CHARLOTTE, N.C.—Bile acid sequestrants effectively treat microscopic colitis that is refractory to standard therapies, according to a large retrospective study.
“In one of the largest cohorts evaluating bile acid sequestrants in microscopic colitis, we show that nearly two-thirds of patients have either a partial or complete response. In addition, patients without bile acid malabsorption still respond to bile acid sequestrants, suggesting it may be an effective therapy for microscopic colitis irrespective of the presence of bile acid diarrhea,” said investigator June Tome, MD, who reported the results at the 2022 annual meeting of the American College of Gastroenterology (presentation 58).
Bile acid malabsorption has been proposed as a potential mechanism underlying microscopic colitis, but studies have been small and the results inconsistent, noted Dr. Tome, a third-year internal medicine resident at Mayo Clinic in Rochester, Minn.
Bile Acid as Treatment Target
Dr. Tome and her co-investigators aimed to evaluate the effectiveness of bile acid sequestrants in treating microscopic colitis and to assess the utility of bile acid testing to predict response. The study group included 282 adults diagnosed with microscopic colitis and treated with bile acid sequestrants at Mayo Clinic Rochester between 2010 and 2020.
Most of the participants (88%) were female and their mean age was 59 years. Almost half had lymphocytic colitis, the mean number of bowel movements per day was six and essentially all the patients had tried other medications.
The investigators assessed treatment response bile acid sequestrants at 12 weeks (±4 weeks). Response was based on clinical symptoms, using published criteria. Histologic response was not evaluated.
Recurrence was diagnosed in patients who had new-onset diarrhea after initial improvement, with no other discernible cause. Complete response was indicated by resolution of diarrhea. Partial response was indicated by a 50% or greater reduction in the number of bowel movements, while less than 50% improvement was considered nonresponse. Patients who discontinued treatment due to side effects were considered intolerant to the treatment.
Bile acid malabsorption was defined by elevated fasting serum C4 (>63.2 ng/mL) or 48-hour total fecal bile acid more than 2,337 mcmol/48 hours.
Successful Alone and in Combination
Approximately half the patients (49.3%) had a complete response to bile acid sequestrants, Dr. Tome reported. In the responding population, 65% received cholestyramine, 22% colesevelam and 13% colestipol. Partial responses were noted in 16.3% of patients, while 24.8% did not respond and 9.6% were intolerant to the medication.
“There were no differences in outcomes between bile acid sequestrants alone versus giving them with concurrent medications for microscopic colitis, such as loperamide, budesonide or bismuth, and dose was not associated with response,” she added.
In fact, no significant predictors of response emerged. Variables evaluated included age at diagnosis, smoking history, number of bowel movements per day, coexisting celiac disease, prior cholecystectomy and previous medications, Dr. Tome reported.
The median duration of follow-up was 4.5 years. After bile acid sequestrants were discontinued, 41.6% of patients relapsed at a median of 21 weeks, with a range of one to 172 weeks.
“Most patients in our study were able to discontinue other medications they were on, and patients who were on high doses of maintenance budesonide were able to reduce the dose while on concurrent bile acid sequestrants,” she noted.
Approximately one-third of patients had testing for bile acid malabsorption, of whom 56.7% were positive. No significant association was found between presence of bile acid malabsorption and response to this therapy as assessed by serum C4 or 48-hour total fecal bile acid.
Based on the results, Dr. Tome said, “bile acid sequestrants may be considered ... for patients who are not responding to first-line options, such as budesonide, or who are intolerant to corticosteroids.”
‘Impressive’ Response
Brian E. Lacy, PhD, MD, a neurogastroenterologist who is a professor of medicine and a consultant at Mayo Clinic in Jacksonville, Fla., noted that microscopic colitis can develop for many reasons, often as a result of prior viral or bacterial infection of the gastrointestinal tract (leading to a change in the gut microbiome), underlying or coincident celiac disease, and intake of certain medications. Budesonide treatment can have side effects and may not always be effective.
“We know that excess bile acids or inadequately absorbed bile acids can cause chronic diarrhea (due to an increase in the local concentration of dihydroxy bile acids in the colon). Bile acid diarrhea is generally well treated with bile acid sequestrants, although it has not previously been tested in a large study of patients with microscopic colitis,” he pointed out.
“This is a very interesting study of a large group of patients with microscopic colitis at a tertiary referral center. The finding that many patients responded to bile acid sequestrants is impressive, especially given that only approximately half [of patients tested] had evidence of bile acid malabsorption,” Dr. Lacy commented.
“The authors should be applauded. ... The data presented here provides clinicians with another treatment option for patients with microscopic colitis with an agent that is safe, generally well tolerated, and without significant side effects,” he said. “I hope the authors follow up on this novel study with a prospective study comparing this to budesonide.”
—Caroline Helwick
Drs. Lacy and Tome reported no relevant financial disclosures.
This article is from the February 2023 print issue.