Mucosal Healing in Ulcerative Colitis: A Comprehensive Review

Drugs

Volumn 77, Issue 2, 2017, Pages 159-173

  Boal Carvalho, Pedro ^a   Cotter, José ^a,b,c  

^a Hospital da Senhora da Oliveira Guimarães   (Portugal)

^b UNIVERSITY OF MINHO   (Portugal)

^c UNIVERSITY OF MINHO   (Portugal)

Author keywords

[No Author keywords available]

Indexed keywords

AGENTS USED IN INFLAMMATORY BOWEL DISEASE; AMINOSALICYLATE DERIVATIVE; ANTI INTEGRIN DRUG; CORTICOSTEROID; IMMUNOMODULATING AGENT; TUMOR NECROSIS FACTOR INHIBITOR; UNCLASSIFIED DRUG;

CLINICAL PRACTICE; ENDOSCOPY; HEALING; HISTOLOGY; HUMAN; MAYO ENDOSCOPIC SCORE 0; MAYO ENDOSCOPIC SCORE 1; MUCOSAL HEALING; PROGNOSIS; REVIEW; SCORING SYSTEM; ULCERATIVE COLITIS; COLITIS, ULCERATIVE; CYTOLOGY; DRUG EFFECTS; INTESTINE MUCOSA; PATHOLOGY; WOUND HEALING;

COLITIS, ULCERATIVE; HUMANS; INTESTINAL MUCOSA; WOUND HEALING;

EID: 85009286825     PISSN: 00126667     EISSN: 11791950     Source Type: Journal    
DOI: 10.1007/s40265-016-0676-y     Document Type: Review

References (114)

1. Dignass A, Eliakim R, Magro F, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 1: definitions and diagnosis. J Crohns Colitis. 2012;6:965–90.
2. Van Assche G, Dignass A, Panes J, et al. The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. J Crohns Colitis. 2010;4:7–27.
3. Dignass A, Lindsay JO, Sturm A, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J Crohns Colitis. 2012;6:991–1030.
4. Levesque BG, Sandborn WJ, Ruel J, et al. Converging goals of treatment of inflammatory bowel disease from clinical trials and practice. Gastroenterology. 2015;148(37–51):e1.
5. Van Assche G, Dignass A, Bokemeyer B, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 3: special situations. J Crohns Colitis. 2013;7:1–33.
6. Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955;2:1041–8.
7. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317:1625–9.
8. Colombel JF, Rutgeerts P, Reinisch W, et al. Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology. 2011;141:1194–201.
9. Lewis JD, Chuai S, Nessel L, et al. Use of the noninvasive components of the Mayo score to assess clinical response in ulcerative colitis. Inflamm Bowel Dis. 2008;14:1660–6.
10. Baars JE, Nuij VJ, Oldenburg B, et al. Majority of patients with inflammatory bowel disease in clinical remission have mucosal inflammation. Inflamm Bowel Dis. 2012;18:1634–40.
11. Rosenberg L, Lawlor GO, Zenlea T, et al. Predictors of endoscopic inflammation in patients with ulcerative colitis in clinical remission. Inflamm Bowel Dis. 2013;19:779–84.
12. Simren M, Axelsson J, Gillberg R, et al. Quality of life in inflammatory bowel disease in remission: the impact of IBS-like symptoms and associated psychological factors. Am J Gastroenterol. 2002;97:389–96.
13. Colombel JF, Keir ME, Scherl A, et al. Discrepancies between patient-reported outcomes, and endoscopic and histological appearance in UC. Gut. 2016. doi:10.1136/gutjnl-2016-312307 (Epub 2 Sep 2016).
14. Su C, Lewis JD, Goldberg B, et al. A meta-analysis of the placebo rates of remission and response in clinical trials of active ulcerative colitis. Gastroenterology. 2007;132:516–26.
15. Langholz E, Munkholm P, Davidsen M, et al. Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology. 1994;107:3–11.
16. Turner D, Walsh CM, Steinhart AH, et al. Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression. Clin Gastroenterol Hepatol. 2007;5:103–10.
17. Yoon JY, Park SJ, Hong SP, et al. Correlations of C-reactive protein levels and erythrocyte sedimentation rates with endoscopic activity indices in patients with ulcerative colitis. Dig Dis Sci. 2014;59:829–37.
18. Magro F, Lopes SI, Lopes J, et al. Histological outcomes and predictive value of faecal markers in moderately to severely active ulcerative colitis patients receiving infliximab. J Crohns Colitis. 2016;10(12):1407–16.
19. Guardiola J, Lobaton T, Rodriguez-Alonso L, et al. Fecal level of calprotectin identifies histologic inflammation in patients with ulcerative colitis in clinical and endoscopic remission. Clin Gastroenterol Hepatol. 2014;12:1865–70.
20. Magro F, Lopes S, Coelho R, et al. Accuracy of faecal Calprotectin and neutrophil gelatinase B-associated lipocalin in Evaluating sub-clinical inflammation in ulceRaTIVE colitis: the ACERTIVE study. J Crohns Colitis. 2016 (Epub 23 Sep 2016).
21. Peyrin-Biroulet L, Bressenot A, Kampman W. Histologic remission: the ultimate therapeutic goal in ulcerative colitis? Clin Gastroenterol Hepatol. 2014;12(929–34):e2.
22. Bessissow T, Lemmens B, Ferrante M, et al. Prognostic value of serologic and histologic markers on clinical relapse in ulcerative colitis patients with mucosal healing. Am J Gastroenterol. 2012;107:1684–92.
23. Bitton A, Peppercorn MA, Antonioli DA, et al. Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis. Gastroenterology. 2001;120:13–20.
24. Bryant RV, Burger DC, Delo J, et al. Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up. Gut. 2016;65:408–14.
25. Marchal Bressenot A, Riddell RH, Boulagnon-Rombi C, et al. Review article: the histological assessment of disease activity in ulcerative colitis. Aliment Pharmacol Ther. 2015;42:957–67.
26. Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699–710.
27. Rieder F, Karrasch T, Ben-Horin S, et al. Results of the 2nd scientific workshop of the ECCO (III): basic mechanisms of intestinal healing. J Crohns Colitis. 2012;6:373–85.
28. Nenci A, Becker C, Wullaert A, et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature. 2007;446:557–61.
29. McKenzie SJ, Baker MS, Buffinton GD, et al. Evidence of oxidant-induced injury to epithelial cells during inflammatory bowel disease. J Clin Invest. 1996;98:136–41.
30. von Lampe B, Barthel B, Coupland SE, et al. Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease. Gut. 2000;47:63–73.
31. Wehkamp J, Koslowski M, Wang G, et al. Barrier dysfunction due to distinct defensin deficiencies in small intestinal and colonic Crohn’s disease. Mucosal Immunol. 2008;1(Suppl 1):S67–74.
32. Bantel H, Berg C, Vieth M, et al. Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis. Am J Gastroenterol. 2000;95:3452–7.
33. Baumgart DC, Vierziger K, Sturm A, et al. Mesalamine promotes intestinal epithelial wound healing in vitro through a TGF-beta-independent mechanism. Scand J Gastroenterol. 2005;40:958–64.
34. Ardite E, Panes J, Miranda M, et al. Effects of steroid treatment on activation of nuclear factor kappaB in patients with inflammatory bowel disease. Br J Pharmacol. 1998;124:431–3.
35. Ancha HR, Kurella RR, McKimmey CC, et al. Luminal antioxidants enhance the effects of mesalamine in the treatment of chemically induced colitis in rats. Exp Biol Med (Maywood). 2008;233:1301–8.
36. D’Haens G, Geboes K, Rutgeerts P. Endoscopic and histologic healing of Crohn’s (ileo-) colitis with azathioprine. Gastrointest Endosc. 1999;50:667–71.
37. Baert FJ, D’Haens GR, Peeters M, et al. Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn’s ileocolitis. Gastroenterology. 1999;116:22–8.
38. Suenaert P, Bulteel V, Lemmens L, et al. Anti-tumor necrosis factor treatment restores the gut barrier in Crohn’s disease. Am J Gastroenterol. 2002;97:2000–4.
39. Lau MS, Tsai HH. Review of vedolizumab for the treatment of ulcerative colitis. World J Gastrointest Pharmacol Ther. 2016;7:107–11.
40. Daperno M, Castiglione F, de Ridder L, et al. Results of the 2nd part Scientific Workshop of the ECCO. II: measures and markers of prediction to achieve, detect, and monitor intestinal healing in inflammatory bowel disease. J Crohns Colitis. 2011;5:484–98.
41. D’Haens G, Sandborn WJ, Feagan BG, et al. A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis. Gastroenterology. 2007;132:763–86.
42. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–76.
43. Meucci G, Fasoli R, Saibeni S, et al. Prognostic significance of endoscopic remission in patients with active ulcerative colitis treated with oral and topical mesalazine: a prospective, multicenter study. Inflamm Bowel Dis. 2012;18:1006–10.
44. Boal Carvalho P, Dias de Castro F, Rosa B, et al. Mucosal healing in ulcerative colitis: when zero is better. J Crohns Colitis. 2016;10:20–5.
45. Barreiro-de Acosta M, Vallejo N, de la Iglesia D, et al. Evaluation of the risk of relapse in ulcerative colitis according to the degree of mucosal healing (Mayo 0 vs 1): a longitudinal cohort study. J Crohns Colitis. 2016;10:13–9.
46. Nakarai A, Kato J, Hiraoka S, et al. Prognosis of ulcerative colitis differs between patients with complete and partial mucosal healing, which can be predicted from the platelet count. World J Gastroenterol. 2014;20:18367–74.
47. Annese V, Daperno M, Rutter MD, et al. European evidence based consensus for endoscopy in inflammatory bowel disease. J Crohns Colitis. 2013;7:982–1018.
48. Baron JH, Connell AM, Lennard-Jones JE. Variation between observers in describing mucosal appearances in proctocolitis. Br Med J. 1964;1:89–92.
49. Ardizzone S, Cassinotti A, Duca P, et al. Mucosal healing predicts late outcomes after the first course of corticosteroids for newly diagnosed ulcerative colitis. Clin Gastroenterol Hepatol. 2011;9(483–9):e3.
50. Feagan BG, Greenberg GR, Wild G, et al. Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin. N Engl J Med. 2005;352:2499–507.
51. Rachmilewitz D. Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. BMJ. 1989;298:82–6.
52. Powell-Tuck J, Bown RL, Lennard-Jones JE. A comparison of oral prednisolone given as single or multiple daily doses for active proctocolitis. Scand J Gastroenterol. 1978;13:833–7.
53. Froslie KF, Jahnsen J, Moum BA, et al. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007;133:412–22.
54. Travis SP, Schnell D, Krzeski P, et al. Developing an instrument to assess the endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Gut. 2012;61:535–42.
55. Travis SP, Schnell D, Krzeski P, et al. Reliability and initial validation of the ulcerative colitis endoscopic index of severity. Gastroenterology. 2013;145:987–95.
56. Ikeya K, Hanai H, Sugimoto K, et al. The Ulcerative Colitis Endoscopic Index of Severity more accurately reflects clinical outcomes and long-term prognosis than the Mayo Endoscopic Score. J Crohns Colitis. 2016;10:286–95.
57. Samuel S, Bruining DH, Loftus EV Jr, et al. Validation of the ulcerative colitis colonoscopic index of severity and its correlation with disease activity measures. Clin Gastroenterol Hepatol. 2013;11(49–54):e1.
58. Travis SP, Schnell D, Feagan BG, et al. The impact of clinical information on the assessment of endoscopic activity: characteristics of the Ulcerative Colitis Endoscopic Index of Severity [UCEIS]. J Crohns Colitis. 2015;9:607–16.
59. Panes J, Feagan BG, Hussain F, et al. Central endoscopy reading in inflammatory bowel diseases. J Crohns Colitis. 2016;10(Suppl 2):S542–7.
60. Feagan BG, Sandborn WJ, D’Haens G, et al. The role of centralized reading of endoscopy in a randomized controlled trial of mesalamine for ulcerative colitis. Gastroenterology. 2013;145(149–57):e2.
61. Vermeire S, O’Byrne S, Keir M, et al. Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial. Lancet. 2014;384:309–18.
62. Dulai PS, Levesque BG, Feagan BG, et al. Assessment of mucosal healing in inflammatory bowel disease: review. Gastrointest Endosc. 2015;82(2):246–55.
63. Romkens TE, Kampschreur MT, Drenth JP, et al. High mucosal healing rates in 5-ASA-treated ulcerative colitis patients: results of a meta-analysis of clinical trials. Inflamm Bowel Dis. 2012;18:2190–8.
64. Lichtenstein GR, Ramsey D, Rubin DT. Randomised clinical trial: delayed-release oral mesalazine 4.8 g/day vs. 2.4 g/day in endoscopic mucosal healing—ASCEND I and II combined analysis. Aliment Pharmacol Ther. 2011;33:672–8.
65. Safdi M, DeMicco M, Sninsky C, et al. A double-blind comparison of oral versus rectal mesalamine versus combination therapy in the treatment of distal ulcerative colitis. Am J Gastroenterol. 1997;92:1867–71.
66. Sandborn WJ, Hanauer S, Lichtenstein GR, et al. Early symptomatic response and mucosal healing with mesalazine rectal suspension therapy in active distal ulcerative colitis: additional results from two controlled studies. Aliment Pharmacol Ther. 2011;34:747–56.
67. Rubin DT, Bradette M, Gabalec L, et al. Ulcerative colitis remission status after induction with mesalazine predicts maintenance outcomes: the MOMENTUM trial. J Crohns Colitis. 2016;10(8):925–33.
68. Naganuma M, Aoyama N, Suzuki Y, et al. Twice-daily budesonide 2-mg foam induces complete mucosal healing in patients with distal ulcerative colitis. J Crohns Colitis. 2016;10:828–36.
69. Sandborn WJ, Travis S, Moro L, et al. Once-daily budesonide MMX(R) extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study. Gastroenterology. 2012;143:1218–26.e1–2.
70. ®: a review of its use in patients with mild to moderate ulcerative colitis. Drugs. 2015;75:879–86.
71. 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.
72. Aloi M, D’Arcangelo G, Bramuzzo M, et al. Effect of early versus late azathioprine therapy in pediatric ulcerative colitis. Inflamm Bowel Dis. 2016;22:1647–54.
73. Lopez-Palacios N, Mendoza JL, Taxonera C, et al. Mucosal healing for predicting clinical outcome in patients with ulcerative colitis using thiopurines in monotherapy. Eur J Intern Med. 2011;22:621–5.
74. 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.
75. Ha C, Dassopoulos T. Thiopurine therapy in inflammatory bowel disease. Expert Rev Gastroenterol Hepatol. 2010;4:575–88.
76. Dassopoulos T, Dubinsky MC, Bentsen JL, et al. Randomised clinical trial: individualised vs. weight-based dosing of azathioprine in Crohn’s disease. Aliment Pharmacol Ther. 2014;39:163–75.
77. Wang Y, MacDonald JK, Vandermeer B, et al. Methotrexate for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2015;(8):CD007560.
78. Carbonnel F, Colombel JF, Filippi J, et al. Methotrexate is not superior to placebo for inducing steroid-free remission, but induces steroid-free clinical remission in a larger proportion of patients with ulcerative colitis. Gastroenterology. 2016;150(380–8):e4.
79. Ogata H, Kato J, Hirai F, et al. Double-blind, placebo-controlled trial of oral tacrolimus (FK506) in the management of hospitalized patients with steroid-refractory ulcerative colitis. Inflamm Bowel Dis. 2012;18:803–8.
80. Rosen MJ, Minar P, Vinks AA. Review article: applying pharmacokinetics to optimise dosing of anti-TNF biologics in acute severe ulcerative colitis. Aliment Pharmacol Ther. 2015;41:1094–103.
81. Lopez A, Ford AC, Colombel JF, et al. Efficacy of tumour necrosis factor antagonists on remission, colectomy and hospitalisations in ulcerative colitis: meta-analysis of placebo-controlled trials. Dig Liver Dis. 2015;47:356–64.
82. Reinisch W, Sandborn WJ, Hommes DW, et al. Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial. Gut. 2011;60:780–7.
83. Sandborn WJ, van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2012;142:257–65.e1–3.
84. Colombel JF, Sandborn WJ, Ghosh S, et al. Four-year maintenance treatment with adalimumab in patients with moderately to severely active ulcerative colitis: Data from ULTRA 1, 2, and 3. Am J Gastroenterol. 2014;109:1771–80.
85. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:85–95 (quiz e14–5).
86. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146(96–109):e1.
87. Yarur AJ, Kubiliun MJ, Czul F, et al. Concentrations of 6-thioguanine nucleotide correlate with trough levels of infliximab in patients with inflammatory bowel disease on combination therapy. Clin Gastroenterol Hepatol. 2015;13(1118–24):e3.
88. Ungar B, Levy I, Yavne Y, et al. Optimizing anti-TNF-alpha therapy: serum levels of infliximab and adalimumab are associated with mucosal healing in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2016;14(550–7):e2.
89. Vande Casteele N, Ferrante M, Van Assche G, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. Gastroenterology. 2015;148(1320–9):e3.
90. Adedokun OJ, Sandborn WJ, Feagan BG, et al. Association between serum concentration of infliximab and efficacy in adult patients with ulcerative colitis. Gastroenterology. 2014;147(1296–307):e5.
91. Barnes EL, Allegretti JR. Are anti-tumor necrosis factor trough levels predictive of mucosal healing in patients with inflammatory bowel disease? A systematic review and meta-analysis. J Clin Gastroenterol. 2016;50:733–41.
92. Ha C, Mathur J, Kornbluth A. Anti-TNF levels and anti-drug antibodies, immunosuppressants and clinical outcomes in inflammatory bowel disease. Expert Rev Gastroenterol Hepatol. 2015;9:497–505.
93. Ungar B, Chowers Y, Yavzori M, et al. The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab. Gut. 2014;63:1258–64.
94. Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362:1383–95.
95. Ordas I, Feagan BG, Sandborn WJ. Therapeutic drug monitoring of tumor necrosis factor antagonists in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2012;10:1079–87 (quiz e85–6).
96. Fasanmade AA, Adedokun OJ, Blank M, et al. Pharmacokinetic properties of infliximab in children and adults with Crohn’s disease: a retrospective analysis of data from 2 phase III clinical trials. Clin Ther. 2011;33:946–64.
97. Nanda KS, Cheifetz AS, Moss AC. Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease (IBD): a meta-analysis. Am J Gastroenterol. 2013;108:40–7 (quiz 8).
98. Gibson PR, Feagan BG, Sandborn WJ, et al. Maintenance of efficacy and continuing safety of golimumab for active ulcerative colitis: PURSUIT-SC maintenance study extension through 1 year. Clin Transl Gastroenterol. 2016;7:e168.
99. Wright R, Truelove SR. Serial rectal biopsy in ulcerative colitis during the course of a controlled therapeutic trial of various diets. Am J Dig Dis. 1966;11:847–57.
100. Parente F, Molteni M, Marino B, et al. Are colonoscopy and bowel ultrasound useful for assessing response to short-term therapy and predicting disease outcome of moderate-to-severe forms of ulcerative colitis?: a prospective study. Am J Gastroenterol. 2010;105:1150–7.
101. Rubin DT, LoSavio A, Yadron N, et al. Aminosalicylate therapy in the prevention of dysplasia and colorectal cancer in ulcerative colitis. Clin Gastroenterol Hepatol. 2006;4:1346–50.
102. Rutter M, Saunders B, Wilkinson K, et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis. Gastroenterology. 2004;126:451–9.
103. Rutter MD, Saunders BP, Wilkinson KH, et al. Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk. Gut. 2004;53:1813–6.
104. Velayos FS, Terdiman JP, Walsh JM. Effect of 5-aminosalicylate use on colorectal cancer and dysplasia risk: a systematic review and metaanalysis of observational studies. Am J Gastroenterol. 2005;100:1345–53.
105. Yokoyama K, Kobayashi K, Mukae M, et al. Clinical study of the relation between mucosal healing and long-term outcomes in ulcerative colitis. Gastroenterol Res Pract. 2013;2013:192794.
106. Neumann H, Vieth M, Gunther C, et al. Virtual chromoendoscopy for prediction of severity and disease extent in patients with inflammatory bowel disease: a randomized controlled study. Inflamm Bowel Dis. 2013;19:1935–42.
107. Iacucci M, Fort Gasia M, Hassan C, et al. Complete mucosal healing defined by endoscopic Mayo subscore still demonstrates abnormalities by novel high definition colonoscopy and refined histological gradings. Endoscopy. 2015;47:726–34.
108. Riley SA, Mani V, Goodman MJ, et al. Microscopic activity in ulcerative colitis: what does it mean? Gut. 1991;32:174–8.
109. Lichtenstein GR, Rutgeerts P. Importance of mucosal healing in ulcerative colitis. Inflamm Bowel Dis. 2010;16:338–46.
110. Zenlea T, Yee EU, Rosenberg L, et al. Histology grade is independently associated with relapse risk in patients with ulcerative colitis in clinical remission: a prospective study. Am J Gastroenterol. 2016;111:685–90.
111. Mosli MH, Feagan BG, Sandborn WJ, et al. Histologic evaluation of ulcerative colitis: a systematic review of disease activity indices. Inflamm Bowel Dis. 2014;20:564–75.
112. Mosli MH, Feagan BG, Zou G, et al. Development and validation of a histological index for UC. Gut. 2015. doi:10.1136/gutjnl-2015-310393 (Epub 16 Oct 2015).
113. Marchal-Bressenot A, Salleron J, Boulagnon-Rombi C, et al. Development and validation of the Nancy histological index for UC. Gut. 2015. doi:10.1136/gutjnl-2015-310187 (Epub 13 Oct 2015).
114. Lemmens B, Arijs I, Van Assche G, et al. Correlation between the endoscopic and histologic score in assessing the activity of ulcerative colitis. Inflamm Bowel Dis. 2013;19:1194–201.