Budesonide Versus Mesalamine in Microscopic Colitis: A Comparative Meta-analysis of Randomized Controlled Trials.
Journal
Journal of clinical gastroenterology
ISSN: 1539-2031
Titre abrégé: J Clin Gastroenterol
Pays: United States
ID NLM: 7910017
Informations de publication
Date de publication:
18 Jul 2024
18 Jul 2024
Historique:
received:
04
09
2023
accepted:
24
04
2024
medline:
23
7
2024
pubmed:
23
7
2024
entrez:
23
7
2024
Statut:
aheadofprint
Résumé
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.
Sections du résumé
BACKGROUND
BACKGROUND
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.
OBJECTIVE
OBJECTIVE
We aim to assess the efficacy and safety of budesonide compared with mesalamine for induction of remission in MC patients.
METHODS
METHODS
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.
RESULTS
RESULTS
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.
CONCLUSIONS
CONCLUSIONS
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.
Identifiants
pubmed: 39042479
doi: 10.1097/MCG.0000000000002025
pii: 00004836-990000000-00329
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Références
Wall GC, Schirmer LL, Page MJ. Pharmacotherapy for microscopic colitis. Pharmacotherapy. 2007;27:425–433.
Baert F, Schmit A, D’Haens G, et al. Budesonide in collagenous colitis: a double-blind placebo-controlled trial with histologic follow-up. Gastroenterology. 2002;122:20–25.
Thorsen AJ. Noninfectious colitides: Collagenous colitis, lymphocytic colitis, diversion colitis, and chemically induced colitis. Clin Colon Rectal Surg. 2007;20:47–57.
Rivière P, Zerbib F. Microscopic colitis. Rev Med Interne. 2020;41:523–528.
Bonderup OK, Hansen JB, Teglbjárg PS, et al. Long-term budesonide treatment of collagenous colitis: a randomised, double-blind, placebocontrolled trial. Gut. 2009;58:68–72.
Miehlke S, Hansen JB, Madisch A, et al. Risk factors for symptom relapse in collagenous colitis after withdrawal of short-term budesonide therapy. Inflamm Bowel Dis. 2013;19:2763–2767.
Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009;6:e1000097.
Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions: Cochrane Book Series. 2008.
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) Guidelines | Found at. https://www.gradeworkinggroup.org/
Green S, Higgins P, Julian T, et al. Cochrane Handbook: Cochrane Reviews: Ch 8: Assessing risk of bias in included studies. In: Cochrane Handbook for: Systematic Reviews of Interventions. 2011:3–10.
RevMan 5 | Cochrane Community.
Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. Br Med J. 2003;327:557–560.
Tromm A, Griga T, Möllmann HW, et al. Budesonide for the treatment of collagenous colitis: First results of a pilot trial. Am J Gastroenterol. 1999;94:1871–1875.
Rohatgi S, Ahuja V, Makharia GK, et al. VSL#3 induces and maintains shortterm clinical response in patients with active microscopic colitis: a two-phase randomised clinical trial. BMJ Open Gastroenterol. 2015;2:1–10.
Wagner M, Lampinen M, Sangfelt P, et al. Budesonide treatment of patients with collagenous colitis restores normal eosinophil and T-cell activity in the colon. Inflamm Bowel Dis. 2010;16:1118–1126.
Wagner M, Peterson CGB, Stolt I, et al. Fecal eosinophil cationic protein as a marker of active disease and treatment outcome in collagenous colitis: a pilot study. Scand J Gastroenterol. 2011;46:849–854.
Walter SA, Münch A, Öst Å, et al. Anorectal function in patients with collagenous colitis in active and clinically quiescent phase, in comparison with healthy controls. Neurogastroenterol Motil. 2010;22:534–539.
Bajor A, Kilander A, Gälman C, et al. Budesonide treatment is associated with increased bile acid absorption in collagenous colitis. Aliment Pharmacol Ther. 2006;24:1643–1649.
Bonderup OK, Hansen JB, Birket-Smith L, et al. Budesonide treatment of collagenous colitis: a randomised, double blind, placebo controlled trial with morphometric analysis. Gut. 2003;52:248–251.
Calabrese C, Fabbri A, Areni A, et al. Mesalazine with or without cholestyramine in the treatment of microscopic colitis: randomized controlled trial. J Gastroenterol Hepatol. 2007;22:809–814.
Madisch A, Heymer P, Voss C, et al. Oral budesonide therapy improves quality of life in patients with collagenous colitis. Int J Colorectal Dis. 2005;20:312–316.
Miehlke S, Madisch A, Karimi D, et al. Budesonide Is Effective in Treating Lymphocytic Colitis: A Randomized Double-Blind Placebo-Controlled Study. Gastroenterology. 2009;136:2092–2100.
Miehlke S, Heymer P, Bethke B, et al. Budesonide treatment for collagenous colitis: a randomized, double-blind, placebo-controlled, multicenter trial. Gastroenterology. 2002;123:978–984.
Miehlke S, Madisch A, Kupcinskas L, et al. Budesonide is more effective than mesalamine or placebo in short-term treatment of collagenous colitis. Gastroenterology. 2014;146:1222–1230.e2.
Miehlke S, Madisch A, Bethke B, et al. Oral Budesonide for Maintenance Treatment of Collagenous Colitis: A Randomized, Double-Blind, Placebo-Controlled Trial. Gastroenterology. 2008;135:1510–1516.
Miehlke S, Aust D, Mihaly E, et al. Efficacy and Safety of Budesonide, vs Mesalazine or Placebo, as Induction Therapy for Lymphocytic Colitis. Gastroenterology. 2018;155:1795–1804.e3.
Münch A, Söderholm JD, Öst Å, et al. Increased transmucosal uptake of E. coli K12 in collagenous colitis persists after budesonide treatment. Am J Gastroenterol. 2009;104:679–685.
Münch A, Bohr J, Miehlke S, et al. Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial. Gut. 2016;65:47–56.
Rindom Krogsgaard L, Kristian Munck L, Bytzer P, et al. An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide. Scand J Gastroenterol. 2019;54:446–452.
Kafil TS, Nguyen TM, Patton PH, et al. Interventions for treating collagenous colitis. Cochrane Database Syst Rev. 2017;11:CD003575.
Miehlke S, Acosta MB, Bouma G, et al. Oral budesonide in gastrointestinal and liver disease: a practical guide for the clinician. J Gastroenterol Hepatol. 2018;33:1574–1581.
Miehlke S, Guagnozzi D, Zabana Y, et al. European guidelines on microscopic colitis: United European Gastroenterology (UEG) and European Microscopic Colitis Group (EMCG) statements and recommendations. United Eur Gastroenterol J. 2020;9:13–37.
Tangri V, Chande N. Use of budesonide in the treatment of microscopic colitis. Saudi J Gastroenterol. 2010;16:236–238.
Stewart MJ, Seow CH, Storr MA. Prednisolone and Budesonide for Short- and Long-Term Treatment of Microscopic Colitis: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2011;9:881–890.
Pardi DS, Tremaine WJ, Carrasco-Labra A. American Gastroenterological Association Institute Technical Review on the Medical Management of Microscopic Colitis. Gastroenterology. 2016;150:247–274.e11.
Miehlke S, Madisch A, Voss C, et al. Long-term follow-up of collagenous colitis after induction of clinical remission with budesonide. Aliment Pharmacol Ther. 2005;22:1115–1119.
Bonderup OK, Hansen JB, Madsen P, et al. Budesonide treatment and expression of inducible nitric oxide synthase mRNA in colonic mucosa in collagenous colitis. Eur J Gastroenterol Hepatol. 2006;18:1095–1099.
Nguyen GC, Smalley WE, Vege SS, et al. American Gastroenterological Association Institute Guideline on the Medical Management of Microscopic Colitis. Gastroenterology. 2016;150:242–246.
Jobse P, Flens MJ, Loffeld RJ. Collagenous colitis: description of a single centre series of 83 patients. Eur J Intern Med. 2009;20:499–502.