Preview

Russian Journal of Gastroenterology, Hepatology, Coloproctology

Advanced search

New Possibilities for the Treatment of Crohn’s Disease

https://doi.org/10.22416/1382-4376-2019-29-5-13-20

Abstract

Aim. To review data on the efficiency and safety of using Ustekinumab in patients with Crohn’s disease.

Key findings. Ustekinumab is a fully human monoclonal antibody of the IgG1k class to the p40 subunit of IL-12 and IL-23. The drug interrupts the cascade of humoral and cellular reactions leading to transmural inflammation of the intestinal wall by blocking the interaction of the p40 subunit with the IL-12Rβ1 chain on the surface of T-lymphocytes and NK cells. A number of placebo-controlled studies have demonstrated the effectiveness of Ustekinumab in the induction and the maintenance of remission in those patients with Crohn’s disease who showed no response to conventional therapy (glucocorticosteroids and immunosuppressants) and therapy with TNF-α antagonists. In addition, the efficiency of Ustekinumab in maintaining a clinical response and clinical remission over two years of therapy has been shown. The drug has a favourable safety profile and a low immunogenicity.

Conclusion. The reviewed studies show Ustekinumab to be an effective and safe drug for the induction and the maintenance of clinical remission in patients with Crohn’s disease.

About the Authors

Z. A. Mamieva
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Zarina A. Mamieva — Postgraduate Student, Propaedeutics of Internal Diseases Department

19991, Moscow, Pogodinskaya str., 1, building 1.



E. A. Poluektova
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Elena A. Poluektova* — Dr. Sci. (Med.), Prof., Propaedeutics of Internal Diseases Department

19991, Moscow, Pogodinskaya str., 1, building 1.



O. S. Shifrin
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Oleg S. Shifrin — Dr. Sci. (Med.), Prof., Propaedeutics of Internal Diseases Department

19991, Moscow, Pogodinskaya str., 1, building 1.



References

1. Ивашкин В.Т., Шелыгин Ю.А., Халиф И.Л. и др.Клинические рекомендации Российской гастроэнтерологической ассоциации и Ассоциации колопроктологов России по диагностике и лечению болезни Крона. Колопроктология 2017;2(60):7–29. [Ivashkin V.T., Shelygin Yu.A., Khalif I.L. et al. Clinical recommendations of the Russian Gastroenterological Association and the Association of Coloproctologists of Russia on the diagnosis and treatment of Crohn’s disease. Coloproctology 2017;2(60): 7–29 (In Rus.)].

2. Faubion W.A., Loftus E.V., Harmsen W.S., Zinsmeister A.R., Sandborn W.J. The natural history of corticosteroid therapy for inflammatory bowel disease: a populationbased study. Gastroenterology. 2001;121:255–60.

3. Peyrin-Biroulet L., Khosrotehrani K., Carrat F. et al. Increased risk for non-melanoma skin cancers in patients who receive thiopurines for inflammatory bowel disease. Gastroenterology. 2011;141:1621–8.e1.

4. Beaugerie L., Brousse N, Bouvier A.M. et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet. 2009;374:1617–25.

5. Bourrier A., Carrat F., Colombel J.F. et al. Excess risk of urinary tract cancers in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Aliment. Pharmacol. Ther. 2016;43:252–61.

6. Qiu Y., Chen B.L., Mao R. et al. Systematic review with meta-analysis: loss of response and requirement of antiTNFalpha dose intensification in Crohn’s disease. J. Gastroenterol. 2017;52(5):535–54.

7. STELARA® (ustekinumab) Product Monograph. Janssen (http://www.janssenlabels.com/package-insert/productmonograph/prescribing-information/STELARA-pi.pdf).

8. Torres J., Mehandru S., Colombel., J.-F., Peyrin-Biroulet L. Crohn’s disease. Lancet. 2017;389(10080):1741–55.

9. Verstockt B., Van Assche G., Vermeire S., Ferrante M. Biological therapytargeting the IL-23/IL-17 axis in inflammatory bowel disease. Expert Opin. Biol. Ther. 2017;17(1):31–47.

10. Blanco P., Palucka A.K., Pascual V., Banchereau J. Dendritic cells and cytokines in human inflammatory and autoimmune diseases. Cytokine Growth Factor Rev. 2008;19(1):41–52.

11. Oppmann B., Lesley R., Blom B. et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar aswell as distinct from IL-12. Immunity. 2000;13(5):715–25.

12. Presky D.H., Yang H., Minetti L.J. et al. A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. Proc Natl. Acad. Sci. USA. 1996;93(24):14002–7.

13. Sarra M., Pallone F., Macdonald T.T., Monteleone G. IL-23/IL-17 axis in IBD. Inflamm. Bowel Dis. 2010;16(10):1808–13.

14. Izcue A., Hue S., Buonocore S. et al. Interleukin-23 restrains regulatory T cell activity to drive T cell-dependent colitis. Immunity. 2008;28(4):559–70.

15. Parham C., Chirica M., Timans J. et al. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J. Immunol. 2002;168(11):5699–708.

16. Feagan B.G., Sandborn W.J., Gasink C. et al. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N. Engl. J. Med. 2016;375:1946–60.

17. Sandborn W., Gasink C., Chan D. et al. PD-012 endoscopic healing in the ustekinumab phase 3 UNITI/IMUNITI Crohn’s disease program and relationship of clinical outcomes to baseline ulceration status. Inflamm. Bowel Dis. 2017;23:S9.

18. Sandborn W.J., Rutgeerts P., Gasink C. et al. Longterm efficacy and safety of ustekinumab for Crohn’s disease through the second year of therapy. Aliment. Pharmacol. Ther. 2018;48:65–77.

19. Ma C., Fedorak R.N., Kaplan G.G. et al. Clinical, endoscopic and radiographic outcomes with ustekinumab in medically-refractory Crohn’s disease: real world experience from a multicentre cohort. Aliment. Pharmacol. Ther 2017;45:1232–43.

20. Harris K.A., Horst S., Gadani A. et al. Patients with refractory Crohn’s disease successfully treated with ustekinumab. Inflamm. Bowel Dis. 2016;22:397–401.

21. Ghosh S., Gensler L.S., Yang Z. et al. Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn’s Disease: An Integrated Analysis of Phase II/III Clinical Development Programs. Drug. Saf. 2019;42:751–68.

22. Danese S., Bonovas S., Peyrin-Biroulet L. Positioning ustekinumab in Crohn’s disease: from clinical evidence to clinical practice. J Crohns Colitis. 2017, 11(10): 1258-1266. doi: 10.1093/ecco-jcc/jjx079.

23. Armuzzi A., Ardizzone S., Biancone L., Castiglione F., Danese S., Gionchetti P., Orlando A., Rizzello F., Scribano M.L., Vecchi M., Daperno M. Ustekinumab in the management of Crohn's disease: Expert opinion. Dig Liver Dis. 2018;50(7):653-660. doi: 10.1016/j.dld.2018.02.017.


Review

For citations:


Mamieva Z.A., Poluektova E.A., Shifrin O.S. New Possibilities for the Treatment of Crohn’s Disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2019;29(5):13-20. (In Russ.) https://doi.org/10.22416/1382-4376-2019-29-5-13-20

Views: 2726


ISSN 1382-4376 (Print)
ISSN 2658-6673 (Online)