Budesonide Versus Mesalamine in Microscopic Colitis: A Comparative Meta-analysis of Randomized Controlled Trials.

Abstract

Microscopic colitis (MC) is an inflammatory bowel disease of autoimmune origin that causes chronic watery diarrhea. Medications, including budesonide, mesalamine, loperamide, cholestyramine, and bismuth subsalicylate, are first-line therapies. Meanwhile, azathioprine, 6-mercaptopurine, and methotrexate are indicated for refractory MC. We aim to assess the efficacy and safety of budesonide compared with mesalamine for induction of remission in MC patients. We searched the Cochrane Library, Scopus, Web of Science, and PubMed for relevant clinical trials comparing either mesalamine or budesonide with a control group. We included the following outcomes: clinical remission (3 or fewer stools/day), daily stool weight, daily stool frequency, number of patients with clinical response <50% in the disease activity, and daily stool consistency. Safety end points included: any adverse event, serious adverse events, any adverse event-related discontinuation, abdominal discomfort, constipation, flatulence, nausea, dizziness, headache, bronchitis, nasopharyngitis, and depression. We conducted a meta-analysis model using the generic inverse variance method and performed a subgroup analysis based on the intervention administered. Nineteen randomized clinical trials were included. We found that after 6 weeks of follow-up, budesonide is associated with increased clinical remission rates compared with mesalamine [RR=2.46 (2.27, 2.67), and RR=2.24 (1.95, 2.57), respectively]. However, the test of subgroup difference revealed that the difference is not significant (P=0.25). After 8 weeks of follow-up, budesonide showed significantly higher clinical remission rates than mesalamine RR=2.29 (2.14, 2.45), and RR=1.7 (1.41, 2.05), respectively (P=0.003). Regarding the daily stool weight, patients in the budesonide group showed nonsignificant less stool weight [MD=-351.62 (-534.25, -168.99)] compared with mesalamine [MD=-104.3 (-372.34, 163.74)], P=0.14. However, daily stool frequency was significantly less in the budesonide group compared with mesalamine (P<0.001). Budesonide is associated with a significantly lower incidence of adverse events compared with mesalamine (P=0.002). Analysis of other safety endpoints was not significant between both groups. Budesonide was found to be better than mesalamine in MC patients in terms of clinical remission rate, especially after 8 weeks of follow-up. Budesonide also showed less incidence of adverse events. There is an urgent need for randomized, double-blinded clinical trials to provide direct and reliable evidence.