Abstract: Five RCTs (149 participants) met the inclusion criteria. These studies assessed bismuth subsalicylate versus placebo, budesonide versus placebo, mesalazine versus mesalazine plus cholestyramine and beclometasone dipropionate versus mesalazine. The study which assessed mesalazine versus mesalazine plus cholestyramine and the study which assessed beclometasone dipropionate versus mesalazine were judged to be at high risk of bias due to lack of blinding. The study which compared bismuth subsalicylate versus us placebo was judged as low quality due to a very small sample size and limited data. The other 3 studies were judged to be at low risk of bias. Budesonide (9 mg/day for 6 to 8 weeks) was significantly more effective than placebo for induction of clinical and histological response. Clinical response was noted in 88% of budesonide patients compared to 38% of placebo patients (2 studies; 57 participants; RR 2.03, 95% CI 1.25 to 3.33; GRADE = low). Histological response was noted in 78% of budesonide patients compared to 33% of placebo patients (2 studies; 39 patients; RR 2.44, 95% CI 1.13 to 5.28; GRADE = low). Forty-one patients were enrolled in the study assessing mesalazine (2.4 g/day) versus mesalazine plus cholestyramine (4 g/day). Clinical response was noted in 85% of patients in the mesalazine group compared to 86% of patients in the mesalazine plus cholestyramine group (RR 0.99, 95% CI 0.77 to 1.28; GRADE = low). Five patients were enrolled in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks versus placebo). There were no differences in clinical (P=0.10) or histological responses (P=0.71) in patients treated with bismuth subsalicylate compared with placebo (GRADE = very low). Forty-six patients were enrolled in the trial studying beclometasone dipropionate (5 mg/day or 10 mg/day) versus mesalazine (2.4 g/day). There were no differences in clinical remission at 8 weeks (RR 0.97; 95% CI 0.75 to 1.24; GRADE = low) and 12 months of treatment (RR 1.29; 95% CI 0.40 to 4.18; GRADE = very low). Although patients receiving beclometasone dipropionate (84%) and mesalazine (86%) achieved clinical remission at 8 weeks, it was not maintained at 12 months (26% and 20%, respectively). Adverse events reported in the budesonide studies include nausea, vomiting, neck pain, abdominal pain, hyperhidrosis and headache. Nausea and skin rash were reported as adverse events in the mesalazine study. Adverse events in the beclometasone dipropionate trial include nausea, sleepiness and change of mood. No adverse events were reported in the bismuth subsalicylate study. Low quality evidence suggests that budesonide may be effective for the treatment of active lymphocytic colitis. This benefit needs to be confirmed by a large placebo -controlled trial. Low quality evidence also suggests that mesalazine with or without cholestyramine and beclometasone dipropionate may be effective for the treatment of lymphocytic colitis, however this needs to be confirmed by large placebo-controlled studies. No conclusions can be made regarding bismuth subsalicylate due to the very small number of patients in the study, Further trials studying interventions for lymphocytic colitis are warranted.

Plain-language summary: Five studies including 149 participants were identified. These studies assessed budesonide versus placebo (e.g. a sugar pill), mesalazine versus mesalazine plus cholestyramine and beclometasone dipropionate versus mesalazine and Pepto-Bismol® versus placebo. The study which compared mesalazine to mesalazine plus cholestyramine and the study which compared beclometasone dipropionate to mesalazine were judged to be of low quality. The study which compared Pepto-Bismol® bismuth subsalicylate to a placebo was judged as low quality due to a very small sample size (5 participants) and limited data. The other three studies were judged to be high quality. A pooled analysis of two studies (57 participants) showed that budesonide (9 mg/day for 6 to 8 weeks) was superior to placebo for improvement of diarrhea and improvement of microscopic inflammation of the bowel. Improvement in diarrhea was noted in 88% of budesonide participants compared to 38% of placebo participants. Improvement in microscopic inflammation was reported in 78% of budesonide participants compared to 33% of placebo participants. Forty-one participants were enrolled in the study that compared mesalazine (2.4. g/day) to mesalazine plus cholestyramine (4 g/day). Improvement in diarrhea was noted in 85% of participants in the mesalazine group compared to 86% of participants in the mesalazine plus cholestyramine group. Five patients were enrolled in the trial studying Pepto-Bismol® (nine 262 mg tablets daily for 8 weeks versus placebo). There were no differences in improvement of diarrhea or in improvement of microscopic inflammation of the bowel. Forty-six participants were enrolled in the trial studying beclometasone dipropionate (5 mg/day or 10 mg/day) versus mesalazine (2.4 g/day). Although participants receiving beclometasone dipropionate (84%) and mesalazine (86%) had improved diarrhea at 8 weeks, this improvement was not maintained at 12 months (26% and 20%, respectively). Side effects reported in the budesonide studies include nausea, vomiting, neck pain, abdominal pain, excessive sweating and headache. Side effects reported in the mesalazine plus cholestyramine study included nausea and skin rash. Side effects in the beclometasone dipropionate trial included nausea, sleepiness and change of mood. No side effects were reported in the Pepto-Bismol® study. Low quality evidence suggests that budesonide may be an effective therapy for the treatment of lymphocytic colitis. Low quality evidence also suggests that mesalazine with or without cholestyramine and beclometasone dipropionate may be effective for treatment of lymphocytic colitis. No conclusions can be made regarding bismuth subsalicylate due to the very small number of participants in the study. In the future, researchers should consider further large placebo-controlled trials of budesonide to confirm the suggested benefit and safety of this therapy. Bismuth subsalicylate, which has less potential for toxicity than budesonide, also warrants further study. The effectiveness and safety of mesalazine with or without cholestyramine, and beclometasone dipropionate need to be investigated in a large placebo-controlled studies.