ensure that clinical recurrence was associated with objective inflammation."
Dr. Bourreille and several coauthors disclosed ties with multiple pharmaceutical companies, including Biocodex, the maker of S. boulardii. Two coauthors were Biocodex employees.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Major finding: The probiotic yeast Saccharomyces boulardii does not appear to have any beneficial effects for patients with Crohn’s disease who are in remission.
Data source: FLORABEST, a 52-week, randomized, double-blind, placebo-controlled, 32-center trial of S. boulardii in Crohn’s disease.
Disclosures: Dr. Bourreille and several coauthors disclosed ties with multiple pharmaceutical companies, including Biocodex, the maker of S. boulardii. Two coauthors were Biocodex employees.