gnckКолопроктологияKoloproktologia2073-75562686-7303Russian Association of Coloproctology10.33878/2073-7556-2021-20-3-43-50gnck-1653Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESЭффективность тофацитиниба в качестве «терапии спасения» у пациентов с язвенным колитом тяжелой степениEfficacy of tofacitinib as a «rescue therapy» in patients with severe ulcerative colitishttps://orcid.org/0000-0001-5694-1051ПодольскаяД. В.PodolskayaD. V.

Подольская Д.В.

ул. Саляма Адиля, д. 2, г. Москва, 123423

Darya V. Podolskaya

Salyama Adilya str., 2, Moscow, 123423

https://orcid.org/0000-0003-1172-6221ШапинаМ. В.ShapinaM. V.

Шапина М.В.

ул. Саляма Адиля, д. 2, г. Москва, 123423

Marina V. Shapina

Salyama Adilya str., 2, Moscow, 123423

https://orcid.org/0000-0003-2013-8798БарановаТ. А.BaranovaT. A.

Баранова Т.А.

ул. Саляма Адиля, д. 2, г. Москва, 123423

Tatyana A. Baranova

Salyama Adilya str., 2, Moscow, 123423

ТишаеваИ. А.TishaevaI. A.

Тишаева И.А.

ул. Саляма Адиля, д. 2, г. Москва, 123423

Irina A. Tishaeva

Salyama Adilya str., 2, Moscow, 123423

https://orcid.org/0000-0002-8803-7566АлександровТ. Л.AlexandrovT. L.

Александров Т.Л.

ул. Саляма Адиля, д. 2, г. Москва, 123423

Timofey L. Alexandrov

Salyama Adilya str., 2, Moscow, 123423

https://orcid.org/0000-0001-7250-0977КнязевО. В.KnyazevO. V.

Князев О.В.

ул. Саляма Адиля, д. 2, г. Москва, 123423

ул. шоссе Энтузиастов, д. 86, г. Москва, 111123

 

Oleg V. Knyazev

Salyama Adilya str., 2, Moscow, 123423

shosse Entusiastov, 86, Moscow, 111123

https://orcid.org/0000-0003-1697-4670НанаеваБ. А.NanaevaB. A.

Нанаева Б.А.

ул. Саляма Адиля, д. 2, г. Москва, 123423

Bella A. Nanaeva

Salyama Adilya str., 2, Moscow, 123423

ФГБУ «НМИЦ колопроктологии имени А.Н. Рыжих» Минздрава РоссииРоссияRyzhikh National Medical Research Center of ColoproctologyRussian FederationФГБУ "НМИЦ колопроктологии имени А.Н.Рыжих" Минздрава РоссииРоссияRyzhikh National Medical Research Center of ColoproctologyRussian FederationФГБУ "НМИЦ колопроктологии имени А.Н.Рыжих" Минздрава России; ГБУЗ «Московский клинический научно-практический центр имени А.С.Логинова Департамента здравоохранения Москвы»РоссияRyzhikh National Medical Research Center of Coloproctology; Moscow Clinical Scientific Center named after A.S. LoginovRussian Federation2021210920212034350Copyright © Подольская Д.В., Шапина М.В., Баранова Т.А., Тишаева И.А., Александров Т.Л., Князев О.В., Нанаева Б.А., 20212021Подольская Д.В., Шапина М.В., Баранова Т.А., Тишаева И.А., Александров Т.Л., Князев О.В., Нанаева Б.А.Podolskaya D.V., Shapina M.V., Baranova T.A., Tishaeva I.A., Alexandrov T.L., Knyazev O.V., Nanaeva B.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.ruproctology.com/jour/article/view/1653

ЦЕЛЬ: оценить эффективность применения тофацитиниба в качестве второй линии.ПАЦИЕНТЫ И МЕТОДЫ: в исследование включено 12 пациентов, из них 4 (33,34%) мужчин и 8 (66,66%) женщин. Возраст больных составил, в среднем, 41 ± 5 лет. Все пациенты (100%) госпитализированы с тяжелой атакой язвенного колита, которая являлась критерием включения пациентов в данное исследование. Клинические проявления, лабораторные показатели, состояние слизистой оболочки толстой кишки, по данным эндоскопического исследования, оценивались на момент назначения тофацитиниба на 3 и 7 сутки, а также через 12 недель.РЕЗУЛЬТАТЫ: быстрый клинический ответ на 3-й день лечения, характеризующийся урежением частоты стула, уменьшением примеси крови в стуле был отмечен у 10 (83,3%) из 12 пациентов. Через 7 дней от начала терапии ТФЦБ у всех пациентов (100%) отмечалось снижение активности тяжелой атаки до легкой, так же отмечалось снижение воспалительных маркеров анализов крови, нормализация уровня гемоглобина. В ходе наблюдения в течение 12 недель у 100% пациентов выявлена положительная клинико-лабораторная динамика. У 10 (83,4%) пациентов была отмечена ремиссия воспалительного процесса или сохранение минимальной активности.ЗАКЛЮЧЕНИE: полученные в нашем исследовании промежуточные результаты показывают, что применение ТФЦБ у гормонорезистентных пациентов может быть эффективным в качестве второй линии «терапии спасения».

AIM: to evaluate the effectiveness of tofacitinib as a second line treatment.PATIENTS AND METHODS: the study included 12 patients, 4 (33.34%) males and 8 (66.66%) females. The median age was 41 ± 5 years. All patients admitted to the hospital with a severe flare-up of ulcerative colitis, which was the inclusion criterion in this study. Clinical manifestations, laboratory parameters, and colonoscopy were done at the time of administration of tofacitinib, on days 3 and 7, and after 12 weeks.RESULTS: a fast clinical response on 3 day of treatment, reduction in stool frequency, decrease blood in stool was noted in 10 (83.3%) patients. After 7 days from the start of TFCS therapy, all patients showed a decrease from severe activity to mild activity, as well as a decrease in inflammatory blood markers and hemoglobin levels. During the follow-up for 12 weeks, 100% of patients showed positive clinical and laboratory changes. In 10 (83.4%) patients, remission or maintenance of negligible minimal activity was noted.CONCLUSION: the results obtained show that the use of TFTB in hormone-resistant patients can be effective as a second line of “rescue therapy”.

воспалительные заболевания кишечникатофацитинибязвенный колитinflammatory bowel diseasestofacitinibulcerative colitisReferencesИвашкин В.Т., Шелыгин Ю.А., Белоусова Е.А., Абдулганиева Д.И., и соавт. Проект клинических рекомендаций по диагностике и лечению язвенного колита. Колопроктология. 2019;18(4):7–36. DOI: 10.33878/2073-7556-2019-18-4-7-36Ivashkin V.T., Shelygin Yu.A., Belousova E.A., Abdulganieva D.I., et al. Project: clinical guidelines for the diagnostics and treatment of ulcerative colitis. Koloproktologia. 2019;18(4):7–36. https:// doi.org/10.33878/2073-7556-2019-18-4-7-36 (in Russ.).Князев О.В., Шкурко Т.В., Каграманова А.В., и соавт. Эпидемиология воспалительных заболеваний кишечника. Современное состояние проблемы (обзор литературы). Доказательная гастроэнтерология. 2020;9(2):72–79. DOI: 10.17116/dokgastro2020902172Knyazev O.V., Shkurko T.V., Fadeyeva N.A., et al. Epidemiology of chronic inflammatory bowel disease. Yesterday, today, tomorrow. Eksperimental’naya i Klinicheskaya Gastroenterologiya. 2017;139(3):4–12. (in Russ.).Dignass A, Lindsay JO, Sturm A. et al. Second European evidencebased consensus on the diagnosis and management of ulcerative colitis Part 2: Current management. Journal of Crohn’s and Colitis. Volume 6, Issue 10, 1 December 2012. DOI: 10.1016/j.crohns.2012.09.002Dignass A, Lindsay JO, Sturm A, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 2: Current management. Journal of Crohn’s and Colitis. Volume 6, Issue 10, 1 December 2012. DOI http:// dx.doi.org/10.1016/j.crohns.2012.09.002.Воробьев Г.И., Халиф И.Л. Неспецифические воспалительные заболевания кишечника. М.: Миклош, 2008. 400 c.Vorobev G.I., Khalif I.L. Non-specific inflammatory bowel disease. M.: Miklosh, 2008; 400 p. (in Russ.).Князев О.В., Чурикова А.А. Антицитокиновая терапия и качество жизни больных воспалительными заболеваниями кишечника. Доказательная гастроэнтерология. 2014;2:17–23.Knyazev O.V., Churikova A.A. Anti-cytokine therapy and the quality of life in the patients presenting with inflammatory intestinal disorders. Dokazatel’naya gastroenterologia. 2014;2:17–23. (in Russ.).Yanai H, Hanauer SB. Assessing response and loss of response to biological therapies in IBD. Am J Gastroenterol. 2011;106:685–98.Yanai H, Hanauer SB. Assessing response and loss of response to biological therapies in IBD. Am J Gastroenterol. 2011;106:685–98.Peyrin-Biroulet L. et al. Treatment satisfaction, preferences and perception gaps between patients and physicians in the ulcerative colitis CARES study: a real world-based study. Dig Liver Dis. 2016;48(6):601–7.Peyrin-Biroulet L, et al. Treatment satisfaction, preferences and perception gaps between patients and physicians in the ulcerative colitis CARES study: a real world-based study. Dig Liver Dis. 2016;48(6):601–7.D’Amico F, Parigi TL, Fiorino G. et al. Tofacitinib in the treatment of ulcerative colitis: efficacy and safety from clinical trials to real-world experience. Therap Adv Gastroenterol. 2019;12:1756284819848631.D’Amico F, Parigi TL, Fiorino G, et al. Tofacitinib in the treatment of ulcerative colitis: efficacy and safety from clinical trials to real-world experience. Therap Adv Gastroenterol. 2019;12:1756284819848631.Sandborn WJ, Su C, Sands BE. et al. OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain Investigators. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2017;376:1723–36.Sandborn WJ, Su C, Sands BE, et al. OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain Investigators. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2017;376:1723–36.Food and Drug Administration. FDA Approves New Treatment for Moderately to Severely Active Ulcerative Colitis. http://www.fda.gov/newsevents/ press-announcements/fda-approves-newtreatment-moderatelyseverely-active-ulcerative-colitis Accessed January 21, 2020. Czarska-thorley D. Xeljanz. European Medicines Agency. https://www.ema.europa.eu/en/medicines/human/referrals/xeljanz Accessed January, 21, 2020.Food and Drug Administration. FDA Approves New Treatment for Moderately to Severely Active Ulcerative Colitis. http://www.fda.gov/newsevents/press-announcements/fda-approves-newtreatment-moderatelyseverely-active-ulcerativecolitis Accessed January 21, 2020. Czarska-thorley D. Xeljanz. European Medicines Agency. https://www.ema.europa.eu/en/medicines/human/referrals/xeljanz Accessed January, 21, 2020.Hanauer S, Panaccione R, Danese S. et al. Tofacitinib induction therapy reduces symptoms within 3 days for patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2019;17:139–47.Hanauer S, Panaccione R, Danese S, et al. Tofacitinib induction therapy reduces symptoms within 3 days for patients with ulcerative colitis. Clin Gastroenterol Hepatol. 2019;17:139–47.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;11:769–84.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;11:769–84.Singh S, Allegretti JR, Siddique SM, Terdiman JP. AGA technical review on the management of moderate to severe ulcerative colitis. Gastroenterology. 2020, Jan 13. DOI: 10.1053/j.gastro.2020.01.007. [Epub ahead of print.]Singh S, Allegretti JR, Siddique SM, Terdiman JP. AGA technical review on the management of moderate to severe ulcerative colitis. Gastroenterology. 2020, Jan 13. doi: 10.1053/j.gastro.2020.01.007. [Epub ahead of print.]Narula N, Marshall JK, Colombel JF. 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;111:477–91.Narula N, Marshall JK, Colombel JF, 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;111:477–91.Narula N, Fine M, Colombel JF, Marshall JK, Reinisch W. Systematic review: sequential rescue therapy in severe ulcerative colitis: do the benefits outweigh the risks? Inflamm Bowel Dis. 2015;21:1683–94.Narula N, Fine M, Colombel JF, Marshall JK, Reinisch W. Systematic review: sequential rescue therapy in severe ulcerative colitis: do the benefits outweigh the risks? Inflamm Bowel Dis. 2015;21:1683–94.Berinstein JA, Steiner CA, Regal RE. et al. Efficacy of induction therapy with high-intensity tofacitinib in 4 patients with acute severe ulcerative colitis. Clin Gastroenterol Hepatol. 2019;17:988–90.e1.Berinstein JA, Steiner CA, Regal RE, et al. Efficacy of induction therapy with high-intensity tofacitinib in 4 patients with acute severe ulcerative colitis. Clin Gastroenterol Hepatol. 2019;17:988–90.e1.Kotwani P, Terdiman J, Lewin S. Tofacitinib for rescue therapy in acute severe ulcerative colitis: a real-world experience. J Crohns Colitis. 2020, Feb 5. DOI: 10.1093/ecco-jcc/jjaa018. [Epub ahead of print.]Kotwani P, Terdiman J, Lewin S. Tofacitinib for rescue therapy in acute severe ulcerative colitis: a real-world experience. J Crohns Colitis. 2020, Feb 5. DOI: 10.1093/ecco-jcc/jjaa018. [Epub ahead of print.]Paschos P, Katsoula A, Giouleme O. et al. Tofacitinib for induction of remission in ulcerative colitis: systematic review and metaanalysis. Ann Gastroenterol. 2018;31:572–82.Paschos P, Katsoula A, Giouleme O, et al. Tofacitinib for induction of remission in ulcerative colitis: systematic review and meta-analysis. Ann Gastroenterol. 2018;31:572–82.Lohan C, Diamantopoulos A, LeReun C. et al. Tofacitinib for the treatment of moderately to severely active ulcerative colitis: a systematic review, network meta-analysis and economic evaluation. BMJ Open Gastroenterol. 2019;6:e000302.Lohan C, Diamantopoulos A, LeReun C, el al. Tofacitinib for the treatment of moderately to severely active ulcerative colitis: a systematic review, network meta-analysis and economic evaluation. BMJ Open Gastroenterol. 2019;6:e000302.Singh S, Murad MH, Fumery M. et al. First- and second-line pharmacotherapies for patients with moderate to severely active ulcerative colitis: an updated network meta-analysis. Clin Gastroenterol Hepatol. 2020. DOI: 10.1016/j.cgh.2020.01.008Singh S, Murad MH, Fumery M, et al. First- and second line pharmacotherapies for patients with moderate to severely active ulcerative colitis: an updated network meta-analysis. Clin Gastroenterol Hepatol. 2020. doi: 10.1016/j.cgh.2020.01.008Singh S, Allegretti JR, Siddique SM, Terdiman JP. AGA technical review on the management of moderate to severe ulcerative colitis. Gastroenterology. 2020, Jan 13. DOI: 10.1053/j.gastro.2020.01.007Singh S, Allegretti JR, Siddique SM, Terdiman JP. AGA technical review on the management of moderate to severe ulcerative colitis. Gastroenterology. 2020, Jan 13. DOI: 10.1053/j.gastro.2020.01.007.Food and Drug Administration. Safety Trial Finds Risk of Blood Clots in the Lungs and Death With Higher Dose of Tofacitinib [Xeljanz, Xeljanz XR] in Rheumatoid Arthritis Patients; FDA to Investigate. https://www.fda.gov/drugs/ drug-safety-and-availability/safetytrial-finds-risk-blood-clots-lungs-anddeath-higher-dose-tofacitinibxeljanz-xeljanz-xr Accessed January 21, 2020.Food and Drug Administration. Safety Trial Finds Risk of Blood Clots in the Lungs and Death With Higher Dose of Tofacitinib [Xeljanz, Xeljanz XR] in Rheumatoid Arthritis Patients; FDA to Investigate. https://www.fda.gov/drugs/drug-safety-and-availability/safety-trial-finds-risk-blood-clots-lungsanddeath-higher-dose-tofacitinib-xeljanz-xeljanzxr Accessed January 21, 2020.Белоусова Е.А., Абдулганиева Д.И., Алексеева О.П., и соавт. Опыт применения тофацитиниба в терапии язвенного колита в условиях реальной клинической практики. Колопроктология. 2019;18(4):86–99.Belousova E.A., Abdulganieva В.I., Alekseeva O.P., et al. Experience of tofacitinib using in therapy of ulcerative colitis in real clinical practice. Koloproktologia. 2019;18(4):86–99. https://doi.org/10.33878/2073-7556-2019-18-4-86-99 (in Russ.).Taxonera С, Olivares D, Alba C. Real-World Effectiveness and Safety of Tofacitinib in Patients With Ulcerative Colitis: Systematic Review With Meta-Analysis. Inflamm Bowel Dis. 2021 Feb 15;izab011. DOI: 10.1093/ibd/izab011Taxonera С, Olivares D, Alba C. Real-World Effectiveness and Safety of Tofacitinib in Patients With Ulcerative Colitis: Systematic Review With Meta-Analysis. Inflamm Bowel Dis. 2021 Feb 15;izab011. DOI: 10.1093/ibd/izab011D’Amico F, Peyrin-Biroulet L, Danese S. Tofacitinib for Acute Severe Colitis: When the going Gets Tough, the Tough Get Going. Journal of Crohn’s and Colitis. 2020:1–3. DOI: 10.1093/ecco-jcc/jjaa028D’Amico F, Peyrin-Biroulet L, Danese S. Tofacitinib for Acute Severe Colitis: When the going Gets Tough, the Tough Get Going. Journal of Crohn’s and Colitis. 2020,1–3. DOI: 10.1093/ecco-jcc/jjaa028Peyrin-Biroulet L, Sandborn W, Sands BE. et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol.2015;110:1324–1338.Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015; 110:1324-1338.Hanauer S, Panaccione R, Danese S. et al. Tofacitinib achieves symptomatic improvement within 3 days in moderately to severely active ulcerative colitis, regardless of prior tumour necrosis factor inhibitor treatment status: results from OCTAVE induction 1 and 2. Journal of Crohn’s and Colitis. 2018;12:S046–S048. DOI: 10.1093/ecco-jcc/jjxl80.061Hanauer S, Panaccione R, Danese S et al. Tofacitinib achieves symptomatic improvement within 3 days in moderately to severely active ulcer-ative colitis, regardless of prior tumour necrosis factor inhibitor treatment status: results from OCTAVE induction 1 and 2. Journal of Crohn’s and Colitis.

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