A modern view on the management of patients with ulcerative colitis of mild and moderate severity in outpatient practice
https://doi.org/10.51793/OS.2022.25.2.004
Abstract
The article discusses modern approaches to the treatment of ulcerative colitis. It is indicated that for the choice of tactics and treatment algorithm, the extent of the lesion, as well as the severity of the current exacerbation, classified as mild, moderate and severe, are important. The criteria are useful for assessing the need for hospitalization, but do not take into account such important signs as nocturnal symptoms, extraintestinal manifestations, endoscopic activity. The severity of an exacerbation of a disease characterizes its severity at the moment, but may not reflect the long-term cumulative burden of the disease. The extent of the lesion, in turn, may influence the choice of route of administration. There are: proctitis (spread of inflammation to the rectosigmoid angle), left-sided (inflammation is limited to the splenic flexure) and widespread lesion (inflammation extends proximal to the splenic flexure, including pancolitis). To achieve the goals of therapy, the time period from the start of treatment to the expected clinical response, remission and endoscopic healing was determined. The immediate and short-term goals are clinical response and remission, as well as the normalization of the level of C-reactive protein. Reduction of fecal calprotectin to the optimal range is recommended as an official intermediate treatment goal. The degree of increase in the concentration of fecal calprotectin correlates with the severity of inflammation, and with a mild degree of the disease, its values may be normal or borderline. In this situation, repeated monitoring of fecal calprotectin over time can clarify the clinical picture. This was demonstrated in a recent prospective cohort study, where consistent determination of fecal calprotectin at 1-month intervals was the best predictor of exacerbation before the onset of clinical symptoms. Along with endoscopic mucosal healing, the long-term goal is to restore the quality of life and the absence of disability. The article discusses the use of drugs of the mesalazine group, topical and systemic steroids for the treatment of ulcerative colitis, as well as approaches to monitoring the disease and long-term management of patients.
About the Authors
A. M. KharitidisРоссия
Aleksandra M. Kharitidis, gastroenterologist
13 Dynamo Ave., St. Petersburg, 97110
O. B. Shchukina
Россия
Oksana B. Shchukina, Dr. of Sci. (Med.), Head of the office of inflammatory bowel diseases of the polyclinic with consultative and diagnostic center, Professor, Associate Professor of Department of General Medical Practice; Head
13 Dynamo Ave., St. Petersburg, 97110
6-8 Lev Tolstoy str., St. Petersburg, 197022
References
1. Kobayashi T., Siegmund B., LeBerre C., et al. Ulcerative colitis // Nat Rev Dis Prim. 2020; 6: 74.
2. Solberg I. C., Lygren I., Jahnsen J., et al. Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN study) // Scand J Gastroenterol. 2009; 44 (4): 431-440.
3. Farmer R. G., Easley K. A., Rankin G. B. Clinical patterns, natural history, and progression of ulcerative colitis. A long-term follow-up of 1116 patients // Dig. Dis. Sci. 1993; 38: 1137-1146.
4. Esaki M., Matsumoto T., Fuyuno Y. et al. Giant inflammatory polyposis of the cecum with repeated intussusception in ulcerative colitis: report of a case // Am. J. Gastroenterol. 2009; 104: 2873-2874.
5. Snape W. J. Jr. The role of a colonic motility disturbance in ulcerative colitis // Keio J. Med. 1991; 40: 6-8.
6. Peyrin-Biroulet L., Cieza A., Sandborn W. J. et al. for ulcerative colitis // N. Engl. J. Med. 2005; 353: 2462-2476.
7. Turner D., Ricciuto A., Lewis A., D’Amico F., Dhaliwal J., Griffiths A. M., et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD // Gastroenterology 2021. DOI: 10.1053/j.gastro.2020.12.031.
8. Leung C. M., Tang W., Kyaw M., Niamul G., Aniwan S., Limsrivilai J., et al. Endoscopic and histological mucosal healing in ulcerative colitis in the first year of diagnosis: Results from a population-based inception cohort from Six Countries in Asia // J Crohn’s Colitis 2017. DOI: 10.1093/ecco-jcc/jjx103.
9. Laharie D., Filippi J., Roblin X., Nancey S., Chevaux J. B., Hébuterne X., et al. Impact of mucosal healing on long-term outcomes in ulcerative colitis treated with infliximab: A multicenter experience // Aliment Pharmacol Ther. 2013. DOI: 10.1111/apt.12289.
10. Theede K., Kiszka-Kanowitz M., Nordgaard-Lassen I., Nielsen A. M. The impact of endoscopic inflammation and mucosal healing on health-related quality of life in ulcerative colitis patients // J Crohn’s Colitis. 2015. DOI: 10.1093/ecco-jcc/jjv081.
11. Magro F., Rodrigues A., Vieira A. I., et al. Review of the disease course among adult ulcerative colitis population-based longitudinal cohorts // Inflamm Bowel Dis. 2012; 18: 573-83. [PubMed] [Google Scholar].
12. Truelove S. C., Witts L. J. Cortisone in ulcerative colitis; final report on a therapeutic trial // Br Med J. 1955; 2: 1041-1048.
13. Silverberg M. S., Satsangi J., Ahmad T., Arnott I. D. R., Bernstein C. N., Brant S. R., et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology // Can J Gastroenterol. 2005. DOI: 10.1155/2005/269076.
14. Burisch J., Katsanos K. H., Christodoulou D. K., Barros L., Magro F., Pedersen N., et al. Natural Disease Course of Ulcerative Colitis during the First Five Years of Follow-up in a European Population-based Inception Cohort – An Epi-IBD Study // J Crohn’s Colitis 2019. DOI: 10.1093/ecco-jcc/jjy154.
15. Lee H. S., Park S. H., Yang S. K., Lee J., Soh J. S., Lee S., et al. Long-term prognosis of ulcerative colitis and its temporal change between 1977 and 2013: A hospital-based cohort study from Korea // J Crohn’s Colitis. 2015. DOI: 10.1093/ecco-jcc/jju017.
16. Fumery M., Singh S., Dulai P. S., Gower-Rousseau C., Peyrin-Biroulet L., Sandborn W.J. Natural History of Adult Ulcerative Colitis in Populationbased Cohorts: A Systematic Review // Clin Gastroenterol Hepatol. 2018; 16 (3): 343-356.
17. Sjöberg D., Holmström T., Larsson M., Nielsen A. L., Holmquist L., Ekbom A., et al. Incidence and clinical course of Crohn’s disease during the first year – results from the IBD Cohort of the Uppsala Region (ICURE) of Sweden 2005-2009 // Crohn’s Colitis. 2014; 8 (3): 215-222.
18. Reinisch W., Reinink A. R., Higgins P. D. R. Factors associated with poor outcomes in adults with newly diagnosed ulcerative colitis // Clin Gastroenterol Hepatol. 2015; 13: 635–642. [PubMed] [Google Scholar].
19. Etchevers M. J., Aceituno M., García-Bosch O., et al. Risk factors and characteristics of extent progression in ulcerative colitis // Inflamm Bowel Dis. 2009; 15: 1320-1325. [PubMed] [Google Scholar].
20. Barreiro-de Acosta M., Magro F., Carpio D., et al. Ulcerative colitis in Northern Portugal and Galicia in Spain // Inflamm Bowel Dis. 2010; 16: 1227-1238.
21. Choi C. H. R., Rutter M. D., Askari A., et al. Forty-year analysis of colonoscopic surveillance program for neoplasia in ulcerative colitis: an updated overview // Am J Gastroenterol. 2015; 110: 1022-1034. [PMC free article] [PubMed] [Google Scholar].
22. Beaugerie L., Itzkowitz S. H. Cancers complicating inflammatory bowel disease // N Engl J Med. 2015; 372: 1441-1452. [PubMed] [Google Scholar].
23. Frolkis A. D., Dykeman J., Negrón M. E., et al. Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies // Gastroenterology. 2013; 145: 996-1006. [PubMed] [Google Scholar].
24. 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: 483-489.
25. Arias M. T., VandeCasteele N., Vermeire S., et al. A panel to predict long-term outcome of infliximab therapy for patients with ulcerative colitis // Clin Gastroenterol Hepatol. 2015; 13: 531-538.
26. 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; 26 (317): 1625-1629.
27. Colombel J.-F., Keir M. E., Scherl A., et al. Discrepancies between patientreported outcomes, and endoscopic and histological appearance in UC // Gut. 2017; 66: 2063-2068.
28. Restellini S., Chao C. Y., Martel M., et al. Clinical parameters correlate with endoscopic activity of ulcerative colitis: a systematic review // Clin Gastroenterol Hepatol. 2019; 17: 1265-1275.
29. Harbord M., Eliakim R., Bettenworth D., et al. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: current management // J Crohns Colitis. 2017; 11 (7): 769-784.
30. Ko C. W., Singh S., Feuerstein J. D., et al. AGA clinical practice guidelines on the management of mild-to-moderate ulcerative colitis // Gastroenterology. 2019; 156 (3): 748-764.
31. Barreiro-de Acosta M., Vallejo N., de la Iglesia D., Uribarri L., Bastón I., Ferreiro-Iglesias R., Lorenzo A, Domínguez-Muñoz JE. 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: 13-19. PMID: 26351390. DOI: 10.1093/ecco-jcc/jjv158.
32. Boal Carvalho P., Dias de Castro F., Rosa B., Moreira M. J., Cotter J. Mucosal Healing in Ulcerative Colitis — When Zero is Better // J Crohns Colitis. 2016; 10: 20-25. PMID: 26438714. DOI: 10.1093/ecco-jcc/jjv180.
33. Mojtahed A., Khanna R., Sandborn W. J., et al. Assessment of histologic disease activity in Crohn’s disease: a systematic review // Inflamm Bowel Dis. 2014; 20: 2092-2103.
34. Bryant R. V., Burger D. C., 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: 408-414.
35. Zenlea T., Yee E. U., 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: 685-690.
36. Devlen J., Beusterien K., Yen L., et al. The burden of inflammatory bowel disease: a patient-reported qualitative analysis and development of a conceptual model // Inflamm Bowel Dis. 2014; 20: 545-552.
37. Drossman D. A., Patrick D. L., Mitchell C. M., et al. Health-related quality of life in inflammatory bowel disease. Functional status and patient worries and concerns // Dig Dis Sci. 1989; 34: 1379-1386.
38. Kappelman M. D., Long M. D., Martin C., et al. Evaluation of the patientreported outcomes measurement information system in a large cohort of patients with inflammatory bowel diseases // Clin Gastroenterol Hepatol. 2014; 12: 1315-1323.
39. Büsch K., Sonnenberg A., Bansback N. Impact of inflammatory bowel disease on disability // Curr Gastroenterol Rep. 2014; 16: 414.
40. Gauss A., Geib T., Hinz U., et al. Quality of life is related to fecal calprotectin concentrations in colonic crohn disease and ulcerative colitis, but not in ileal Crohn disease // Medicine (Baltimore). 2016; 95: e3477.
41. Allocca M., Fiorino G., Bonovas S., et al. Accuracy of humanitas ultrasound criteria in assessing disease activity and severity in ulcerative colitis: a prospective study // J Crohns Colitis. 2018; 12: 1385-1391.
42. Murray A., Nguyen T. M., Parker C. E., et al. Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis // Cochrane Database Syst Rev. 2020; 8: CD000543.
43. Ham M., Moss A. C. Mesalamine in the treatment and maintenance of remission of ulcerative colitis // Expert Rev Clin Pharmacol. 2012; 5 (2): 113-123.
44. Ye B. Mesalazine preparations for the treatment of ulcerative colitis: are all created equal? // World J Gastrointest Pharmacol Ther. 2015; 6 (4): 137.
45. Paridaens K., Fullarton J. R., Travis S. P. L. Efficacy and safety of oral Pentasa (prolonged-release mesalazine) in mild-to-moderate ulcerative colitis: a systematic review and meta-analysis. Pages 1891-1900. Received 24 Jul 2021, Accepted 12 Aug 2021, Accepted author version posted online: 18 Aug 2021, Published online: 01 Sep 2021.
46. Hanauer S., Schwartz J., Robinson M., et al. Mesalamine capsules for treatment of active ulcerative colitis: results of a controlled trial. Pentasa Study Group // Am J Gastroenterol. 1993; 88: 1188-1197.
47. Robinson M., Hanauer S., Hoop R., et al. Mesalamine capsules enhance the quality of life for patients with ulcerative colitis // Aliment PharmacolTher. 2007; 8 (1): 27-34.
48. Kane S. V. Systematic review: adherence issues in the treatment of ulcerative colitis // Aliment Pharmacol Ther. 2006; 23 (5): 577-585.
49. Flourie B., Hagege H., Tucat G., et al. Randomised clinical trial: once- vs. twice-daily prolonged-release mesalazine for active ulcerative colitis // Aliment Pharmacol Ther. 2013; 37 (8): 767-775.
50. Dignass A. U., Bokemeyer B., Adamek H., et al. Mesalamine once daily is more effective than twice daily in patients with quiescent ulcerative colitis // Clin Gastroenterol Hepatol. 2009; 7 (7): 762-769.
51. Raine T., Bonovas S. , Burisch J. et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment // Journal of Crohn's and Colitis, 2021, 1-16. https://doi.org/10.1093/ecco-jcc/jjab178 Advance Access publication October 12, 2021 ECCO Guideline/Consensus Paper.
52. Singh S., Feuerstein J. D., Binion D. G., Tremaine W. J. AGA technical review on the management of mild-to-moderate ulcerative colitis // Gastroenterology. 2019; 156: 769-808.
53. Barberio B., Segal J. P., Quraishi M. N., Black C. J., Savarinoa E. V., Ford A. C. Efficacy of Oral, Topical, or Combined Oral and Topical 5-Aminosalicylates, in Ulcerative Colitis: Systematic Review and Network Meta-analysis // Journal of Crohn's and Colitis. 2021, 1184-1196. DOI: 10.1093/ecco-jcc/jjab010.
54. Hartmann F., Stein J.; BudMesa-Study Group. Clinical trial: controlled, open, randomized multicentre study comparing the effects of treatment on quality of life, safety and efficacy of budesonide or mesalazine enemas in active left-sided ulcerative colitis // Aliment Pharmacol Ther. 2010; 32: 368-376.
55. Sandborn W. J., Travis S., Moro L., Jones R., Gautille T., Bagin R., et al. Once-daily budesonide MMX® extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: Results from the CORE i study // Gastroenterology. 2012. DOI: 10.1053/j.gastro.2012.08.003.
56. Travis S. P. L., Danese S., Kupcinskas L., Alexeeva O., D’Haens G., Gibson P. R., et al. Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: Results from the randomised CORE II study // Gut. 2014. DOI: 10.1136/gutjnl-2012-304258.
57. Therapeutic Goods Administration. Extract from the Clinical Evaluation Report for budesonide. Available at https://www.tga.gov.au/sites/default/files/auspar-budesonide160111-cer.pdf.
58. Ford A. C., Bernstein C. N., Khan K. J., et al. Glucocorticosteroid therapy in inflammatory bowel disease: Systematic review and meta-analysis // Am J Gastroenterol. 2011; 106: 590-599; quiz 600.
59. 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 metaregression // Clin Gastroenterol Hepatol. 2007; 5 (1): 103-110. DOI: 10.1016/j.cgh.2006.09.033.
60. Rubin D. T., Ananthakrishnan A. N., Siegel C. A., Sauer B. G., Long M. D. ACG Clinical Guideline: Ulcerative Colitis in Adults // Am J Gastroenterol. 2019; 114 (3): 384-413. DOI: 10.14309/ajg.0000000000000152.
61. Kornbluth A., Sachar D. B. Practice Parameters Committee of the American College of Gastroenterology Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee // Am J Gastroenterol. 2010; 105: 501-523. [PubMed] [Google Scholar].
62. Gower-Rousseau C., Sarter H., Savoye G., et al. the International Programme to Develop New Indexes for Crohn’s Disease (IPNIC) group, International Programme to Develop New Indexes for Crohn’s Disease IPNIC group Validation of the Inflammatory Bowel Disease Disability Index in a population-based cohort // Gut. 2015. Published online Dec 8. DOI: 10.1136/gutjnl-2015-310151. [PubMed] [CrossRef] [Google Scholar].
63. Bressler B., Marshall J. K., Bernstein C. N., et al. Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: the Toronto consensus // Gastroenterology. 2015; 148: 1035–58. [PubMed] [Google Scholar].
64. Peyrin-Biroulet L., Panes J., Sandborn W. J., et al. Defining disease severity in inflammatory bowel diseases: Current and future directions // Clin Gastroenterol Hepatol. 2015; 14: 348-354.
65. Sands B. E. Biomarkers of inflammation in inflammatory bowel disease // Gastroenterology. 2015; 149: 1275-1285.
66. Stragier E., Van Assche G. The use of fecal calprotectin and lactoferrin in patients with IBD. Review // Acta GastroEnterologica Belgica. 2013; 76: 322-328.
67. Canani R. B., Terrin G., Rapacciuolo L., et al. Faecal calprotectin as reliable non-invasive marker to assess the severity of mucosal inflammation in children with inflammatory bowel disease // Dig Liver Dis. 2008; 40: 547-553.
68. Schoepfer A. M., Beglinger C., Straumann A., et al. Ulcerative colitis: correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, Creactive protein, and blood leukocytes // Inflamm Bowel Dis. 2009; 15: 1851-1858.
69. Tibble J. A., Sigthorsson G., Bridger S., et al. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease // Gastroenterology. 2000; 119: 15-22.
70. Roszak D., Galecka M., Cichy W., et al. Determination of faecal inflammatory marker concentration as a noninvasive method of evaluation of pathological activity in April 2021 STRIDE-II 1581 CLINICAL AT children with inflammatory bowel diseases // Adv Med Sci. 2015; 60: 246-252.
71. Komraus M., Wos H., Wiecek S., et al. Usefulness of faecal calprotectin measurement in children with various types of inflammatory bowel disease // Mediators Inflamm. 2012; 2012: 608249.
72. Ashorn S., Honkanen T., Kolho K. L., et al. Fecal calprotectin levels and serological responses to microbial antigens among children and adolescents with inflammatory bowel disease // Inflamm Bowel Dis. 2009; 15: 199-205.
73. De Vos M., Dewit O., D’Haens G., et al. Fast and sharp decrease in calprotectin predicts remission by infliximab in anti-TNF naive patients with ulcerative colitis // J Crohns Colitis. 2012; 6: 557-562.
74. Ferreiro-Iglesias R., Barreiro-de Acosta M., Lorenzo Gonzalez A., et al. Accuracy of consecutive fecal calprotectin measurements to predict relapse in inflammatory bowel disease patients under maintenance with anti-TNF therapy: a prospective longitudinal cohort study // J Clin Gastroenterol. 2018; 52: 229-234.
75. Mak W. Y., Buisson A., Andersen M. J. Jr., et al. Fecal calprotectin in assessing endoscopic and histological remission in patients with ulcerative colitis // Dig Dis Sci. 2018; 63: 1294-1301.
Review
For citations:
Kharitidis A.M., Shchukina O.B. A modern view on the management of patients with ulcerative colitis of mild and moderate severity in outpatient practice. Lechaschi Vrach. 2022;(2):25-31. (In Russ.) https://doi.org/10.51793/OS.2022.25.2.004
JATS XML



















