Budesonide safe, effective for microscopic colitis

Oral budesonide is effective and safe for short-term treatment of collagenous colitis.

Indeed, the finding supports the recent recommendation by the European Microscopic Colitis Group to make budesonide the "treatment of choice for active microscopic colitis," wrote Dr. Stephan Miehlke and colleagues in the May 1 issue of Gastroenterology (doi:10.1053/j.gastro.2014.01.019).

In a phase III study sponsored by the maker of budesonide, Dr. Miehlke of the Center for Digestive Diseases Eppendorf, in Hamburg, Germany, looked at 92 adult patients with histologically confirmed collagenous colitis.

Patients hailed from 31 international centers, and in addition to histology all also met the following criteria: more than four watery or soft stools on at least 4 days in the week before baseline; greater than three stools per day on average within the last 7 days before baseline; chronic diarrhea for at least 3 months; and a history of colonoscopy within 1 year of baseline.

For inclusion in the study, antidiarrheal medications had to have been discontinued by 2 weeks before baseline, and no other gastrointestinal comorbidities were permitted, such as Crohn’s disease or ulcerative colitis.

Patients were then assigned to one of three treatment groups: budesonide 9 mg once daily; mesalamine 3 g daily; or placebo.

Clinical remission was defined as having fewer than three stools per day in the week before the visit

At the end of the 8-week double-blind study period, the investigators found that budesonide significantly reduced the mean number of watery stools per week from 29.7 to 2.4 (P less than.0001) and increased the mean number of solid stools per week from 0.3 to 6.7 (P less than.0001).

This corresponded with a Kaplan-Meier analysis revealing that the time to clinical remission was significantly shorter for patients taking budesonide (median 7 days), compared with placebo (median 21 days; P =.0144) or mesalamine (median 24 days; P =.0071).

Dr. Miehlke also obtained follow-up biopsies on 63 patients at the 8-week mark, including 23 budesonide patients, 18 taking mesalamine, and 22 placebo patients.

Ultimately, 87% of budesonide patients had histologic posttreatment remission, versus 50% of placebo patients (P =.0106) and 45% of mesalamine patients.

Looking at safety, while the authors reported that the rates of adverse events were similar between cohorts, none of the adverse events in the budesonide group were considered drug related.

The most frequent adverse events in all groups included headache, nasopharyngitis, and dyspepsia.

Dr. Miehlke postulated several possible reasons for budesonide’s efficacy in the microscopic colitis cohort.

"First, it exerts a well-documented and potent anti-inflammatory effect in the terminal ileum and right colon, as clearly shown in Crohn’s disease," he wrote.

"In addition, budesonide improves bile acid malabsorption, which might occur in a substantial number of patients with microscopic colitis, by up-regulating the bile acid transporter gene expression in the small bowel."

Finally, "there is evidence that budesonide improves the small intestine’s water-absorption capacity, lowering the ileostomy output in quiescent Crohn’s disease," he concluded.

The investigators disclosed that the study was sponsored by Dr Falk Pharma GmbH, the maker of budesonide. Dr. Miehlke and several coinvestigators also disclosed financial relationships with Dr Falk Pharma GmbH; two others are employees of the company.

Oral budesonide is effective and safe for short-term treatment of collagenous colitis.

Indeed, the finding supports the recent recommendation by the European Microscopic Colitis Group to make budesonide the "treatment of choice for active microscopic colitis," wrote Dr. Stephan Miehlke and colleagues in the May 1 issue of Gastroenterology (doi:10.1053/j.gastro.2014.01.019).

In a phase III study sponsored by the maker of budesonide, Dr. Miehlke of the Center for Digestive Diseases Eppendorf, in Hamburg, Germany, looked at 92 adult patients with histologically confirmed collagenous colitis.

Patients hailed from 31 international centers, and in addition to histology all also met the following criteria: more than four watery or soft stools on at least 4 days in the week before baseline; greater than three stools per day on average within the last 7 days before baseline; chronic diarrhea for at least 3 months; and a history of colonoscopy within 1 year of baseline.

For inclusion in the study, antidiarrheal medications had to have been discontinued by 2 weeks before baseline, and no other gastrointestinal comorbidities were permitted, such as Crohn’s disease or ulcerative colitis.

Patients were then assigned to one of three treatment groups: budesonide 9 mg once daily; mesalamine 3 g daily; or placebo.

Clinical remission was defined as having fewer than three stools per day in the week before the visit

At the end of the 8-week double-blind study period, the investigators found that budesonide significantly reduced the mean number of watery stools per week from 29.7 to 2.4 (P less than.0001) and increased the mean number of solid stools per week from 0.3 to 6.7 (P less than.0001).

This corresponded with a Kaplan-Meier analysis revealing that the time to clinical remission was significantly shorter for patients taking budesonide (median 7 days), compared with placebo (median 21 days; P =.0144) or mesalamine (median 24 days; P =.0071).

Dr. Miehlke also obtained follow-up biopsies on 63 patients at the 8-week mark, including 23 budesonide patients, 18 taking mesalamine, and 22 placebo patients.

Ultimately, 87% of budesonide patients had histologic posttreatment remission, versus 50% of placebo patients (P =.0106) and 45% of mesalamine patients.

Looking at safety, while the authors reported that the rates of adverse events were similar between cohorts, none of the adverse events in the budesonide group were considered drug related.

The most frequent adverse events in all groups included headache, nasopharyngitis, and dyspepsia.

Dr. Miehlke postulated several possible reasons for budesonide’s efficacy in the microscopic colitis cohort.

"First, it exerts a well-documented and potent anti-inflammatory effect in the terminal ileum and right colon, as clearly shown in Crohn’s disease," he wrote.

"In addition, budesonide improves bile acid malabsorption, which might occur in a substantial number of patients with microscopic colitis, by up-regulating the bile acid transporter gene expression in the small bowel."

Finally, "there is evidence that budesonide improves the small intestine’s water-absorption capacity, lowering the ileostomy output in quiescent Crohn’s disease," he concluded.

The investigators disclosed that the study was sponsored by Dr Falk Pharma GmbH, the maker of budesonide. Dr. Miehlke and several coinvestigators also disclosed financial relationships with Dr Falk Pharma GmbH; two others are employees of the company.

Oral budesonide is effective and safe for short-term treatment of collagenous colitis.

Indeed, the finding supports the recent recommendation by the European Microscopic Colitis Group to make budesonide the "treatment of choice for active microscopic colitis," wrote Dr. Stephan Miehlke and colleagues in the May 1 issue of Gastroenterology (doi:10.1053/j.gastro.2014.01.019).

In a phase III study sponsored by the maker of budesonide, Dr. Miehlke of the Center for Digestive Diseases Eppendorf, in Hamburg, Germany, looked at 92 adult patients with histologically confirmed collagenous colitis.

Patients hailed from 31 international centers, and in addition to histology all also met the following criteria: more than four watery or soft stools on at least 4 days in the week before baseline; greater than three stools per day on average within the last 7 days before baseline; chronic diarrhea for at least 3 months; and a history of colonoscopy within 1 year of baseline.

For inclusion in the study, antidiarrheal medications had to have been discontinued by 2 weeks before baseline, and no other gastrointestinal comorbidities were permitted, such as Crohn’s disease or ulcerative colitis.

Patients were then assigned to one of three treatment groups: budesonide 9 mg once daily; mesalamine 3 g daily; or placebo.

Clinical remission was defined as having fewer than three stools per day in the week before the visit

At the end of the 8-week double-blind study period, the investigators found that budesonide significantly reduced the mean number of watery stools per week from 29.7 to 2.4 (P less than.0001) and increased the mean number of solid stools per week from 0.3 to 6.7 (P less than.0001).

This corresponded with a Kaplan-Meier analysis revealing that the time to clinical remission was significantly shorter for patients taking budesonide (median 7 days), compared with placebo (median 21 days; P =.0144) or mesalamine (median 24 days; P =.0071).

Dr. Miehlke also obtained follow-up biopsies on 63 patients at the 8-week mark, including 23 budesonide patients, 18 taking mesalamine, and 22 placebo patients.

Ultimately, 87% of budesonide patients had histologic posttreatment remission, versus 50% of placebo patients (P =.0106) and 45% of mesalamine patients.

Looking at safety, while the authors reported that the rates of adverse events were similar between cohorts, none of the adverse events in the budesonide group were considered drug related.

The most frequent adverse events in all groups included headache, nasopharyngitis, and dyspepsia.

Dr. Miehlke postulated several possible reasons for budesonide’s efficacy in the microscopic colitis cohort.

"First, it exerts a well-documented and potent anti-inflammatory effect in the terminal ileum and right colon, as clearly shown in Crohn’s disease," he wrote.

"In addition, budesonide improves bile acid malabsorption, which might occur in a substantial number of patients with microscopic colitis, by up-regulating the bile acid transporter gene expression in the small bowel."

Finally, "there is evidence that budesonide improves the small intestine’s water-absorption capacity, lowering the ileostomy output in quiescent Crohn’s disease," he concluded.

The investigators disclosed that the study was sponsored by Dr Falk Pharma GmbH, the maker of budesonide. Dr. Miehlke and several coinvestigators also disclosed financial relationships with Dr Falk Pharma GmbH; two others are employees of the company.