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Intervenciones para el tratamiento de la colitis linfocítica

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References

References to studies included in this review

Calabrese 2007 {published data only}

Calabrese C, Fabbri A, Areni A, Zahlane D, Scialpi C, Di Febo G. Mesalazine with or without cholestyramine in the treatment of microscopic colitis: randomized controlled trial. Journal of Gastroenterology and Hepatology 2007;22(6):809‐14. CENTRAL

Fine 1999 {published data only}

Fine K, Ogunji F, Lee E, Lafon G, Tanzi M. Randomized, double‐blind, placebo‐controlled trial of bismuth subsalicylate for microscopic colitis. Gastroenterology 1999;116(4 Part 2):A880. CENTRAL

Latella 2010 {published data only}

Latella G, Angelucci E, Tsolaki A, Saltarelli P, Necozione S, Frieri G. Beclometasone dipropionate and mesalazine are equally effective in the treatment of lymphocytic colitis. Digestive and Liver Diseases 2010;42:S87. CENTRAL

Miehlke 2009 {published data only}

Miehlke S, Madisch A, Bethke B, Wonschik S, Kuhlisch E, Beckmann R, et al. Budesonide in lymphocytic colitis ‐ a randomized, double‐blind, placebo‐controlled trial. Gastroenterology 2007;132(4 Suppl 2):A131‐2. CENTRAL
Miehlke S, Madisch A, Karimi D, Wonschik S, Beckmann R, Kuhlisch E, et al. MON‐G‐338. Budesonide for treatment of lymphocytic colitis ‐ a randomized, double‐blind, placebo‐controlled trial. United European Gastroenterology Week. Paris, France, October 29, 2007. CENTRAL
Miehlke S, Madisch A, Karimi D, Wonschik S, Kuhlisch E, Beckmann R, et al. Budesonide is effective in treating lymphocytic colitis: a randomized double‐blind placebo‐controlled study. Gastroenterology 2009;136(7):2092‐100. CENTRAL

Pardi 2009 {published data only}

Pardi DS, Loftus EV, Tremaine WJ, Sandborn WJ. A randomized, double‐blind, placebo‐controlled trial of budesonide for the treatment of active lymphocytic colitis. Gastroenterology 2009;136(5 Suppl 1):A519‐20. CENTRAL

References to studies excluded from this review

Bauma 2015 {published data only}

Bouma G, Munch A. Microscopic colitis. Digestive Diseases 2015;33(2):208‐14. CENTRAL

Gentile 2015 {published data only}

Gentile N, Abdalla A, Khanna S, Smyrk T, Tremaine W, Faubion W, et al. Outcomes of patients with microscopic colitis treated with bismuth subsalicylate. Gastroenterology 2015;1:S483. CENTRAL

Jo 2014 {published data only}

Jo KJ, Kim EK, Kim YS. Microscopic colitis is a functional gastrointestinal disorder in Asia?. Journal of Gastroenterology and Hepatology 2014;29:243. CENTRAL

Loftus 2003 {published data only}

Loftus EV. Microscopic colitis: epidemiology and treatment. American Journal of Gastroenterology 2003;29(12 Suppl):S31‐6. CENTRAL

Madisch 2007 {published data only}

Madisch A, Wonschik S, Morgner A, Kuhlisch E, Bethke B, Stolte M, et al. Long‐term progress of lymphocytic colitis after inducing a clinical remission with budesonide. Gastroenterology2007; Vol. 132, issue 4 Suppl 1:A‐511. CENTRAL

Miehlke 2013 {published data only}

Miehlke, S. Microscopic colitis [Mikroskopische kolitis]. Medizinische Welt 2012;64(4):191‐4. CENTRAL

Nyhlin 2006 {published data only}

Nyhlin N, Bohr J, Eriksson S, Tysk C. Systematic review: microscopic colitis. Alimentary Pharmacology & Therapeutics 2006;23(11):1525‐34. CENTRAL

Pardi 2002 {published data only}

Pardi DS, Ramnath VR, Loftus EV, Tremaine WJ, Sandborn WJ. Lymphocytic colitis: Clinical features, treatment, and outcomes. American Journal of Gastroenterology 2002;97(11):2829‐33. CENTRAL

Pardi 2014 {published data only}

Pardi DS. Microscopic colitis. Clinics in Geriatric Medicine 2014;30(1):55‐65. CENTRAL

Parkes 2007 {published data only}

Parkes M. Microscopic Colitis. Medicine 2007;35(5):290‐1. CENTRAL

Rohatgi 2008 {published data only}

Rohatgi S, Ahuja V. A Randomized trial evaluating probiotic preparation Vsl#3 versus oral mesalamine in patients with active microscopic colitis. Gastroenterology 2008;134(4 suppl 1):A‐712. CENTRAL

Rohatgi 2015 {published data only}

Rohatgi S, Ahuja V, Makharia G, Rai T, Das T, Das P, et al. VSL#3 induces and maintains short term clinical response in patients with active microscopic colitis: a two‐phase randomised clinical trial. BMJ Open Gastroenterology 2015;2(1):e00018. CENTRAL

Stewart 2011 {published data only}

Stewart MJ, Seow CH, Storr MA. Prednisolone and budesonide for short‐ and long‐term treatment of microscopic colitis: systematic review and meta‐analysis. Clinical Gastroenterology & Hepatology 2011;9(10):881‐90. CENTRAL

Stroehlein 2004 {published data only}

Stroehlein JR. Microscopic Colitis. Current Opinion in Gastroenterology 2004;20(1):27‐31. CENTRAL

Tagkalidis 2002 {published data only}

Tagkalidis P, Bhathal P, Gibson P. Microscopic Colitis. Journal of Gastroenterology & Hepatology 2002;17(3):236‐48. CENTRAL

Taheri 2011 {published data only}

Taheri A, Sadighi A, Nikkhoo B, Farhangi E. Evaluation of effects and complications of probiotics in microscopic colitis, a double blind placebo control clinical trial. Gastroenterology 2011;1:S‐852. CENTRAL

Temmerman 2009 {published data only}

Temmerman F, Baert F. Collagenous and lymphocytic colitis: systematic review and update of the literature. Digestive Diseases 2009;27(Suppl 1):137‐45. CENTRAL

Triadafilopoulos 2014 {published data only}

Triadafilopoulos, G. Glucocorticoid therapy for gastrointestinal diseases. Expert Opinion on Drug Safety 2014;13(5):563‐72. CENTRAL

Tysk 2005 {published data only}

Tysk C, Bohr J, Olesen M, Eriksson S, Jarnerot G. Microscopic colitis‐‐more common cause of diarrhea than believed. Biopsies are the only way to diagnosis, drug treatment is effective. Lakartidningen 2005;102(32‐33):2210‐4. CENTRAL

Tysk 2009 {published data only}

Tysk C. Large intestine: Remission of lymphocytic colitis with budesonide. Nature Reviews Gastroenterology & Hepatology 2009;6:506‐7. CENTRAL

NCT00184171 {published data only}

NCT00184171. Treatment of microscopic colitis (collagenous colitis and lymphocytic colitis) with budesonide, bismuth or fiber. http://clinicaltrials.gov/ct2/show/NCT00184171 (accessed 17January 2014). CENTRAL

NCT01209208 {published data only}

NCT01209208. Double‐blind, double‐dummy, randomised, placebo‐controlled, multi‐centre phase III study on the efficacy and tolerability of a 8‐week treatment with budesonide vs. mesalazine vs. placebo in patients with lymphocytic colitis. http://clinicaltrials.gov/ct2/show/NCT01209208 (accessed 17January 2014). CENTRAL

Abdo 2001

Abdo AA, Zetler PJ, Halparin LS. Familial microscopic colitis. Candian Journal of Gastroenterology 2001;15(5):341‐3.

Agnarsdottir 2002

Agnarsdottir M, Gunnlaugsson O, Orvar KB, Cariglia N, Birgisson S, Bjornsson S, et al. Collagenous and lymphocytic colitis in Iceland. Digestive Diseases and Sciences 2002;47(5):1122‐8.

Baert 1999

Baert F, Wouters K, D'Haens G, Hoang P, Naegels S, D'Heygere F, et al. Lymphocytic colitis: a distinct clinical entity? A clinicopathological confrontation of lymphocytic and collagenous colitis. Gut 1999;45(3):375‐81.

Baert 2002

Baert F, Schmit A, D'Haens G, Dedeurwaerdere F, Louis E, Cabooter M, et al. Budesonide in collagenous colitis: a double‐blind placebo‐controlled trial with histologic follow‐up. Gastroenterology 2002;122(1):20‐5.

Baert 2004

Baert D, Coppens M, Burvenich P, De Cock G, Lagae J, Rasquin K, et al. Chronic diarrhoea in non collagenous microscopic colitis: therapeutic effect of cholestyramine. Acta Clinica Belgica 2004;59(5):258‐62.

Barta 2005

Barta Z, Mekkel G, Csipo I, Toth L, Szakall S, Szabo G, et al. Microscopic colitis: a retrospective study of clinical presentation in 53 patients. World Journal of Gastroenterology 2005;11(9):1351‐5.

Ben Soussan 2001

Ben Soussan E, Savoye G, Lemoine F, Ducastelle P, Colin R. Azathioprine as a treatment of refractory lymphocytic colitis. European Journal of Gastroenterology & Hepatology 2001;13(4):457‐8.

Bohr 1995

Bohr J, Tysk C, Eriksson S, Jarnerot G. Collagenous colitis in Orebro, Sweden, an epidemiological study 1984‐1993. Gut 1995;37(3):394‐7.

Bohr 1996

Bohr J, Tysk C, Eriksson S, Abrahamsson H, Jarnerot G. Collagenous colitis: a retrospective study of clinical presentation and treatment in 163 patients. Gut 1996;39(96):846‐51.

Bohr 1999

Bohr J, Olesen M, Jarnerot G. Budesonide and bismuth in microscopic colitis. Gut 1999;45:A202.

Bonderup 2003

Bonderup OK, Hansen JB, Birket‐Smith L, Vestergaard V, Teglbjaerg PS, Fallingborg J. Budesonide treatment of collagenous colitis: a randomised, double blind, placebo controlled trial with morphometric analysis. Gut 2003;52(2):248‐51.

Bonderup 2007

Bonderup O, Hansen J, Teglbjaerg P, Christensen L, Fallingborg J. Long‐term budesonide treatment of collagenous colitis ‐ a randomized, double‐blind, placebo‐controlled trial. United European Gastroenterology Week2007:No FP‐247.

Bonner 2000

Bonner GF, Petras RE, Cheong DM, Grewal ID, Breno S, Ruderman WB. Short‐ and long‐term follow‐up of treatment for lymphocytic and collagenous colitis. Inflammatory Bowel Diseases 2000;6(2):85‐91.

Chande 2005

Chande N, Driman DK, Reynolds RP. Collagenous colitis and lymphocytic colitis: patient characteristics and clinical presentation. Scandinavian Journal of Gastroenterology 2005;40(3):343‐7.

Chande 2008a

Chande N, McDonald JWD, MacDonald JK. Interventions for treating collagenous colitis. Cochrane Database of Systematic Reviews 2008, Issue 2. [DOI: 10.1002/14651858.CD003575.pub5]

Chopra 2006

Chopra A, Pardi D, Loftus EV, Tremaine WJ, Egan LJ, Faubion WA, et al. Budesonide in the treatment of inflammatory bowel disease: the first of experience in clinical practice. Inflammatory Bowel Diseases 2006;12(1):29‐32.

De Waele 1994

De Waele S, Janssens P, Hoang P, Laka A, Lagneaux G, Lambert M. An unusual cause of chronic diarrhea: lymphocytic colitis [Une cause inhabituelle de diarrhee chronique: la colite lymphocytaire]. Acta Clinica Belgica 1994;49(3‐4):168‐72.

Eijsbouts 1995

Eijsbouts AM, Witteman BJ, de Sevaux RG, Fennis JF, van Haelst UJ, Naber AH, et al. Undefined malabsorption syndrome with villous atrophy successfully reversed by treatment with cyclosporine. European Journal of Gastroenterology & Hepatology 1995;7(8):803‐6.

Einarsson 1992

Einarsson K, Eusufzai S, Johansson U, Lofberg R, Theodorsson E, Veress B. Villous atrophy of distal ileum and lymphocytic colitis in a woman with bile acid malabsorption. European Journal of Gastroenterology & Hepatology 1992;4(7):585‐90.

Fekih 2006

Fekih M, Ben Hriz F, Sassi A, Matri S, Filali A, Boubaker J. Microscopic colitis. A 20 case series. Tunisie Medicale 2006;84(7):403‐6.

Fernandez 1999

Fernández F, Salas A, Forne M, Esteve M, Espinos J, Viver J. Incidence of collagenous and lymphocytic colitis: A 5‐year population‐based study. American Journal of Gastroenterology 1999;94(2):418‐23.

Fernandez 2001

Fernandez‐Banares F, Esteve M, Salas A, Forne TM, Espinos JC, Martin‐Comin J, et al. Bile acid malabsorption in microscopic colitis and in previously unexplained functional chronic diarrhea. Digestive Diseases and Sciences 2001;46(10):2231‐8.

Fernandez 2003

Fernández F, Salas A, Esteve M, Espinos J, Forne M, Maria J. Collagenous and lymphocytic colitis: evaluation of clinical and histological features, response to treatment, and long‐term follow‐up. American Journal of Gastroenterology 2003;98(2):340‐7.

Fine 1998

Fine KD, Lee EL. Efficacy of open‐label bismuth subsalicylate for the treatment of microscopic colitis. Gastroenterology 1998;114(1):29‐36.

Fomegne 2005

Fomegne G, Gruselle P. Microscopic colitis [Les colites microscopiques]. Revue Médicale de Bruxelles 2005;26(1):43‐7.

Goff 1997

Goff JS, Barnett JL, Pelke T, Appelman HD. Collagenous colitis: histopathology and clinical course. American Journal of Gastroenterology 1997;92(1):57‐60.

Higgins 2011

Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S editor(s). Cochrane Handbook of Systematic Review of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

Hilmer 2006

Hilmer SN, Heap TR, Eckstein RP, Lauer CS, Shenfield GM. Microscopic colitis associated with exposure to lansoprazole. Medical Journal of Australia 2006;184(4):185‐6.

Hollerweger 2003

Hollerweger A, Macheiner P, Brunner W. Suspicion of microscopic colitis raised by sonographic examination. Journal of Clinical Ultrasound 2003;31(4):207‐10.

Jensen 2005

Jensen L, Munck LK. Elementary diet reduces diarrhoea associated with microscopic colitis. Scandinavian Journal of Gastroenterology 2005;40(12):1495‐6.

Kitchen 2002

Kitchen P, Levi J, Domizio P, Talbot I, Forbes A, Price A, et al. Microscopic colitis: the tip of the iceberg?. European Journal of Gastroenterology & Hepatology 2002;14(11):1199‐1204.

Mahmoud 2005

Mahmoud F, Khalife W, Elaprolu K, Khurana A. Microscopic colitis: a report of two cases. South Dakota Journal of Medicine 2005;58(4):149‐53.

Mennecier 1999

Mennecier D, Gros P, Bronstein JA, Thiolet C, Farret O. Chronic diarrhea due to lymphocytic colitis treated with piroxicam beta cyclodextrin [Diarrhee chronique secondaire a la prise de piroxicam beta‐cyclodextrine associee a une colite lymphocytaire]. Presse Médicale 1999;28(14):735‐7.

Miehlke 2002

Miehlke S, Heymer P, Bethke B, Bastlein E, Meier E, Bartram HP, et al. Budesonide treatment for collagenous colitis: a randomized, double‐blind, placebo‐controlled, multicenter trial. Gastroenterology 2002;123(4):978‐84.

Miehlke 2007b

Miehlke S, Madisch A, Bethke B, Morgner A, Kuhlish E, Henker C, et al. Budesonide for maintenance treatment of collagenous colitis ‐ a randomized, double‐blind, placebo‐controlled trial. United European Gastroenterology Week2007:No. PS‐M‐13.

Mullhaupt 1998

Mullhaupt B, Guller U, Anabitarte M, Guller R, Fried M. Lymphocytic colitis: clinical presentation and long term course. Gut 1998;43(5):629‐33.

Netzer 1997

Netzer P, Levkovits H, Zimmermann A, Halter F. Collagen colitis and lymphocytic (microscopic) colitis: different or common origin? [Kollagenkolitis und lymphozytare (mikroskopische) Kolitis: differente oder gemeinsame Genese?]. Zeitschrift für Gastroenterologie 1997;35(9):681‐90.

Olesen 2004a

Olesen M, Eroksson S, Bohe J, Jarnerot G, Tysk C. Microscopic colitis: a common diarrhoeal disease. An epidemiological study in Orebro, Sweden, 1993‐1998. Gut 2004;53(3):346‐50.

Olesen 2004b

Olesen M, Eriksson S, Bohr J, Jarnerot G, Tysk C. Lymphocytic colitis: a retrospective clinical study of 199 Swedish patients. Gut 2004;53(4):536‐41.

Pardi 2001

Pardi DS, Loftus EV, Tremaine WJ, Sandborn WJ. Treatment of refractory microscopic colitis with azathioprine and 6‐mercaptopurine. Gastroenterology 2001;120(6):1483‐4.

Pardi 2004a

Pardi DS, Smyrk TC, Kammer P, Loftus EV, Tremaine WJ, Schleck CD, et al. The epidemiology of microscopic colitis (MC): a population‐based study in Olmsted County, MN. Gastroenterology 2004;124:A124.

Pardi 2004b

Pardi DS. Microscopic colitis: an update. Inflammatory Bowel Disease 2004;10:860‐70.

Perk 1999

Perk G, Ackerman Z, Cohen P, Eliakim R. Lymphocytic colitis: a clue to an infectious trigger. Scandinavian Journal of Gastroenterology 1999;34(1):110‐2.

Persoz 2001

Persoz CF, Cornella F, Kaeser P, Rochat T. Ticlopidine‐induced interstitial pulmonary disease: a case report. Chest 2001;119(6):1963‐5.

Puri 1994

Puri AS, Khan EM, Kumar M, Pandey R, Choudhuri G. Association of lymphocytic (microscopic) colitis with tropical sprue. Journal of Gastroenterology and Hepatology 1994;9(1):105‐7.

Raclot 1994

Raclot G, Queneau PE, Ottignon Y, Angonin R, Monnot B, Leroy M, et al. Incidence of collagenous colitis: a retrospective study in the east of France. Gastroenterology 1994;106(4):A23.

Riddell 1992

Riddell RH, Tanaka M, Mazzoleni G. Non‐steroidal anti‐inflammatory drugs as a possible cause of collagenous colitis: a case‐control study. Gut 1992;33(5):683‐6.

Sandmeier 2004

Sandmeier D, Bouzourene H. Microscopic colitis with giant cells: a rare new histopathologic subtype?. International Journal of Surgical Pathology 2004;12(1):45‐8.

Schiller 2004

Schiller LR. Diagnosis and management of microscopic colitis syndrome. Journal of Clinical Gastroenterology 2004;38(Suppl 1):S27‐30.

Schünemann 2011

Schünemann HJ, Oxman AD, Vist GE, Higgins JPT, Deeks JJ, Glasziou P, et al. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JPT, Green S editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

Swensson 1999

Swensson O, Stuber E, Nickel T, Sticherling M, Ghohestani RF, Nitsche R, et al. Linear IgA disease associated with lymphocytic colitis. British Journal of Dermatology 1999;140(2):317‐21.

Teahon 1994

Teahon K, Webster AD, Price AB, Weston J, Bjarnason I. Studies on the enteropathy associated with primary hypogammaglobulinaemia. Gut 1994;35(9):1244‐9.

Ung 2002

Ung KA, Kilander A, Willen R, Abrahamsson H. Role of bile acids in lymphocytic colitis. Hepatogastroenterology 2002;49(44):432‐7.

Van Gossum 1998

Van Gossum A, Schmit A, Peny MO. Oral budesonide for lymphocytic colitis. American Journal of Gastroenterology 1998;93(2):270.

Varghese 2002

Varghese L, Galandiuk S, Tremaine WJ, Burgart LJ. Lymphocytic colitis treated with proctocolectomy and ileal J‐pouch‐anal anastomosis: report of a case. Diseases of the Colon and Rectum 2002;45(1):123‐6.

Vennamaneni 2001

Vennamaneni SR, Bonner GF. Use of azathioprine or 6‐mercaptopurine for treatment of steroid‐dependent lymphocytic and collagenous colitis. American Journal of Gastroenterology 2001;96(9):2798‐9.

Wang 1999

Wang N, Dumont J, Achkar E, Easley K, Petras R, Goldblum J. Colonic epithelial lymphocytosis without a thickened subepithelial collagen table: A clinicopathologic study of 40 cases supporting a heterogeneous entity. American Journal of Surgical Pathology 1999;23(9):1068.

Weidenhiller 2005

Weidenhiller M, Muller S, Schwab D, Hahn EG, Raithel M, Winterkamp S. Microscopic (collagenous and lymphocytic) colitis triggered by food allergy. Gut 2005;54(2):312‐3.

Wiedermann 2007

Wiedermann CJ, Zelger A. Lymphocytic colitis in a patient with psoriasis responsive to budesonide. Scandinavian Journal of Gastroenterology 2007;42(4):538‐9.

Yusuf 1999

Yusuf TE, Soemijarsih M, Arpaia A, Goldberg SL, Sottile VM. Chronic microscopic enterocolitis with severe hypokalemia responding to subtotal colectomy. Journal of Clinical Gastroenterology 1999;29(3):284‐8.

Zins 1995

Zins BJ, Sandborn WJ, Tremaine WJ. Collagenous and lymphocytic colitis: subject review and therapeutic alternatives. American Journal of Gastroenterology 1995;90(9):1394‐400.

References to other published versions of this review

Chande 2007

Chande N, McDonald JW, MacDonald JK. Interventions for treating lymphocytic colitis. Cochrane Database of Systematic Reviews 2007, Issue 1. [DOI: 10.1002/14651858.CD006096.pub2]

Chande 2008b

Chande N, McDonald JW, MacDonald JK. Interventions for treating lymphocytic colitis. Cochrane Database of Systematic Reviews 2008, Issue 2. [DOI: 10.1002/14651858.CD006096.pub3]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Calabrese 2007

Methods

Randomized, unblinded, open‐label study. N=41 with lymphocytic colitis (and 23 with collagenous colitis). Duration of the study was 6 months. Patients underwent a colonoscopy pre‐treatment. Twenty patients also underwent a colonoscopy at the end of 6 months.Randomization was performed with a computer generated list

Participants

Clinical: Chronic or recurrent non‐bloody diarrhea
Histological: Increased chronic inflammatory infiltrate (plasma cells, lymphocytes, eosinophils) in the lamina propria; increased number of intraepithelial lymphocytes, damage to surface epithelium, with flattening of epithelial cells or epithelial loss or both and detachment and minimal crypt architecture distortion. More than 20 intraepithelial lymphocytes per 100 epithelial cells in the absence of a thickened subepithelial collagen layer (< 10 um) was also required to diagnose lymphocytic colitis. Patients with a clear correlation between symptoms and assumption of drugs (e.g. NSAIDS, ticlopidine, PPI) were excluded

Interventions

Mesalazine 800 mg po tid (n=20) vs. mesalazine 800 mg po tid + cholestyramine 4 g po od (n=21) for 6 months

Outcomes

Clinical: Complete response was complete resolution of diarrhea. Partial response was improvement but not resolution of diarrhea
Histological: Normalization of histologic pattern at the end of 6 months

Notes

Biopsies were performed in a blinded fashion by a single pathologist

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomization was performed with a computer generated list

Allocation concealment (selection bias)

Unclear risk

Allocation concealment not described

Blinding (performance bias and detection bias)
All outcomes

High risk

Open‐labeled trial

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No dropouts were reported

Selective reporting (reporting bias)

Low risk

All expected outcomes were reported

Other bias

Low risk

The study appears to be free of other sources of bias

Fine 1999

Methods

Randomized, double‐blind, placebo‐controlled. Duration of study was 8 weeks
N=5. Each patient underwent 48‐hour stool collection before treatment and on the last 2 days of treatment. Stool weight and consistency were assessed based on standardized criteria. All patients underwent flexible sigmoidoscopy with standardized biopsy protocol pre‐ and post‐treatment. Randomization was by pulling pieces of paper out of a sealed box.

Participants

Clinical: 8 weeks of non‐bloody watery diarrhea (without steatorhea) and normal endoscopic appearance of the colonic mucosa.
Histological (including involvement of the distal colon): excess mononuclear inflammatory cells in the lamina propria and surface epithelium without significant neutrophilia or eosinophilic inflammation, numerous crypt abscesses, or granuloma; and no other evidence of Crohn's disease. For the histological outcome analysis, a histopathology score from 0 to 10 was based on the following parameters: surface epithelium assessed for micro‐ulceration, cell flattening, and mucin depletion (scored: 0 ‐ normal, 1 ‐ moderate, 2 ‐ severe); crypts (scored: 0 ‐ normal, 1 ‐ distorted architecture or cryptitis with neutrophils, 2 ‐ containing crypt abscesses); lamina propria cellularity (scored: 0 ‐ normal, 1 ‐ focally increased with neutrophils, mononuclear inflammatory cells, or both, 2 ‐ diffusely increased with neutrophils, mononuclear inflammatory cells, or both); number of intraepithelial lymphocytes within surface epithelium (scored 0 ‐ normal, 1 ‐ moderately increased, 2 ‐ significantly increased); number of intraepithelial lymphocytes within crypt epithelium (scored 0 ‐ normal, 1 ‐ moderately increased, 2 ‐ significantly increased).

Interventions

Bismuth subsalicylate (9 262 mg chewable tablets daily in 3 divided doses) versus placebo for 8 weeks

Outcomes

Clinical: improvement of diarrhea to passage of 2 or less formed or semi formed stools/day.
Histological: improvement of histopathology score by at least 50%

Notes

Patients were not to take antibiotics or anti‐inflammatory agents for minimum 6 weeks, and not to take antidiarrheals for minimum 2 weeks prior to the beginning of the study

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomization was performed by pulling pieces of paper out of a sealed box

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double blind, identical coloured and flavoured placebo

Incomplete outcome data (attrition bias)
All outcomes

Low risk

One patient dropped out of the placebo group

Selective reporting (reporting bias)

Low risk

All expected outcomes were reported

Other bias

Low risk

The study appears to be free of other potential sources of bias

Latella 2010

Methods

Randomized, unblinded, open‐label study. N=46 with lymphocytic colitis. Duration of study was 8 weeks, with a 6 and 12 month follow‐up. Patients were treated with either beclometasone dipropionate or mesalazine

Participants

Patients with clinical and histologically confirmed lymphocytic colitis

Clinical criteria: >3 watery/loose stools per day on average per week, history of diarrhea >4 weeks

Histological criteria: complete colonoscopy with colonic biopsies within the last 4 weeks before randomization and a histologically confirmed diagnosis of active lymphocytic colitis

Interventions

Beclometasone dipropionate 5 mg/day (n=18) vs beclometasone dipropionate 10 mg/day (n=13) vs mesalazine 2.4 g/day (n=15) for 8 weeks

Outcomes

The primary outcome was clinical remission at 8 weeks.Clinical remission was pre‐defined as no more than 3 soft or solid stools per day during the last week of treatment. Clinical relapse at 6 and 12 months, was pre‐defined as greater than 3 stools per day on more than 4 consecutive days

Notes

Additional information provided by the lead author

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer generated randomization sequence

Allocation concealment (selection bias)

Low risk

Centralized randomization scheme

Blinding (performance bias and detection bias)
All outcomes

High risk

Open label study

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No patients dropped out

Selective reporting (reporting bias)

Low risk

All expected outcomes were reported

Other bias

Low risk

The study appears to be free of other potential sources of bias

Miehlke 2009

Methods

Randomized, double‐blind, placebo‐controlled. Duration of study was 6 weeks. Open label budesonide was offered to non responders for a further 6 weeks. Patients underwent a colonoscopy including histology at baseline and 6 weeks. Randomization was performed with a computer generated list

Participants

Patients with lymphocytic colitis and chronic diarrhea.
Clinical: more than 3 watery/loose stools per day on average for at least 4 weeks
Histological: The intraepithelial lymphocytes had to be greater than 20/100 epithelial cells, with inflammation of the lamina propria

Interventions

Budesonide 9 mg/day (n = 21) or placebo (n = 21) for 6 weeks

Outcomes

The primary outcome was clinical remission at week 6. Clinical remission was pre‐defined as no more than 3 non‐watery stools per day. Secondary outcomes included histological remission or response and quality of life (SF‐36). Histological remission was defined as a reduction in the number of IEL <20 IEL /100 epithelial cells plus a reduction in lamina propria inflammation. Histological response was defined as >20 IEL/100 epithelial cells but reduction of more than 50% compared to baseline or reduction in lamina propria inflammation or both. Clinical remission at 3 weeks

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer generated randomization sequence

Allocation concealment (selection bias)

Low risk

Centralized sequence concealment

Blinding (performance bias and detection bias)
All outcomes

Low risk

Placebo and budesonide were administered in identical capsules. Histological samples were examined by a blinded pathologist

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Patient withdrawals and missing outcome data were reported and evenly distributed across treatment groups

Selective reporting (reporting bias)

Low risk

All expected outcomes were reported

Other bias

Low risk

The study appears to be free of other potential sources of bias

Pardi 2009

Methods

Randomized, double‐blind, placebo controlled study (N = 15)

A stool specimen and blood sample was taken from each participant at the start of the study

Patients took either budesonide (n = 11) or placebo (n = 4) for 8 weeks

At the end of treatment, patients had stool collection and sigmoidoscopy

Participants

Patients (>18 years) with diarrhea ‐ defined as greater than 4 bowel movements per day and greater than "mild" ‐ and currently on no treatment or despite active treatment. Lymphocytic colitis was confirmed histologically within one year of enrolment

Interventions

Budesonide (9 mg/day) compared to placebo

Outcomes

The primary outcome measure was satisfactory control of diarrhea during at least three of the last four weeks. The secondary outcome measures were 1) histologic improvement in post treatment colon biopsies compared to baseline biopsies and 2) side effects and time (in days) to recurrence of diarrhea after discontinuation of study drug

Notes

Additional information provided by the lead author

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer generated

Allocation concealment (selection bias)

Low risk

Sealed, opaque envelopes

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Identical placebo was not available from the sponsor at the time of the study. All research personnel including the pathologist were blinded to treatment assignment. Patients did not know treatment assignment unless they discovered what budesonide was supposed to look like. The authors did not formally assess whether patients knew which treatment they received

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There were no drop outs and no missing data

Selective reporting (reporting bias)

Low risk

All expected outcomes were reported

Other bias

Low risk

The study appears to be free of other potential sources of bias

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Bauma 2015

Not a randomized control trial

Gentile 2015

Not a randomized control trial

Jo 2014

Not a randomized control trial

Loftus 2003

Not a randomized control trial

Madisch 2007

Not a randomized controlled trial

Miehlke 2013

Not a randomized control trial

Nyhlin 2006

Not a randomized control trial

Pardi 2002

Not a randomized control trial

Pardi 2014

Not a randomized control trial

Parkes 2007

Not a randomized control trial

Rohatgi 2008

Abstract only, no sufficient details

Rohatgi 2015

No outcome specific to lymphocytic colitis

Stewart 2011

Not a randomized control trial

Stroehlein 2004

Not a randomized control trial

Tagkalidis 2002

Not a randomized control trial

Taheri 2011

This study assessed probiotics compared to placebo

The abstract did not report on clinical symptoms or histology

Authors reported mean defecation results without standard deviations

We tried contacting the authors to get the actual values, but we were unsuccessful in obtaining further data

Temmerman 2009

Not a randomized control trial

Triadafilopoulos 2014

Not a randomized control trial

Tysk 2005

Not a randomized control trial

Tysk 2009

Not a randomized controlled trial

Characteristics of ongoing studies [ordered by study ID]

NCT00184171

Trial name or title

Treatment of microscopic colitis (collagenous colitis and lymphocytic colitis) with budesonide, bismuth or fiber

Methods

Randomized, open‐label, active control, parallel group efficacy study

Participants

Patients aged > 17 years

Inclusion criteria: microscopic colitis verified with biopsies from the colon

Symptoms to such an extent that treatment is indicated

Informed consent

Interventions

Patients assigned to budesonide (9 mg/day) or bismuth and fiber for 8 weeks

Outcomes

Primary outcome: stool frequency and consistency
Secondary outcome: histological findings in biopsies from colon

Starting date

Start date: November 2001
Estimated study completion date: April 2014

Contact information

Study chair: Per G Farup, PhD, Norwegian University of Science and Technology

Notes

ClinicalTrials.gov identifier: NCT00184171

NCT01209208

Trial name or title

Double‐blind, double‐dummy, randomised, placebo‐controlled, multi‐centre phase III study on the efficacy and tolerability of a 8‐week treatment with budesonide vs. mesalazine vs. placebo in patients with lymphocytic colitis

Methods

Randomized, double‐blind, double‐dummy, parallel group efficacy study

Participants

Patients aged 18 to 90 years

Inclusion Criteria: symptoms and signs of indication of lymphocytic colitis

Signed informed consent

Interventions

Budesonide (9 mg/day), mesalazine (3 g/day) or placebo for 8 weeks

Outcomes

Primary outcome: rate of clinical remission at 8 weeks

Secondary outcome: proportion of patients with histological improvement at 8 weeks

Starting date

Start date: May 2010
Estimated study completion date: April 2015

Contact information

Principal Investigator: Professor Stephan Miehlke, Magen‐Darm‐Zentrum, IKE ‐ Internistische Kooperation Eppendorf, Hamburg, Germany

Notes

ClinicalTrials.gov identifier: NCT01209208

Data and analyses

Open in table viewer
Comparison 1. Bismuth subsalicylate versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clinical response Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 1.1

Comparison 1 Bismuth subsalicylate versus placebo, Outcome 1 Clinical response.

Comparison 1 Bismuth subsalicylate versus placebo, Outcome 1 Clinical response.

2 Histological response Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 1.2

Comparison 1 Bismuth subsalicylate versus placebo, Outcome 2 Histological response.

Comparison 1 Bismuth subsalicylate versus placebo, Outcome 2 Histological response.

Open in table viewer
Comparison 2. Budesonide versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clinical response Show forest plot

2

57

Risk Ratio (M‐H, Fixed, 95% CI)

2.03 [1.25, 3.33]

Analysis 2.1

Comparison 2 Budesonide versus placebo, Outcome 1 Clinical response.

Comparison 2 Budesonide versus placebo, Outcome 1 Clinical response.

2 Histological response Show forest plot

2

39

Risk Ratio (M‐H, Fixed, 95% CI)

2.44 [1.13, 5.28]

Analysis 2.2

Comparison 2 Budesonide versus placebo, Outcome 2 Histological response.

Comparison 2 Budesonide versus placebo, Outcome 2 Histological response.

3 Adverse events Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 2.3

Comparison 2 Budesonide versus placebo, Outcome 3 Adverse events.

Comparison 2 Budesonide versus placebo, Outcome 3 Adverse events.

Open in table viewer
Comparison 3. Mesalazine versus mesalazine + cholestyramine

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clinical response Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 3.1

Comparison 3 Mesalazine versus mesalazine + cholestyramine, Outcome 1 Clinical response.

Comparison 3 Mesalazine versus mesalazine + cholestyramine, Outcome 1 Clinical response.

2 Histological response Show forest plot

1

41

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.77, 1.28]

Analysis 3.2

Comparison 3 Mesalazine versus mesalazine + cholestyramine, Outcome 2 Histological response.

Comparison 3 Mesalazine versus mesalazine + cholestyramine, Outcome 2 Histological response.

Open in table viewer
Comparison 4. Beclometasone dipropionate versus mesalazine

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clinical response at 8 weeks Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 4.1

Comparison 4 Beclometasone dipropionate versus mesalazine, Outcome 1 Clinical response at 8 weeks.

Comparison 4 Beclometasone dipropionate versus mesalazine, Outcome 1 Clinical response at 8 weeks.

2 Maintenance of clinical response at 12 months Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Analysis 4.2

Comparison 4 Beclometasone dipropionate versus mesalazine, Outcome 2 Maintenance of clinical response at 12 months.

Comparison 4 Beclometasone dipropionate versus mesalazine, Outcome 2 Maintenance of clinical response at 12 months.

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Comparison 1 Bismuth subsalicylate versus placebo, Outcome 1 Clinical response.
Figures and Tables -
Analysis 1.1

Comparison 1 Bismuth subsalicylate versus placebo, Outcome 1 Clinical response.

Comparison 1 Bismuth subsalicylate versus placebo, Outcome 2 Histological response.
Figures and Tables -
Analysis 1.2

Comparison 1 Bismuth subsalicylate versus placebo, Outcome 2 Histological response.

Comparison 2 Budesonide versus placebo, Outcome 1 Clinical response.
Figures and Tables -
Analysis 2.1

Comparison 2 Budesonide versus placebo, Outcome 1 Clinical response.

Comparison 2 Budesonide versus placebo, Outcome 2 Histological response.
Figures and Tables -
Analysis 2.2

Comparison 2 Budesonide versus placebo, Outcome 2 Histological response.

Comparison 2 Budesonide versus placebo, Outcome 3 Adverse events.
Figures and Tables -
Analysis 2.3

Comparison 2 Budesonide versus placebo, Outcome 3 Adverse events.

Comparison 3 Mesalazine versus mesalazine + cholestyramine, Outcome 1 Clinical response.
Figures and Tables -
Analysis 3.1

Comparison 3 Mesalazine versus mesalazine + cholestyramine, Outcome 1 Clinical response.

Comparison 3 Mesalazine versus mesalazine + cholestyramine, Outcome 2 Histological response.
Figures and Tables -
Analysis 3.2

Comparison 3 Mesalazine versus mesalazine + cholestyramine, Outcome 2 Histological response.

Comparison 4 Beclometasone dipropionate versus mesalazine, Outcome 1 Clinical response at 8 weeks.
Figures and Tables -
Analysis 4.1

Comparison 4 Beclometasone dipropionate versus mesalazine, Outcome 1 Clinical response at 8 weeks.

Comparison 4 Beclometasone dipropionate versus mesalazine, Outcome 2 Maintenance of clinical response at 12 months.
Figures and Tables -
Analysis 4.2

Comparison 4 Beclometasone dipropionate versus mesalazine, Outcome 2 Maintenance of clinical response at 12 months.

Summary of findings for the main comparison. Bismuth subsalicylate versus placebo for treating lymphocytic colitis

Bismuth subsalicylate versus placebo for treating lymphocytic colitis

Patient or population: patients with active lymphocytic colitis
Settings: outpatient
Intervention: bismuth subsalicylate versus placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

control

bismuth vs placebo

Clinical response

0 per 10001

0 per 1000

RR 5.25
(0.94 to 1.90)

5
(1 study)

⊕⊝⊝⊝
very low,2,3

Histological response

500 per 10001

665 per 1000

(135 to 3300)

RR 1.33

(0.27 to 6.6)

5

(1 study)

⊕⊝⊝⊝
very low2,3

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Control group risk estimates come from control arm of meta‐analysis, based on included trials.
2 Downgraded one level due to unclear risk of bias for allocation concealment.
3 Downgraded two levels due to very sparse data (3 events).

Figures and Tables -
Summary of findings for the main comparison. Bismuth subsalicylate versus placebo for treating lymphocytic colitis
Summary of findings 2. Budesonide versus mesalazine for treating lymphocytic colitis

Budesonide versus mesalazine for treating lymphocytic colitis

Patient or population: patients with active lymphocytic colitis
Settings: outpatient
Intervention: budesonide versus placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

control

budesonide versus placebo

Clinical response

440 per 10001

893 per 1000
(550 to 1000)

RR 2.03
(1.25 to 3.33)

57
(2 studies)

⊕⊕⊝⊝

low2,3

Histological response

313 per 10001

763 per 1000
(353 to 1000)

RR 2.44

(1.13 to 5.28)

39
(2 studies)

⊕⊕⊝⊝

low4

Adverse events

143 per 10001

96 per 1000

(17 to 513)

RR 0.67

(0.12 to 3.59)

42
(1 study)

⊕⊕⊝⊝

low5

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Control group risk estimates come from control arm of meta‐analysis, based on included trials.
2 Downgraded one level due to unclear risk of bias for blinding or participants and personnel
3 Downgraded one level due to sparse data (39 events).
4 Downgraded two levels due to very sparse data (23 events).
5 Downgraded two levels due to very sparse data (5 events).

Figures and Tables -
Summary of findings 2. Budesonide versus mesalazine for treating lymphocytic colitis
Summary of findings 3. Mesalazine versus mesalazine + cholestyramine for treating lymphocytic colitis

Mesalazine versus mesalazine + cholestyramine for treating lymphocytic colitis

Patient or population: patients with maintenance of remission in lymphocytic colitis
Settings: outpatient
Intervention: Mesalazine versus mesalazine + cholestyramine

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

mesalazine

mesalazine plus cholestyramine

Clinical response

857 per 1000

849 per 1000

(660 to 1000)

RR 0.99
(0.77 to 1.28)

41
(1 study)

⊕⊕⊝⊝
low ,2,3

Histological response

857 per 1000

849 of 1000

(660 to 1000)

RR 0.99
(0.77 to 1.28)

41
(1 study)

⊕⊕⊝⊝
low ,2,3

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Control group risk estimates come from control arm of meta‐analysis, based on included trials.
2 Downgraded one level due to high risk of bias (no blinding) and unclear allocation concealment
3 Downgraded one level due to sparse data (35 events)

Figures and Tables -
Summary of findings 3. Mesalazine versus mesalazine + cholestyramine for treating lymphocytic colitis
Summary of findings 4. Beclometasone dipropionate versus mesalazine for treating lymphocytic colitis

Beclometasone dipropionate versus mesalazine for treating lymphocytic colitis

Patient or population: Patients with active or quiescent lymphocytic colitis
Settings: outpatient
Intervention: Beclometasone dipropionate versus mesalazine

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Mesalazine

beclometasone

Clinical response at 8 weeks

867 per 10001

841 per 1000

(650 to 1075)

RR 0.97

(0.75 to 1.24)

46
(1 study)

⊕⊕⊝⊝

low2,3

Maintenance of clinical response at 12 weeks

200 of 10001

258 per 1000

(80 to 836)

RR 1.29

(0.40 to 4.18)

46
(1 study)

⊕⊝⊝⊝

very low2,4

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Control group risk estimates come from control arm of meta‐analysis, based on included trials.
2 Downgraded one level due to high risk of bias (no blinding) .
3 Downgraded one level due to sparse data (39 events)
4 Downgraded two levels due to very sparse data (11 events)

Figures and Tables -
Summary of findings 4. Beclometasone dipropionate versus mesalazine for treating lymphocytic colitis
Table 1. Non‐randomized studies of therapies for lymphocytic colitis

Therapy

References

Antiallergic therapy

Weidenhiller 2005

Antibiotics

Baert 1999; Hilmer 2006; Mullhaupt 1998; Olesen 2004b; Puri 1994; Swensson 1999

Antidiarrheal agents

Baert 1999; Fekih 2006; Fernandez 2003; Hilmer 2006; Hollerweger 2003; Mullhaupt 1998; Olesen 2004b; Pardi 2002; Wang 1999

Azathioprine/6‐mercaptopurine

Ben Soussan 2001; Pardi 2001; Pardi 2002; Vennamaneni 2001

Bile acid binding agents

Baert 1999; Baert 2004; Einarsson 1992; Fernandez 2001; Fernandez 2003; Mahmoud 2005; Olesen 2004b; Pardi 2002; Ung 2002

Bismuth subsalicylate

Bohr 1999; Fine 1998; Pardi 2002

Budesonide

Barta 2005; Chopra 2006; Fomegne 2005; Hollerweger 2003; Olesen 2004b; Van Gossum 1998; Wiedermann 2007

Bulking agents

Olesen 2004b

Corticosteroids (traditional)

Baert 1999; Bonner 2000; Olesen 2004b; Fernandez 2003; Kitchen 2002; Pardi 2002; Persoz 2001; Sandmeier 2004; Swensson 1999; Wang 1999

Cyclosporine

Eijsbouts 1995

Dietary modification/ or elemental diet (check)

Fekih 2006; Baert 1999; Jensen 2005; Teahon 1994; Weidenhiller 2005

Probiotics

Rohatgi 2015; Taheri 2011

Spasmolytics

Mullhaupt 1998

Sulfasalazine/other 5‐ASA

Abdo 2001; Baert 1999; Bonner 2000; De Waele 1994; Fekih 2006; Fernandez 2003; Hollerweger 2003; Kitchen 2002; Mennecier 1999; Mullhaupt 1998; Netzer 1997;p Olesen 2004b; Pardi 2002; Perk 1999; Wang 1999

Surgery

Varghese 2002; Yusuf 1999

Figures and Tables -
Table 1. Non‐randomized studies of therapies for lymphocytic colitis
Comparison 1. Bismuth subsalicylate versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clinical response Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2 Histological response Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Figures and Tables -
Comparison 1. Bismuth subsalicylate versus placebo
Comparison 2. Budesonide versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clinical response Show forest plot

2

57

Risk Ratio (M‐H, Fixed, 95% CI)

2.03 [1.25, 3.33]

2 Histological response Show forest plot

2

39

Risk Ratio (M‐H, Fixed, 95% CI)

2.44 [1.13, 5.28]

3 Adverse events Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Figures and Tables -
Comparison 2. Budesonide versus placebo
Comparison 3. Mesalazine versus mesalazine + cholestyramine

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clinical response Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2 Histological response Show forest plot

1

41

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.77, 1.28]

Figures and Tables -
Comparison 3. Mesalazine versus mesalazine + cholestyramine
Comparison 4. Beclometasone dipropionate versus mesalazine

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clinical response at 8 weeks Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

2 Maintenance of clinical response at 12 months Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

Figures and Tables -
Comparison 4. Beclometasone dipropionate versus mesalazine