lvrachЛечащий ВрачLechaschi Vrach1560-51752687-118110.51793/OS.2021.24.8.002lvrach-792Research ArticleГАСТРОЭНТЕРОЛОГИЯ. ГЕПАТОЛОГИЯGASTROENTEROLOGY. HEPATOLOGYОптимизация подходов к терапии язвенного колита легкой и средней степени тяжестиOptimization of approaches to the treatment of mild to moderate ulcerative colitisБелоусС. С.BelousS. S.

Москва

Moscow

КнязевО. В.KnyazevO. V.

доктор медицинских наук

Москва

Moscow

o.knyazev@mknc.ruФГБУ НМИЦ колопроктологии им. А. Н. Рыжих Минздрава РоссииРоссияRyzhikh National Medical Research Centre for Coloproctology of the Ministry of Health of the RussiaRussian FederationГБУЗ Московский КНЦ им. А. С. Логинова ДЗМРоссияMoscow Clinical Scientific Center n.a. A. S. LoginovRussian Federation202104092021081116Copyright © Белоус С.С., Князев О.В., 20212021Белоус С.С., Князев О.В.Belous S.S., Knyazev O.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.lvrach.ru/jour/article/view/792

Язвенный колит – аутоиммунное заболевание толстой кишки, проявляющееся развитием неспецифического воспаления его слизистой оболочки с обязательным поражением прямой кишки. Наиболее часто в клинической практике встречается левосторонний язвенный колит, легкая или среднетяжелая атака. Оптимальным способом лечения таких пациентов являются месалазины, однако применение препарата с рН-зависимой оболочкой может быть ограничено в связи с большим разнообразием значений рН у пациентов с воспалительными заболеваниями кишечника. Препаратами выбора в таких ситуациях являются покрытые этилцеллюлозой микрогранулы месалазина с пролонгированным высвобождением, позволяющие достигнуть максимального терапевтического эффекта. Для улучшения результатов терапии месалазинами необходимо комбинированное применение местного и системного препарата. При неэффективности данного подхода в качестве альтернативы системным глюкокортикостероидам можно рассмотреть вопрос о назначении будесонида ММХ с новой мультиматриксной системой высвобождения месалазина (multimatrix system, ММХ).

Ulcerative colitis is an autoimmune disease of the colon, manifested by the development of non-specific inflammation of its mucous membrane with a mandatory lesion of the rectum. The most common in clinical practice is left-sided ulcerative colitis, a mild or moderate attack. The optimal treatment for such patients is mesalazine, but the use of the drug with a pH-dependent shell may be limited due to the large variety of pH values in patients with inflammatory bowel diseases. The drugs of choice in such situations are ethylcellulose-coated mesalazine microgranules with prolonged release, which allow to achieve the maximum therapeutic effect. To improve the results of mesalazine therapy, the combined use of a local and systemic drug is necessary. If this approach is ineffective, the use of budesonide MMH may be considered as an alternative to systemic glucocorticosteroids.

месалазинсхема лечениятерапияязвенный колитпроктитлевостороннее поражениебудесонидсуппозиториисистема доставкиММХmesalazinetreatment schemetherapyulcerative colitisproctitisleft-side colitisbudesonidesuppositoriadelivery systemMMXReferencesUngaro R., Mehandru S., Allen P. B., Peyrin-Biroulet L., Colombel J. F. Ulcerative colitis // Lancet. 2017; 389: 1756-1770.Ungaro R., Mehandru S., Allen P. B., Peyrin-Biroulet L., Colombel J. F. Ulcerative colitis // Lancet. 2017; 389: 1756-1770.Roda G., Narula N., Pinotti R., Skamnelos A., Katsanos K. H., Ungaro R., Burisch J., Torres J., Colombel J. F. Systematic review with meta-analysis: Proximal disease extension in limited ulcerative colitis // Aliment. Pharmacol. Ther. 2017; 45: 1481-1492.Roda G., Narula N., Pinotti R., Skamnelos A., Katsanos K. H., Ungaro R., Burisch J., Torres J., Colombel J. F. Systematic review with meta-analysis: Proximal disease extension in limited ulcerative colitis // Aliment. Pharmacol. Ther. 2017; 45: 1481-1492.Reinisch W., Sandborn W. J., Bala M., Yan S., Feagan B. G., Rutgeerts P., Radford-Smith G., Xu S., Eisenberg D., Olson A., et al. Response and remission are associated with improved quality of life, employment and disability status, hours worked, and productivity of patients with ulcerative colitis // Inflamm Bowel Dis. 2007; 13: 1135-1140.Reinisch W., Sandborn W. J., Bala M., Yan S., Feagan B. G., Rutgeerts P., Radford-Smith G., Xu S., Eisenberg D., Olson A., et al. Response and remission are associated with improved quality of life, employment and disability status, hours worked, and productivity of patients with ulcerative colitis // Inflamm Bowel Dis. 2007; 13: 1135-1140.Ramos A., Calvet X., Sicilia B., Vergara M., Figuerola A., Motos J., Sastre A., Villoria A., Gomollón F. IBD-related work disability in the community: Prevalence, severity and predictive factors. A cross-sectional study // United Eur. Gastroenterol. J. 2015; 3: 335-342.Ramos A., Calvet X., Sicilia B., Vergara M., Figuerola A., Motos J., Sastre A., Villoria A., Gomollón F. IBD-related work disability in the community: Prevalence, severity and predictive factors. A cross-sectional study // United Eur. Gastroenterol. J. 2015; 3: 335-342.Yashiroм M. Ulcerative colitis-associated colorectal cancer // World J. Gastroenterol. 2014; 20: 16389-16397.Yashiroм M. Ulcerative colitis-associated colorectal cancer // World J. Gastroenterol. 2014; 20: 16389-16397.Magro F., Gionchetti P., Eliakim R., Ardizzone S., Armuzzi A., Barreiro-de Acosta M., Burisch J., Gecse K. B., Hart A. L., Hindryckx P., et al. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: Definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders // J. Crohn’s Colitis. 2017; 11: 649-670.Magro F., Gionchetti P., Eliakim R., Ardizzone S., Armuzzi A., Barreiro-de Acosta M., Burisch J., Gecse K. B., Hart A. L., Hindryckx P., et al. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: Definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders // J. Crohn’s Colitis. 2017; 11: 649-670.Silverberg M. S., Satsangi J., Ahmad T., ArnottI D. R., Bernstein C. N., Brant S. R., Caprilli R., Colombel J. F., Gasche C., Geboes K., 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; 19 [Suppl. A]: 5A-36A.Silverberg M. S., Satsangi J., Ahmad T., ArnottI D. R., Bernstein C. N., Brant S. R., Caprilli R., Colombel J. F., Gasche C., Geboes K., 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; 19 [Suppl. A]: 5A-36A.Satsangi J., Silverberg M. S., Vermeire S., Colombel J. F. The Montreal classification of inflammatory bowel disease: Controversies, consensus, and implications // Gut. 2006; 55; 749-753.Satsangi J., Silverberg M. S., Vermeire S., Colombel J. F. The Montreal classification of inflammatory bowel disease: Controversies, consensus, and implications // Gut. 2006; 55; 749-753.Truelove S. C., Witts L. J. Cortisone in ulcerative colitis // BMJ. 1955.Truelove S. C., Witts L. J. Cortisone in ulcerative colitis // BMJ. 1955.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: 343-356.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: 343-356.Harbord M., Eliakim R., Bettenworth D., Karmiris K., Katsanos K., Kopylov U., Kucharzik T., Molnár T., Raine T., Sebastian S., et al. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: Current management // J. Crohn’s Colitis. 2017; 11: 769-784.Harbord M., Eliakim R., Bettenworth D., Karmiris K., Katsanos K., Kopylov U., Kucharzik T., Molnár T., Raine T., Sebastian S., et al. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 2: Current management // J. Crohn’s Colitis. 2017; 11: 769-784.De Cassan C., Fiorino G., Danese S. Second-generation corticosteroids for the treatment of Crohn’s disease and ulcerative colitis: More effective and less side effects? // Dig. Dis. 2012; 30: 368-375.De Cassan C., Fiorino G., Danese S. Second-generation corticosteroids for the treatment of Crohn’s disease and ulcerative colitis: More effective and less side effects? // Dig. Dis. 2012; 30: 368-375.Danese S., Roda G., Peyrin-Biroulet L. Evolving therapeutic goals in ulcerative colitis: Towards disease clearance // Nat. Rev. Gastroenterol. Hepatol. 2020; 17: 1-2.Danese S., Roda G., Peyrin-Biroulet L. Evolving therapeutic goals in ulcerative colitis: Towards disease clearance // Nat. Rev. Gastroenterol. Hepatol. 2020; 17: 1-2.Nguyen N. H., Fumery M., Dulai P. S., Prokop L. J., Sandborn W. J., Murad M. H., Singh S. Comparative efficacy and tolerability of pharmacological agents for management of mild to moderate ulcerative colitis: A systematic review and network meta-analyses // Lancet Gastroenterol. Hepatol. 2018; 3: 742-753.Nguyen N. H., Fumery M., Dulai P. S., Prokop L. J., Sandborn W. J., Murad M. H., Singh S. Comparative efficacy and tolerability of pharmacological agents for management of mild to moderate ulcerative colitis: A systematic review and network meta-analyses // Lancet Gastroenterol. Hepatol. 2018; 3: 742-753.Ивашкин В. Т., Шелыгин Ю. А., Белоусова Е. А., Абдулганиева Д. И., Алексеева О. А., Ачкасов С. И., Валуйских Е. Ю., Варданян А. В., Веселов А. В., Веселов В. В., Головенко О. В., Губонина И. В., Жигалова Т. Н., Кашников В. Н., Князев О. В., Макарчук П. А., Москалев А. И., Нанаева Б. А., Низов А. А., Никитина Н. В., Николаева Н. Н., Павленко В. В., Полуэктова Е. А., Светлова И. О., Тарасова Л. В., Ткачев А. В., Фролов С. А., Хлынова О. В., Чашкова Е. Ю., Шапина М. В., Шептулин А. А., Шифрин О. С., Щукина О. Б. Проект клинических рекомендаций по диагностике и лечению язвенного колита // Колопроктология. 2019; 18; 4: 7-36.Ivashkin V. T., Shelygin Yu. A., Belousova Ye. A., Abdulganiyeva D. I., Alekseyeva O. A., Achkasov S. I., Valuyskikh Ye. Yu., Vardanyan A. V., Veselov A. V., Veselov V. V., Golovenko O. V., Gubonina I. V., Zhigalova T. N., Kashnikov V. N., Knyazev O. V., Makarchuk P. A., Moskalev A. I., Nanayeva B. A., Nizov A. A., Nikitina N. V., Nikolayeva N. N., Pavlenko V. V., Poluektova Ye. A., Svetlova I. O., Tarasova L. V., Tkachev A. V., Frolov S. A., Khlynova O. V., Chashkova Ye. Yu., Shapina M. V., Sheptulin A. A., Shifrin O. S., Shchukina O. B. Proyekt klinicheskikh rekomendatsiy po diagnostike i lecheniyu yazvennogo kolita [Draft clinical guidelines on the diagnosis and treatment of ulcerative colitis] Koloproktologiya. 2019; 18; 4: 7-36.Lamet M. A multicenter, randomized study to evaluate the efficacy and safety of mesalamine suppositories 1 g at bedtime and 500 mg twice daily in patients with active mild-to-moderate ulcerative proctitis // Dig Dis Sci. 2011; 56: 513-22.Lamet M. A multicenter, randomized study to evaluate the efficacy and safety of mesalamine suppositories 1 g at bedtime and 500 mg twice daily in patients with active mild-to-moderate ulcerative proctitis // Dig Dis Sci. 2011; 56: 513-22.Sutherland L., Macdonald J. K. Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis // Cochrane Database Syst Rev. 2006; CD000543.Sutherland L., Macdonald J. K. Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis // Cochrane Database Syst Rev. 2006; CD000543.Regueiro M., Loftus Jr. E. V., Steinhart A. H., Cohen R. D. Medical management of left-sided ulcerative colitis and ulcerative proctitis: critical evaluation of therapeutic trials // Inflamm Bowel Dis. 2006; 12: 979-994.Regueiro M., Loftus Jr. E. V., Steinhart A. H., Cohen R. D. Medical management of left-sided ulcerative colitis and ulcerative proctitis: critical evaluation of therapeutic trials // Inflamm Bowel Dis. 2006; 12: 979-994.Ford A. C., Achkar J.-P., Khan K. J., Kane S. V., Talley N. J., et al. Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and metaanalysis // Am J Gastroenterol. 2011; 106: 601-616.Ford A. C., Achkar J.-P., Khan K. J., Kane S. V., Talley N. J., et al. Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and metaanalysis // Am J Gastroenterol. 2011; 106: 601-616.Ford A. C., Khan K. J., Achkar J. P., et al. Efficacy of oral vs. topical, or combined oral and topical 5-aminosalicylates, in Ulcerative Colitis: systematic review and meta-analysis // The American journal of gastroenterology. 2012; 107: 167-176.Ford A. C., Khan K. J., Achkar J. P., et al. Efficacy of oral vs. topical, or combined oral and topical 5-aminosalicylates, in Ulcerative Colitis: systematic review and meta-analysis // The American journal of gastroenterology. 2012; 107: 167-176.Kane S. V., Bjorkman D. J. The efficacy of oral 5-ASAs in the treatment of active ulcerative colitis: a systematic review // Rev Gastroenterol Disord. 2003; 3: 210-218.Kane S. V., Bjorkman D. J. The efficacy of oral 5-ASAs in the treatment of active ulcerative colitis: a systematic review // Rev Gastroenterol Disord. 2003; 3: 210-218.Feagan B. G., MacDonald J. K. Oral5-aminosalicylic acid for induction of remission in ulcerative colitis // Cochrane Database Syst Rev. 2012; 10: CD000543.Feagan B. G., MacDonald J. K. Oral5-aminosalicylic acid for induction of remission in ulcerative colitis // Cochrane Database Syst Rev. 2012; 10: CD000543.Feagan B. G., MacDonald J. K. Oral5-aminosalicylic acid for maintenance of remission in ulcerative colitis // Cochrane Database Syst Rev. 2012; 10: CD000544.Feagan B. G., MacDonald J. K. Oral5-aminosalicylic acid for maintenance of remission in ulcerative colitis // Cochrane Database Syst Rev. 2012; 10: CD000544.Raimundo A. N., Evans D. F., Rogers J. et al. Intestinal pH in ulcerative colitis: acute [untreated] and in remission on 5-aminosalicylic acid [5-ASA] // Gut. 1992; 33; 1: S63.Raimundo A. N., Evans D. F., Rogers J. et al. Intestinal pH in ulcerative colitis: acute [untreated] and in remission on 5-aminosalicylic acid [5-ASA] // Gut. 1992; 33; 1: S63.De Vos M., Verdievel H., Achoonjns R. et al. Concentration of 5-ASA and Ac-5-ASA in human ileocolonic biopsy homogenates after oral 5-ASA preparations // Gut. 1992; 33: 1338-1342.De Vos M., Verdievel H., Achoonjns R. et al. Concentration of 5-ASA and Ac-5-ASA in human ileocolonic biopsy homogenates after oral 5-ASA preparations // Gut. 1992; 33: 1338-1342.Hanauer S. B. Inflammatoryboweldisease // NEnglJMed. 1996; 334: 841-848.Hanauer S. B. Inflammatoryboweldisease // NEnglJMed. 1996; 334: 841-848.Yu D. K., Morrill B., Eichmeier L. S., et al. Pharmacokinetics of 5-aminosalicylic acid from controlled-release capsules in man // Eur J Clin Pharmacol. 1995; 48: 273-277.Yu D. K., Morrill B., Eichmeier L. S., et al. Pharmacokinetics of 5-aminosalicylic acid from controlled-release capsules in man // Eur J Clin Pharmacol. 1995; 48: 273-277.Wilding I. R., Kenyon C. J., Hooper G. Gastrointestinal spread of oral prolonged-release mesalazine microgranules [Pentasa] dosed as either tablets or sachet // Aliment Pharmacol Ther. 2000; 14: 163-169.Wilding I. R., Kenyon C. J., Hooper G. Gastrointestinal spread of oral prolonged-release mesalazine microgranules [Pentasa] dosed as either tablets or sachet // Aliment Pharmacol Ther. 2000; 14: 163-169.Small R. E., Schraa C. C. Chemistry, pharmacology, pharmacokinetics, and clinical applications of mesalamine for the treatmentofinflammatoryboweldi sease // Pharmacotherapy. 1994; 14: 385-398.Small R. E., Schraa C. C. Chemistry, pharmacology, pharmacokinetics, and clinical applications of mesalamine for the treatmentofinflammatoryboweldi sease // Pharmacotherapy. 1994; 14: 385-398.Rasmussen S. N., Bondesen S., Hvidberg E. F., et al. 5-Aminosalicylicacidinaslow-releasepreparation:bioavailability, plasma level, and excretion in humans // Gastroenterology. 1982; 83: 1062-1070.Rasmussen S. N., Bondesen S., Hvidberg E. F., et al. 5-Aminosalicylicacidinaslow-releasepreparation:bioavailability, plasma level, and excretion in humans // Gastroenterology. 1982; 83: 1062-1070.Stolk L. M., Rietbroek R., Wiltink E. H., et al. Dissolution profiles of mesalazine for mulations in vitro // Pharm Weekbl Sci. 1990; 12: 200-204.Stolk L. M., Rietbroek R., Wiltink E. H., et al. Dissolution profiles of mesalazine for mulations in vitro // Pharm Weekbl Sci. 1990; 12: 200-204.Dignass A., Lindsay J. O., Sturm A., et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis: current management // J Crohns Colitis. 2012; 6: 991-1030.Dignass A., Lindsay J. O., Sturm A., et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis: current management // J Crohns Colitis. 2012; 6: 991-1030.Kornbluth A., Sachar D. V. Ulcerative colitis practice guidelines in adults. American College of Gastroenterology, Practice Parameters Committee // Am J Gastroenterol. 2010; 105; 501-523.Kornbluth A., Sachar D. V. Ulcerative colitis practice guidelines in adults. American College of Gastroenterology, Practice Parameters Committee // Am J Gastroenterol. 2010; 105; 501-523.Campieri M., Corbelli C., Gionchetti P., et al. Spread and distribution of 5-ASA colonic foam and 5-ASA enemas in patients with ulcerative colitis // Dig Dis Sci. 1992; 37: 1890-1897.Campieri M., Corbelli C., Gionchetti P., et al. Spread and distribution of 5-ASA colonic foam and 5-ASA enemas in patients with ulcerative colitis // Dig Dis Sci. 1992; 37: 1890-1897.Chapman N. J., Brawn M. L., Phillips S. F., et al. Distribution of mesalamine enemas in patients with active distal ulcerative colitis //Mayo Clin Proc. 1992; 67: 245-248.Chapman N. J., Brawn M. L., Phillips S. F., et al. Distribution of mesalamine enemas in patients with active distal ulcerative colitis //Mayo Clin Proc. 1992; 67: 245-248.Nymann-Pantelidis M., Nilsson A., Wagner Z. G., Borga O. Pharmacokinetics and retrograde colonic spread of budesonide enemas in patients with distal colitis // Aliment Pharmacol Ther. 1994; 8: 617-622.Nymann-Pantelidis M., Nilsson A., Wagner Z. G., Borga O. Pharmacokinetics and retrograde colonic spread of budesonide enemas in patients with distal colitis // Aliment Pharmacol Ther. 1994; 8: 617-622.Brown J., Haines S., Wilding I. R. Colonic spread of three rectally administered mesalazine [Pentasa] dosage forms in healthy volunteers as assessed by gamma scintigraphy // Aliment Pharmacol Ther. 1997; 11: 685-691.Brown J., Haines S., Wilding I. R. Colonic spread of three rectally administered mesalazine [Pentasa] dosage forms in healthy volunteers as assessed by gamma scintigraphy // Aliment Pharmacol Ther. 1997; 11: 685-691.Wilding I. K., Kenyan C. J., Chauhan S. et al. Colonic spreading of a nonchlorafluorocarnon mesalazine rectal foam enema in patients with quiescent ulcerative colitis // Aliment Pharmacol Ther. 1995; 9: 161-166.Wilding I. K., Kenyan C. J., Chauhan S. et al. Colonic spreading of a nonchlorafluorocarnon mesalazine rectal foam enema in patients with quiescent ulcerative colitis // Aliment Pharmacol Ther. 1995; 9: 161-166.Van Bodegraven A. A., Boer R. O., Lourens J., et al. Distribution of mesalazine enemas in active and quiescent ulcerative colitis // Aliment Pharmacol Ther. 1996; 10: 327-332.Van Bodegraven A. A., Boer R. O., Lourens J., et al. Distribution of mesalazine enemas in active and quiescent ulcerative colitis // Aliment Pharmacol Ther. 1996; 10: 327-332.Williams C. N., Haber G., Aquino J. A. Double-blind, placebocontrolled evaluation of 5-ASA suppositories in active distal proctitis and measurement of extent of spread using 99mTc -labelles 5-ASA suppositories // Dis Sci. 1987; 32: 71-75.Williams C. N., Haber G., Aquino J. A. Double-blind, placebocontrolled evaluation of 5-ASA suppositories in active distal proctitis and measurement of extent of spread using 99mTc -labelles 5-ASA suppositories // Dis Sci. 1987; 32: 71-75.Munakata A., Yoshida Y., MutoT., et al. Double-blind comparative study of sulfasalazine and controlled-release mesalazine tablets in the treatment of active ulcerative colitis // J Gastroenterol. 1995; 30 Suppl. 8: 108-111.Munakata A., Yoshida Y., MutoT., et al. Double-blind comparative study of sulfasalazine and controlled-release mesalazine tablets in the treatment of active ulcerative colitis // J Gastroenterol. 1995; 30 Suppl. 8: 108-111.Farup P. G., Oddsson E., Hinterleitner T. Mesalamine 4 g prolonged release granules b.i.d. and q.i.d. versus tablets q.i.d. formild/moderateulcerativecolitis[abstract] // Gastroenterology. 1999; 116 (2): A713.Farup P. G., Oddsson E., Hinterleitner T. Mesalamine 4 g prolonged release granules b.i.d. and q.i.d. versus tablets q.i.d. formild/moderateulcerativecolitis[abstract] // Gastroenterology. 1999; 116 (2): A713.Fockens P., Mulder C. J. J., Tytgat G. N. J., et al. Comparison of the efficacy and safety of 1.5 compared with 3.0 g oral slow-release mesalazine [Pentasa] in the maintenance treatment of ulcerativecolitis // Eur J Gastroenterol Hepatol. 1995; 7: 1025-1030.Fockens P., Mulder C. J. J., Tytgat G. N. J., et al. Comparison of the efficacy and safety of 1.5 compared with 3.0 g oral slow-release mesalazine [Pentasa] in the maintenance treatment of ulcerativecolitis // Eur J Gastroenterol Hepatol. 1995; 7: 1025-1030.Mulder C. J., Tytgat G. N. J., Weterman I. T., et al. Double-blindcomparison of slow-release 5-aminosalicylate and sulfasalazine in remission maintenance in ulcerative colitis // Gastroenterology. 1988; 95: 1449-1453.Mulder C. J., Tytgat G. N. J., Weterman I. T., et al. Double-blindcomparison of slow-release 5-aminosalicylate and sulfasalazine in remission maintenance in ulcerative colitis // Gastroenterology. 1988; 95: 1449-1453.Miner P., Hanauer S., Robinson M., et al. Safety and efficacy of controlledrelease mesalamine for maintenance of remission inulcerativecolitis // Dig Dis Sci. 1995; 40: 296-304.Miner P., Hanauer S., Robinson M., et al. Safety and efficacy of controlledrelease mesalamine for maintenance of remission inulcerativecolitis // Dig Dis Sci. 1995; 40: 296-304.Hanauer S. B., Sandborn W. J., Kornbluth A., Katz S., Safdi M., Woogen S., Regalli G., Yeh C., Smith-Hall N., Ajayi F. Delayed-release oral mesalamine at 4.8 g/day [800 mg tablet] for the treatment of moderately active ulcerative colitis: The ASCEND II trial // Am. J. Gastroenterol. 2005; 100: 2478-2485.Hanauer S. B., Sandborn W. J., Kornbluth A., Katz S., Safdi M., Woogen S., Regalli G., Yeh C., Smith-Hall N., Ajayi F. Delayed-release oral mesalamine at 4.8 g/day [800 mg tablet] for the treatment of moderately active ulcerative colitis: The ASCEND II trial // Am. J. Gastroenterol. 2005; 100: 2478-2485.Angelucci E., Malesci A., DaneseS. Budesonide: Teaching an old dog new tricks for inflammatory Bowel disease treatment // Curr. Med. Chem. 2008; 15: 2527-2535.Angelucci E., Malesci A., DaneseS. Budesonide: Teaching an old dog new tricks for inflammatory Bowel disease treatment // Curr. Med. Chem. 2008; 15: 2527-2535.Hoy S. M. BudesonideMMX ® : A review of its use in patients with mild to moderate ulcerative colitis // Drugs. 2015; 75: 879-886.Hoy S. M. BudesonideMMX ® : A review of its use in patients with mild to moderate ulcerative colitis // Drugs. 2015; 75: 879-886.Sandborn W. J., TravisS., Moro L., Jones R., Gautille T., Bagin R., Huang M., Yeung P., Ballard E. D. Once-daily budesonide MMX ® extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: Results from the COREI study // Gastroenterology. 2012; 143: 1218-1226.Sandborn W. J., TravisS., Moro L., Jones R., Gautille T., Bagin R., Huang M., Yeung P., Ballard E. D. Once-daily budesonide MMX ® extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: Results from the COREI study // Gastroenterology. 2012; 143: 1218-1226.Travis S. P. L., Danese S., Kupcinskas L., Alexeeva O., D’Haens G., Gibson P. R., Moro L., Jones R., Ballard E. D., Masure J., et al. Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: Results from the randomised CORE II study // Gut. 2014; 63: 433-441.Travis S. P. L., Danese S., Kupcinskas L., Alexeeva O., D’Haens G., Gibson P. R., Moro L., Jones R., Ballard E. D., Masure J., et al. Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: Results from the randomised CORE II study // Gut. 2014; 63: 433-441.Sandborn W. J., Danese S., D’Haens G., Moro L., Jones R., Bagin R., Huang M., David Ballard E., Masure J., Travis S. Induction of clinical and colonoscopic remission of mild-to-moderate ulcerative colitis with budesonide MMX 9 mg: Pooled analysis of two phase 3 studies // Aliment. Pharmacol. Ther. 2015; 41: 409-418.Sandborn W. J., Danese S., D’Haens G., Moro L., Jones R., Bagin R., Huang M., David Ballard E., Masure J., Travis S. Induction of clinical and colonoscopic remission of mild-to-moderate ulcerative colitis with budesonide MMX 9 mg: Pooled analysis of two phase 3 studies // Aliment. Pharmacol. Ther. 2015; 41: 409-418.Lichtenstein G. R., Travis S., Danese S., D’Haens G., Moro L., Jones R., Huang M., Ballard E. D., Bagin R., HardimanY., et al. Budesonide MMX for the induction of remission of mild to moderate ulcerative colitis: A pooled safety analysis // J. Crohn’s. Colitis. 2015; 9: 738-746.Lichtenstein G. R., Travis S., Danese S., D’Haens G., Moro L., Jones R., Huang M., Ballard E. D., Bagin R., HardimanY., et al. Budesonide MMX for the induction of remission of mild to moderate ulcerative colitis: A pooled safety analysis // J. Crohn’s. Colitis. 2015; 9: 738-746.Rubin D. T., Cohen R. D., Sandborn W. J., Lichtenstein G. R., Axler J., Riddell R. H.. Zhu C., Barrett A. C., Bortey E., Forbes W. P. Budesonide multimatrix is efficacious for mesalamine-refractory, mild to moderate ulcerative colitis: A randomised, placebo-controlled trial // J. Crohn’s Colitis. 2017; 11: 785-791.Rubin D. T., Cohen R. D., Sandborn W. J., Lichtenstein G. R., Axler J., Riddell R. H.. Zhu C., Barrett A. C., Bortey E., Forbes W. P. Budesonide multimatrix is efficacious for mesalamine-refractory, mild to moderate ulcerative colitis: A randomised, placebo-controlled trial // J. Crohn’s Colitis. 2017; 11: 785-791.Bonovas S., Nikolopoulos G. K., Piovani D., González-Lorenzo M., Pantavou K., Lytras T., Peyrin-Biroulet L., Danese S. Comparative assessment of budesonide-MMX and mesalamine in active, mild-to-moderate ulcerative colitis: A systematic review and network meta-analysis // Br. J. Clin. Pharmacol. 2019; 85: 2244-2254.Bonovas S., Nikolopoulos G. K., Piovani D., González-Lorenzo M., Pantavou K., Lytras T., Peyrin-Biroulet L., Danese S. Comparative assessment of budesonide-MMX and mesalamine in active, mild-to-moderate ulcerative colitis: A systematic review and network meta-analysis // Br. J. Clin. Pharmacol. 2019; 85: 2244-2254.Maconi G., Mezzina N., Landi S., Grillo S., Bezzio C., Bosani M., Pastorelli L., Dell’Era A., Chibbar R., Carmagnola S., et al. Use, effectiveness and tolerability of budesonide-MMX in ulcerative colitis: A real-life experience // United Eur. Gastroenterol. J. 2019; 7: 1164-1170.Maconi G., Mezzina N., Landi S., Grillo S., Bezzio C., Bosani M., Pastorelli L., Dell’Era A., Chibbar R., Carmagnola S., et al. Use, effectiveness and tolerability of budesonide-MMX in ulcerative colitis: A real-life experience // United Eur. Gastroenterol. J. 2019; 7: 1164-1170.Danese S., Hart A., Dignass A., Fiorino G., Louis E., Bonovas S., D’Haens G., Dotan I., Rogler G., Paridaens K., et al. A multicentre prospective cohort study assessing the effectiveness of budesonide MMX ® [CortimentMMX ® ] for active, mild-to-moderate ulcerative colitis // United Eur. Gastroenterol. J. 2019; 7: 1171-1182.Danese S., Hart A., Dignass A., Fiorino G., Louis E., Bonovas S., D’Haens G., Dotan I., Rogler G., Paridaens K., et al. A multicentre prospective cohort study assessing the effectiveness of budesonide MMX ® [CortimentMMX ® ] for active, mild-to-moderate ulcerative colitis // United Eur. Gastroenterol. J. 2019; 7: 1171-1182.Magro F., Estevinho M. M. Moving from efficacy to effectiveness: Budesonide multimatrix in ulcerative colitis // United Eur. Gastroenterol. J. 2019; 7: 1153-1155.Magro F., Estevinho M. M. Moving from efficacy to effectiveness: Budesonide multimatrix in ulcerative colitis // United Eur. Gastroenterol. J. 2019; 7: 1153-1155.Ko C. W., Singh S., Feuerstein J. D., Falck-Ytter C., Falck-Ytter Y., Cross R. K., Crockett S., Feuerstein J., Flamm S., Inadomi J., et al. AGA clinical practice guidelines on the management of mild-to-moderate ulcerative colitis // Gastroenterology. 2019; 156: 748-764.Ko C. W., Singh S., Feuerstein J. D., Falck-Ytter C., Falck-Ytter Y., Cross R. K., Crockett S., Feuerstein J., Flamm S., Inadomi J., et al. AGA clinical practice guidelines on the management of mild-to-moderate ulcerative colitis // Gastroenterology. 2019; 156: 748-764.Williams C. N. Clinical experience with 5-amino-salicylate preparations in inflammatory bowel disease-a review // Can J Gastroenterol. 1987; 1: 28-32.Williams C. N. Clinical experience with 5-amino-salicylate preparations in inflammatory bowel disease-a review // Can J Gastroenterol. 1987; 1: 28-32.Malatjalian D. A., Williams C. N. 5-ASA therapy in the solitary rectal ulcer syndrome. Report of three patients // Can J Gastroenterol. 1988; 2: 18-21.Malatjalian D. A., Williams C. N. 5-ASA therapy in the solitary rectal ulcer syndrome. Report of three patients // Can J Gastroenterol. 1988; 2: 18-21.Klotz U., et al. Therapeutic efficacy of sulfasalazine and its metabolites in patients with ulcerative colitis and Crohn’s disease // N Engl J Med. 1980; 303: 1499.Klotz U., et al. Therapeutic efficacy of sulfasalazine and its metabolites in patients with ulcerative colitis and Crohn’s disease // N Engl J Med. 1980; 303: 1499.Van Hees P. A. M., et al. Active therapeutic moiety of sulphasalazine [letter] // Lancet. 1978; 1: 277.Van Hees P. A. M., et al. Active therapeutic moiety of sulphasalazine [letter] // Lancet. 1978; 1: 277.Maier K., et al. Colitis ulcerosa. Prufung eines neu entwickelten Aktivitatsindex im Rahmen einer Therapiestudie mit Mesalazin // Fortschr Med. 1987; 105: 61-65.Maier K., et al. Colitis ulcerosa. Prufung eines neu entwickelten Aktivitatsindex im Rahmen einer Therapiestudie mit Mesalazin // Fortschr Med. 1987; 105: 61-65.Campieri M., et al. 2nd International Conference-Trends in IBD Therapy. Alberta, Canada, April, 1988.Campieri M., et al. 2nd International Conference-Trends in IBD Therapy. Alberta, Canada, April, 1988.Clemett D., Markham A. Prolonged-release mesalazine: a review of its therapeutic potential in ulcerative colitis and Crohn's disease // Drugs. 2000; 59; 4: 929-956.Clemett D., Markham A. Prolonged-release mesalazine: a review of its therapeutic potential in ulcerative colitis and Crohn's disease // Drugs. 2000; 59; 4: 929-956.Ford A. C., Achkar J. P., Khan K. J., et al. Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and meta-analysis // Am J Gastroenterol. 2011; 106: 601-616.Ford A. C., Achkar J. P., Khan K. J., et al. Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and meta-analysis // Am J Gastroenterol. 2011; 106: 601-616.

The authors declare that there are no conflicts of interest present.