What is collagenous colitis?
Collagenous colitis is a type of microscopic colitis, a condition characterized by chronic watery non-bloody diarrhea. People with collagenous colitis have a normal appearing bowel when assessed by an endoscope (a camera used to look at the bowel); but have microscopic inflammation of the bowel when assessed by a biopsy (a tissue sample taken during endoscopy). The cause of this disorder is unknown.
What treatments have been tried for lymphocytic colitis?
Budesonide, mesalamine, cholestyramine, Boswellia serrata extract, probiotics, prednisolone and Pepto-Bismol® have been studied as treatment for collagenous colitis. Budesonide is an immunosuppressive steroid drug that is quickly metabolized by the liver resulting in reduced steroid-related side-effects. Prednisolone is a steroid drug used to treat inflammation. Mesalamine (also known as 5-ASA) is an anti-inflammatory drug. Cholestyramine is a drug that helps the body remove bile acids. Pepto-Bismol®, is an antacid medication used to treat discomforts of the stomach and gastrointestinal tract. Boswellia serrata extract is a herbal extract. Probiotics are found in yogurt or dietary supplements and contain potentially beneficial bacteria or yeast.
What did the researchers investigate?
The researchers investigated whether these treatments improve symptoms (e.g. diarrhea) or microscopic inflammation of collagenous colitis and whether any side effects (harms) result from treatment. The researchers searched the medical literature extensively up to 7 November 2016.
What did the researchers find?
Twelve studies (476 participants) were identified. Four studies were high quality. One study assessing mesalamine and cholestyramine was judged to be low quality and the other studies were judged to be of unclear quality due to poor reporting of methods.
Diarrhea resolved in 100% (4/4) of Pepto-Bismol® (nine 262 mg tablets daily for 8 weeks) participants compared to 0% (0/5) of placebo participants (1 study; very low quality evidence). Diarrhea resolved in 44% (7/16) of Boswellia serrata participants (three 400 mg/day capsules for 8 weeks) compared to 27% (4/15) of placebo participants (1 study; low-quality evidence). Diarrhea resolved in 80% (24/30) of budesonide participants compared to 44% (11/25) of mesalamine participants (1 study; low-quality evidence). There was no difference between the two treatments with respect to side effects. Diarrhea resolved in 44% (11/25) of mesalamine (3 g/day) participants compared to 59% (22/37) of placebo participants (1 study; low-quality evidence). There was no difference between the two treatments with respect to side effects. Diarrhea resolved in 63% (5/8) of prednisolone (50 mg/day for 2 weeks) participants compared to 0% (0/3) of placebo participants (1 study, low-quality evidence). Diarrhea resolved in 29% (6/21) of participants who received probiotics (2 capsules containing probiotics twice daily for 12 weeks) compared to 13% (1/8) of placebo participants (1 study, very low-quality evidence). Diarrhea resolved in 73% (8/11) of mesalamine (800 mg three times daily) participants compared to 100% (12/12) of mesalamine + cholestyramine participants (4 g daily) (1 study, very low-quality evidence). Diarrhea resolved in 81% (38/47) of budesonide (9 mg daily for 6-8 weeks) participants compared to 17% (8/47) of placebo participants (3 studies; low-quality evidence). Improvement in microscopic inflammation occurred in 72% (34/47) of budesonide participants compared to 17% (8/47) placebo participants (low-quality evidence). Resolution of diarrhea was maintained over 6 months in 68% (57/84) of budesonide participants compared to 20% (18/88) of placebo participants (3 studies, low-quality evidence). Improvement in microscopic inflammation was maintained in 48% (19/40) of budesonide participants compared to 15% (6/40) of placebo participants (2 studies; very low-quality evidence). No difference was found between budesonide and placebo for side effects (low-quality evidence) or serious side effects (very low-quality evidence). Side effects reported in the budesonide studies include nausea, vomiting, neck pain, abdominal pain, excessive sweating and headache. Side effects reported in the mesalamine studies included nausea and skin rash. Side effects in the prednisolone study included abdominal pain, headache, sleep disturbance, mood change and weight gain.
In conclusion, low quality evidence suggests that budesonide may be an effective therapy for active and inactive collagenous colitis. Due to small sample sizes and low study quality we are uncertain about the benefits and harms of therapy with Pepto-Bismol®, Boswellia serrata extract, mesalamine with or without cholestramine, prednisolone and probiotics. These agents and other therapies require further study.
Low quality evidence suggests that budesonide may be effective for inducing and maintaining clinical and histological response in patients with collagenous colitis. We are uncertain about the benefits and harms of therapy with bismuth subsalicylate, Boswellia serrata extract, mesalamine with or without cholestramine, prednisolone and probiotics. These agents and other therapies require further study.
Collagenous colitis is a cause of chronic diarrhea. This updated review was performed to identify therapies for collagenous colitis that have been assessed in randomized controlled trials (RCTs).
The primary objective was to assess the benefits and harms of treatments for collagenous colitis.
We searched CENTRAL, the Cochrane IBD Group Specialized Register, MEDLINE and EMBASE from inception to 7 November 2016.
We included RCTs comparing a therapy with placebo or active comparator for the treatment of active or quiescent collagenous colitis.
Data were independently extracted by two authors. The primary outcome was clinical response or maintenance of response as defined by the included studies. Secondary outcome measures included histological response, quality of life and the occurrence of adverse events. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The Cochrane risk of bias tool was used to assess bias. The overall quality of the evidence was assessed using the GRADE criteria.
Twelve RCTs (476 participants) were included. These studies assessed bismuth subsalicylate, Boswellia serrata extract, mesalamine, cholestyramine, probiotics, prednisolone and budesonide therapy. Four studies were low risk of bias. One study assessing mesalamine and cholestyramine was judged to be high risk of bias due to no blinding. The other studies had an unclear risk of bias for random sequence generation (five studies) allocation concealment (six studies), blinding (one study), incomplete outcome data (one study) and selective outcome reporting (one study). Clinical response occurred in 100% (4/4) of patients who received bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks) compared to 0% (0/5) of patients who received placebo (1 study; 9 participants; RR 10.80, 95% CI 0.75 to 155.93; GRADE = very low). Clinical response occurred in 44% (7/16) of patients who received Boswellia serrata extract (three 400 mg/day capsules for 8 weeks) compared to 27% (4/15) of patients who received placebo (1 study; 31 participants; RR 1.64, 95% CI 0.60 to 4.49; GRADE = low). Clinical response occurred in 80% (24/30) of budesonide patients compared to 44% (11/25) of mesalamine patients (1 study; 55 participants; RR 1.82, 95% CI 1.13 to 2.93; GRADE = low). Histological response was observed in 87% (26/30) of budesonide patients compared to 44% (11/25) of mesalamine patients (1 study, 55 participants; RR 1.97, 95% CI 1.24 to 3.13; GRADE = low). There was no difference between the two treatments with respect to adverse events (RR 0.69, 95% CI 0.43 to 1.10; GRADE = low), withdrawals due to adverse events (RR 0.09, 95% CI 0.01 to 1.65; GRADE = low) and serious adverse events (RR 0.12, 95% CI 0.01 to 2.21; GRADE = low). Clinical response occurred in 44% (11/25) of mesalamine patients (3 g/day) compared to 59% (22/37) of placebo patients (1 study; 62 participants; RR 0.74, 95% CI 0.44 to 1.24; GRADE = low). Histological response was observed in 44% (11/25) and 51% (19/37) of patients receiving mesalamine and placebo, respectively (1 study; 62 participants; RR 0.86, 95% CI 0.50 to 1.47; GRADE = low). There was no difference between the two treatments with respect to adverse events (RR 1.26, 95% CI 0.84 to 1.88; GRADE = low), withdrawals due to adverse events (RR 5.92, 95% CI 0.70 to 49.90; GRADE = low) and serious adverse events (RR 4.44, 95% CI 0.49 to 40.29; GRADE = low). Clinical response occurred in 63% (5/8) of prednisolone (50 mg/day for 2 weeks) patients compared to 0% (0/3) of placebo patients (1 study, 11 participants; RR 4.89, 95% CI 0.35 to 68.83; GRADE = very low). Clinical response occurred in 29% (6/21) of patients who received probiotics (2 capsules containing 0.5 x 1010 CFU each of L. acidophilus LA-5 and B. animalis subsp. lactis strain BB-12 twice daily for 12 weeks) compared to 13% (1/8) of placebo patients (1 study, 29 participants, RR 2.29, 95% CI 0.32 to 16.13; GRADE = very low). Clinical response occurred in 73% (8/11) of patients who received mesalamine (800 mg three times daily) compared to 100% (12/12) of patients who received mesalamine + cholestyramine (4 g daily) (1 study, 23 participants; RR 0.74, 95% CI 0.50 to 1.08; GRADE = very low). Clinical response occurred in 81% (38/47) of patients who received budesonide (9 mg daily in a tapering schedule for 6 to 8 weeks) compared to 17% (8/47) of placebo patients (3 studies; 94 participants; RR 4.56, 95% CI 2.43 to 8.55; GRADE = low). Histological response was higher in budesonide participants (72%, 34/47) compared to placebo (17%, 8/47) (RR 4.15, 95% CI 2.25 to 7.66; GRADE = low). Clinical response was maintained in 68% (57/84) of budesonide patients compared to 20% (18/88) of placebo patients (3 studies, 172 participants, RR 3.30 95% CI 2.13 to 5.09; GRADE = low). Histological response was maintained in 48% (19/40) of budesonide patients compared to 15% (6/40) of placebo patients (2 studies; 80 participants; RR 3.17, 95% CI 1.44 to 6.95; GRADE = very low). No difference was found between budesonide and placebo for adverse events (5 studies; 290 participants; RR 1.18, o95% CI 0.92 to 1.51; GRADE = low), withdrawals due to adverse events (5 studies, 290 participants; RR 0.97, 95% CI 0.43 to 2.17; GRADE = very low) or serious adverse events (4 studies, 175 participants; RR 1.11, 95% CI 0.15 to 8.01; GRADE = very low). Adverse effects reported in the budesonide studies include nausea, vomiting, neck pain, abdominal pain, excessive sweating and headache. Adverse effects reported in the mesalamine studies included nausea and skin rash. Adverse effects in the prednisolone study included abdominal pain, headache, sleep disturbance, mood change and weight gain.