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AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis

Published:January 13, 2020DOI:https://doi.org/10.1053/j.gastro.2020.01.006
      This document presents the official recommendations of the American Gastroenterological Association (AGA) on the management of moderate to severe ulcerative colitis (UC). The guideline was developed by the AGA Institute’s Clinical Guidelines Committee and approved by the AGA Governing Board. It is accompanied by a technical review that provides a detailed synthesis of the evidence from which these recommendations were formulated.
      • Singh S.
      • Allegretti J.R.
      • Siddique S.M.
      • et al.
      AGA Technical review on the management of moderate to severe ulcerative colitis.
      Development of this guideline and the accompanying technical review was fully funded by the AGA Institute without additional outside funding. Members of the guideline panel and technical review panel were selected by the AGA Governing Board in consultation with the Clinical Guidelines Committee with careful consideration of all Institute of Medicine recommendations for clinical guideline development. Joseph Feuerstein was the guideline panel chair and Siddharth Singh was the methodologist and co-chair of the guideline panel. A patient representative was also included in the development and review process and had no recommended changes. The guideline and accompanying technical review underwent independent peer review, and a 30-day open public comment period; all comments were collated by the AGA staff, and were reviewed and carefully considered by the guideline panel and technical review teams, respectively. Changes were incorporated in revised documents, and where changes were not accepted, a thoughtful response document was created. After the public comment period, 2 pivotal clinical trials (VARSITY, UNIFI) were published and a critical safety update on tofacitinib was issued by the US Food and Drug Administration (FDA). At the recommendation of the Clinical Guidelines Committee, the technical review and clinical guidelines were updated to incorporate this new evidence as presented here. In accordance with the Clinical Guidelines Committee policies, all clinical guidelines are reviewed annually at the AGA Clinical Guideline Committee meeting for new information. The next update for these guidelines is anticipated in 3 years from publication.

      Abbreviations used in this paper:

      AGA (American Gastroenterological Association), 5-ASA (5-aminosalicylate), ASUC (acute severe ulcerative colitis), CI (confidence interval), FDA (US Food and Drug Administration), GRADE (Grading of Recommendations Assessment, Development and Evaluation), OR (odds ratio), RCT (randomized controlled trial), RR (relative risk), UC (ulcerative colitis)
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      References

        • Singh S.
        • Allegretti J.R.
        • Siddique S.M.
        • et al.
        AGA Technical review on the management of moderate to severe ulcerative colitis.
        Gastroenterology. 2019; 158: 1465-1496
        • Fumery M.
        • Singh S.
        • Dulai P.S.
        • et al.
        Natural history of adult ulcerative colitis in population-based cohorts: a systematic review.
        Clin Gastroenterol Hepatol. 2018; 16: 343-356 e3
        • Narula N.
        • Marshall J.K.
        • Colombel J.F.
        • et al.
        Systematic review and meta-analysis: infliximab or cyclosporine as rescue therapy in patients with severe ulcerative colitis refractory to steroids.
        Am J Gastroenterol. 2016; 111: 477-491
        • Dassopoulos T.
        • Cohen R.D.
        • Scherl E.J.
        • et al.
        Ulcerative colitis care pathway.
        Gastroenterology. 2015; 149: 238-245
        • Schroeder K.W.
        • Tremaine W.J.
        • Ilstrup D.M.
        Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study.
        N Engl J Med. 1987; 317: 1625-1629
        • Truelove S.C.
        • Witts L.J.
        Cortisone in ulcerative colitis; final report on a therapeutic trial.
        Br Med J. 1955; 2: 1041-1048
        • Ungaro R.
        • Mehandru S.
        • Allen P.B.
        • et al.
        Ulcerative colitis.
        Lancet. 2017; 389: 1756-1770
        • Ko C.W.
        • Singh S.
        • Feuerstein J.D.
        • et al.
        American Gastroenterological Association Institute guideline on the management of mild-to-moderate ulcerative colitis.
        Gastroenterology. 2019; 156: 748-764
        • Feuerstein J.D.
        • Nguyen G.C.
        • Kupfer S.S.
        • et al.
        American Gastroenterological Association Institute Guideline on therapeutic drug monitoring in inflammatory bowel disease.
        Gastroenterology. 2017; 153: 827-834
        • American Gastroenterological Association
        AGA Institute Clinical Practice Guideline Development Process.
        American Gastroenterological Association, Bethesda, MD2018
        • Sultan S.
        • Falck-Ytter Y.
        • Inadomi J.M.
        The AGA Institute process for developing clinical practice guidelines part one: grading the evidence.
        Clin Gastroenterol Hepatol. 2013; 11: 329-332
        • Institute of Medicine
        Clinical Practice Guidlines We Can Trust.
        National Academies Press, Washington, DC2011
        • Singh S.
        • Murad M.H.
        • Fumery M.
        • Dulai P.S.
        • Sandborn W.J.
        First- and second-line pharmacotherapies for patients with moderate to severely active ulcerative colitis: an updated network meta-analysis.
        Clin Gastroenterol Hepatol. 2020; (Jan 13 [Online ahead of print]. https://doi.org/10.1016/j.cgh.2020.01.008.)
        • Cipriani A.
        • Higgins J.P.
        • Geddes J.R.
        • et al.
        Conceptual and technical challenges in network meta-analysis.
        Ann Intern Med. 2013; 159: 130-137
        • Caprilli R.
        • Carratu R.
        • Babbini M.
        Double-blind comparison of the effectiveness of azathioprine and sulfasalazine in idiopathic proctocolitis. Preliminary report.
        Am J Dig Dis. 1975; 20: 115-120
        • Jewell D.P.
        • Truelove S.C.
        Azathioprine in ulcerative colitis: final report on controlled therapeutic trial.
        Br Med J. 1974; 4: 627-630
        • Mate-Jimenez J.
        • Hermida C.
        • Cantero-Perona J.
        • et al.
        6-Mercaptopurine or methotrexate added to prednisone induces and maintains remission in steroid-dependent inflammatory bowel disease.
        Eur J Gastroenterol Hepatol. 2000; 12: 1227-1233
        • Rosenberg J.L.
        • Wall A.J.
        • Levin B.
        • et al.
        A controlled trial of azathioprine in the management of chronic ulcerative colitis.
        Gastroenterology. 1975; 69: 96-99
        • Sood A.
        • Midha V.
        • Sood N.
        • et al.
        Role of azathioprine in severe ulcerative colitis: one-year, placebo-controlled, randomized trial.
        Indian J Gastroenterol. 2000; 19: 14-16
        • Ardizzone S.
        • Maconi G.
        • Russo A.
        • et al.
        Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis.
        Gut. 2006; 55: 47-53
        • Hawthorne A.B.
        • Logan R.F.
        • Hawkey C.J.
        • et al.
        Randomised controlled trial of azathioprine withdrawal in ulcerative colitis.
        BMJ. 1992; 305: 20-22
        • Sood A.
        • Kaushal V.
        • Midha V.
        • et al.
        The beneficial effect of azathioprine on maintenance of remission in severe ulcerative colitis.
        J Gastroenterol. 2002; 37: 270-274
        • Sood A.
        • Midha V.
        • Sood N.
        • et al.
        Azathioprine versus sulfasalazine in maintenance of remission in severe ulcerative colitis.
        Indian J Gastroenterol. 2003; 22: 79-81
        • Herfarth H.
        • Barnes E.L.
        • Valentine J.F.
        • et al.
        Methotrexate is not superior to placebo in maintaining steroid-free response or remission in ulcerative colitis.
        Gastroenterology. 2018; 155: 1098-1108.e9
        • Oren R.
        • Arber N.
        • Odes S.
        • et al.
        Methotrexate in chronic active ulcerative colitis: a double-blind, randomized, Israeli multicenter trial.
        Gastroenterology. 1996; 110: 1416-1421
        • Panaccione R.
        • Ghosh S.
        • Middleton S.
        • et al.
        Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis.
        Gastroenterology. 2014; 146: 392-400.e3
        • Vermeire S.
        • Gils A.
        • Accossato P.
        • et al.
        Immunogenicity of biologics in inflammatory bowel disease.
        Therap Adv Gastroenterol. 2018; 11 (1756283X17750355)
        • Mantzaris G.J.
        • Sfakianakis M.
        • Archavlis E.
        • et al.
        A prospective randomized observer-blind 2-year trial of azathioprine monotherapy versus azathioprine and olsalazine for the maintenance of steroid-dependent ulcerative colitis.
        Am J Gastroenterol. 2004; 99: 1122-1128
        • Singh S.
        • Proudfoot J.A.
        • Dulai P.S.
        • et al.
        No benefit of concomitant 5-aminosalicylates in patients with ulcerative colitis escalated to biologic therapy: pooled analysis of individual participant data from clinical trials.
        Am J Gastroenterol. 2018; 113: 1197-1205
        • Nguyen G.C.
        • Gulamhusein A.
        • Bernstein C.N.
        5-aminosalicylic acid is not protective against colorectal cancer in inflammatory bowel disease: a meta-analysis of non-referral populations.
        Am J Gastroenterol. 2012; 107: 1298
        • O'Connor A.
        • Packey C.D.
        • Akbari M.
        • et al.
        Mesalamine, but not sulfasalazine, reduces the risk of colorectal neoplasia in patients with inflammatory bowel disease: an agent-specific systematic review and meta-analysis.
        Inflamm Bowel Dis. 2015; 21: 2562-2569
        • Rubin D.T.
        • Huo D.
        • Kinnucan J.A.
        • et al.
        Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case–control study.
        Clin Gastroenterol Hepatol. 2013; 11: 1601-1608. e4
        • Turner D.
        • Walsh C.M.
        • Steinhart A.H.
        • et al.
        Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression.
        Clin Gastroenterol Hepatol. 2007; 5: 103-110
        • Seo M.
        • Okada M.
        • Yao T.
        • et al.
        Evaluation of the clinical course of acute attacks in patients with ulcerative colitis through the use of an activity index.
        J Gastroenterol. 2002; 37: 29-34
        • Chapman R.W.
        • Selby W.S.
        • Jewell D.P.
        Controlled trial of intravenous metronidazole as an adjunct to corticosteroids in severe ulcerative colitis.
        Gut. 1986; 27: 1210-1212
        • Dickinson R.J.
        • O'Connor H.J.
        • Pinder I.
        Double blind controlled trial of oral vancomycin as adjunctive treatment in acute exacerbations of idiopathic colitis.
        Gut. 1985; 26: 1380-1384
        • Mantzaris G.J.
        • Hatzis A.
        • Kontogiannis P.
        • et al.
        Intravenous tobramycin and metronidazole as an adjunct to corticosteroids in acute, severe ulcerative colitis.
        Am J Gastroenterol. 1994; 89: 43-46
        • Mantzaris G.J.
        • Petraki K.
        • Archavlis E.
        • et al.
        A prospective randomized controlled trial of intravenous ciprofloxacin as an adjunct to corticosteroids in acute, severe ulcerative colitis.
        Scand J Gastroenterol. 2001; 36: 971-974
        • Jarnerot G.
        • Hertervig E.
        • Friis-Liby I.
        • et al.
        Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study.
        Gastroenterology. 2005; 128: 1805-1811
        • Lichtiger S.
        • Present D.H.
        • Kornbluth A.
        • et al.
        Cyclosporine in severe ulcerative colitis refractory to steroid therapy.
        N Engl J Med. 1994; 330: 1841-1845
        • Van Assche G.
        • D'Haens G.
        • Noman M.
        • et al.
        Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis.
        Gastroenterology. 2003; 125: 1025-1031
        • Laharie D.
        • Bourreille A.
        • Branche J.
        • et al.
        Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial.
        Lancet. 2012; 380: 1909-1915
        • Williams J.G.
        • Alam M.F.
        • Alrubaiy L.
        • et al.
        Infliximab versus ciclosporin for steroid-resistant acute severe ulcerative colitis (CONSTRUCT): a mixed methods, open-label, pragmatic randomised trial.
        Lancet Gastroenterol Hepatol. 2016; 1: 15-24
        • Choy M.C.
        • Seah D.
        • Gorelik A.
        • et al.
        Predicting response after infliximab salvage in acute severe ulcerative colitis.
        J Gastroenterol Hepatol. 2018; 33: 1347-1352
        • Gibson D.J.
        • Heetun Z.S.
        • Redmond C.E.
        • et al.
        An accelerated infliximab induction regimen reduces the need for early colectomy in patients with acute severe ulcerative colitis.
        Clin Gastroenterol Hepatol. 2015; 13: 330-335 e1
        • Govani S.M.
        • Waljee A.K.
        • Stidham R.W.
        • et al.
        Accelerated dosing of infliximab prevents colectomy within 90 days in only half of patients with severe ulcerative colitis.
        Gastroenterology. 2016; 150: S106
        • Shah S.C.
        • Naymagon S.
        • Cohen B.L.
        • et al.
        There is significant practice pattern variability in the management of the hospitalized ulcerative colitis patient at a tertiary care and IBD referral center.
        J Clin Gastroenterol. 2018; 52: 333-338
        • Brandse J.F.
        • van den Brink G.R.
        • Wildenberg M.E.
        • et al.
        Loss of infliximab into feces is associated with lack of response to therapy in patients with severe ulcerative colitis.
        Gastroenterology. 2015; 149: 350-355 e2