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Theoretical aspects of prescribing ustekinumab as first-line therapy for Crohn’s disease

https://doi.org/10.21518/ms2023-138

Abstract

The treatment of Crohn’s disease is a complex process in which it is necessary to take into account not only the current condition of the patient and the risks of disease progression, but also the sequence of therapy. To date, only biological drugs can change the course of the disease, but their number is limited and they should be prescribed taking into account the choice of the optimal sequence for each patient, since the effectiveness of any biological drug is affected by previous treatment. Unfortunately, there are no common recommendations on the sequence of choosing biological drugs, and the issue of choosing a first-line drug is relevant. Ustekinumab is a biologic agent targeting interleukin-12 and 23 that has been shown to be effective and safe in the treatment of both patients after TNF-alpha inhibitors and bionaive patients. It has also been shown to be effective in the treatment of strictures and perianal manifestations of Crohn’s disease. Ustekinumab is also effective against articular extraintestinal manifestations such as arthralgia and psoriatic arthritis. A high response rate to ustekinumab was also found in patients with dermatological manifestations – psoriasis, pyoderma gangrenosum, and erythema nodosum. In addition, a good safety profile allows its use in elderly patients. Of particular interest is the direct comparison of biologics. To date, there is only one randomized head-to-head trial of ustekinumab and adalimumab showing comparable efficacy results. And there is also data from a post hoc analysis of randomized trials, where its effectiveness is comparable to infliximab. Thus, ustekinumab can be prescribed for the treatment of Crohn’s disease, including in the first line of therapy.

About the Author

M. V. Shapina
Ryzhikh State Scientific Center of Coloproctology
Russian Federation

Marina V. Shapina, Cand. Sci. (Med.), Head of the Department of Functional and Inflammatory Bowel Diseases 

2, Salyam Adil St., Moscow, 123423



References

1. Ivashkin V.T., Shelygin Yu.A., Abdulganieva D.I., Abdulkhakov R.A., Alekseeva O.P., Alekseenko S.A. and et al. Crohn’s disease. clinical recommendations (preliminary version). Koloproktologia. 2020;19(2):8–38. (In Russ.) https://doi.org/10.33878/2073-7556-2020-19-2-8-38.

2. Roda G., Chien Ng S., Kotze P.G., Argollo M., Panaccione R., Spinelli A. et al. Crohn’s disease. Nat Rev Dis Primers. 2020;6(1):22. https://doi.org/10.1038/s41572-020-0156-2.

3. Hanauer S.B., Feagan B.G., Lichtenstein G.R., Mayer L.F., Schreiber S., Colombel J.F. et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359(9317):1541–1549. https://doi.org/10.1016/S0140-6736(02)08512-4.

4. Hanauer S.B., Sandborn W.J., Rutgeerts P., Fedorak R.N., Lukas M., MacIntosh D. et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology. 2006;130(2):323–333. https://doi.org/10.1053/j.gastro.2005.11.030.

5. Colombel J.F., Sandborn W.J., Rutgeerts P., Enns R., Hanauer S.B., Panaccione R. et al. et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007;132(1):52–65. https://doi.org/10.1053/j.gastro.2006.11.041.

6. Colombel J.F., Sandborn W.J., Reinisch W., Mantzaris G.J., Kornbluth A., Rachmilewitz D. et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362(15):1383–1395. https://doi.org/10.1056/NEJMoa0904492.

7. Sandborn W.J., Feagan B.G., Rutgeerts P., Hanauer S., Colombel J.F., Sands B.E. et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013;369(8):711–721. https://doi.org/10.1056/NEJMoa1215739.

8. Sandborn W.J., Gasink C., Gao L.L., Blank M.A., Johanns J., Guzzo C. et al. Ustekinumab induction and maintenance therapy in refractory Crohn’s disease. N Engl J Med. 2012;367(16):1519–1528. https://doi.org/10.1056/NEJMoa1203572.

9. Papp K.A., Griffiths C.E., Gordon K., Lebwohl M., Szapary P.O., Wasfi Y. et al. Longterm safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up. Br J Dermatol. 2013;168(4):844–854. https://doi.org/10.1111/bjd.12214.

10. Hanauer S.B., Sandborn W.J., Feagan B.G., Gasink C., Jacobstein D., Zou B. et al. IM-UNITI: Three-year Efficacy, Safety, and Immunogenicity of Ustekinumab Treatment of Crohn’s Disease. J Crohns Colitis. 2020;14(1):23–32. https://doi.org/10.1093/ecco-jcc/jjz110.

11. Sands B.E., Sandborn W.J., Panaccione R., O’Brien C.D., Zhang H., Johanns J. et al. Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2019;381(13):1201–1214. https://doi.org/10.1056/NEJMoa1900750.

12. Rubenstein J.H., Chong R.Y., Cohen R.D. Infliximab decreases resource use among patients with Crohn’s disease. J Clin Gastroenterol. 2002;35(2):151–156. https://doi.org/10.1097/00004836-200208000-00007.

13. Schnitzler F., Fidder H., Ferrante M., Noman M., Arijs I., Van Assche G. et al. Longterm outcome of treatment with infliximab in 614 patients with Crohn’s disease: results from a single-centre cohort. Gut. 2009;58(4):492–500. https://doi.org/10.1136/gut.2008.155812.

14. Qiu Y., Chen B.L., Mao R., Zhang S.H., He Y., Zeng Z.R. et al. Systematic review with meta-analysis: loss of response and requirement of anti-TNFα dose intensification in Crohn’s disease. J Gastroenterol. 2017;52(5):535–554. https://doi.org/10.1007/s00535-017-1324-3.

15. Feagan B.G., Sandborn W.J., Gasink C., Jacobstein D., Lang Y., Friedman J.R. et al. Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease. N Engl J Med. 2016;375(20):1946–1960. https://doi.org/10.1056/NEJMoa1602773.

16. Johnson A.M., Barsky M., Ahmed W., Zullow S., Galati J., Jairath V. et al. The RealWorld Effectiveness and Safety of Ustekinumab in the Treatment of Crohn’s Disease: Results From the SUCCESS Consortium. Am J Gastroenterol. 2023;118(2):317–328. https://doi.org/10.14309/ajg.0000000000002047.

17. Garg R., Aggarwal M., Butler R., Achkar J.P., Lashner B., Philpott J. et al. RealWorld Effectiveness and Safety of Ustekinumab in Elderly Crohn’s Disease Patients. Dig Dis Sci. 2022;67(7):3138–3147. https://doi.org/10.1007/s10620-021-07117-9.

18. Asscher V.E.R., Biemans V.B.C., Pierik M.J., Dijkstra G., Löwenberg M., van der Marel S. et al. Comorbidity, not patient age, is associated with impaired safety outcomes in vedolizumab- and ustekinumab-treated patients with inflammatory bowel disease-a prospective multicentre cohort study. Aliment Pharmacol Ther. 2020;52(8):1366–1376. https://doi.org/10.1111/apt.16073.

19. Sands B.E., Gasink C., Jacobstein D., Gao L.L., Johanns J., Colombel J.F. et al. Fistula healing in pivotal studies of ustekinumab in Crohn’s disease. Gastroenterology. 2017;152(5):S185. https://doi.org/10.1016/S0016-5085(17)30930-7.

20. Singh S., Proctor D., Scott F.I., Falck-Ytter Y., Feuerstein J.D. AGA Technical Review on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Crohn’s Disease. Gastroenterology. 2021;160(7):2512–2556.e9. https://doi.org/10.1053/j.gastro.2021.04.023.

21. Sandborn W.J., Rebuck R., Wang Y., Zou B., Adedokun O.J., Gasink C. et al. Five-Year Efficacy and Safety of Ustekinumab Treatment in Crohn’s Disease: The IM-UNITI Trial. Clin Gastroenterol Hepatol. 2022;20(3):578–590.e4. https://doi.org/10.1016/j.cgh.2021.02.025.

22. Peyrin-Biroulet L., Panaccione R., Gasink C., Hoops T., Izanec J.L., Ma T. et al. P495 Perianal fistula closure in patients receiving ustekinumab: Results from the SEAVUE and STARDUST trials. In: Egan L.J. (ed.). Abstracts of the 17th Congress of ECCO Virtual, February 16–19, 2022. Vienna; 2022, p. i460. Available at: https://www.ecco-ibd.eu/publications/congress-abstracts/item/p495-perianalfistula-closure-in-patients-receiving-ustekinumab-results-from-the-seavueand-stardust-trials.html.

23. Chapuis-Biron C., Kirchgesner J., Pariente B., Bouhnik Y., Amiot A., Viennot S. et al. Ustekinumab for Perianal Crohn’s Disease: The BioLAP Multicenter Study From the GETAID. Am J Gastroenterol. 2020;115(11):1812–1820. https://doi.org/10.14309/ajg.0000000000000810.

24. Attauabi M., Burisch J., Seidelin J.B. Efficacy of ustekinumab for active perianal fistulizing Crohn’s disease: a systematic review and meta-analysis of the current literature. Scand J Gastroenterol. 2021;56(1):53–58. https://doi.org/10.1080/00365521.2020.1854848.

25. Narula N., Wong E.C.L., Dulai P.S., Marshall J.K., Colombel J.F., Reinisch W. Outcomes of Passable and Non-passable Strictures in Clinical Trials of Crohn’s Disease: A Post-hoc Analysis. J Crohns Colitis. 2021;15(10):1649–1657. https://doi.org/10.1093/ecco-jcc/jjab045.

26. El Ouali S., Ottichilo R.K., Atkinson N., Lu C., Bruining D.H., Qazi T. et al. Su487 Vedolizumab and ustekinumab for the treatment of symptomatic small bowel stricturing Crohn’s disease – results from an observational cohort study. Gastroenterology. 2021;160(6):S-713. https://doi.org/10.1016/S0016-5085(21)02409-4.

27. Narula N., Aruljothy A., Wong E.C.L., Homenauth R., Alshahrani A.A., Marshall J.K., Reinisch W. The impact of ustekinumab on extraintestinal manifestations of Crohn’s disease: A post hoc analysis of the UNITI studies. United European Gastroenterol J. 2021;9(5):581–589. https://doi.org/10.1002/ueg2.12094.

28. Guillo L., D’Amico F., Danese S., Peyrin-Biroulet L. Ustekinumab for Extraintestinal Manifestations of Inflammatory Bowel Disease: A Systematic Literature Review. J Crohns Colitis. 2021;15(7):1236–1243. https://doi.org/10.1093/ecco-jcc/jjaa260.

29. Tursi A., Mocci G., Maconi G. Effect of Ustekinumab on Extraintestinal Diseases in Refractory Crohn’s Disease. J Crohns Colitis. 2021;15(8):1399–1400. https://doi.org/10.1093/ecco-jcc/jjab028.

30. Irving P.M., Sands B.E., Hoops T., Izanec J.L., Gao L.L., Gasink C. et al. OP02 Ustekinumab versus adalimumab for induction and maintenance therapy in Moderate-to-Severe Crohn’s Disease: The SEAVUE study. In: Abstracts of the 16th Congress of ECCO Virtual, July 2–3 & 8–10, 2021. Vienna; 2021, pp. S001–S002. Available at: https://www.ecco-ibd.eu/publications/congress-abstracts/item/op02-ustekinumab-versus-adalimumab-for-induction-and-maintenancetherapy-in-moderate-to-severe-crohn-s-disease-the-seavue-study.html.

31. Narula N., Wong E.C.L., Dulai P.S., Sengupta N.K., Marshall J.K., Colombel J.F., Reinisch W. Comparative Efficacy and Rapidity of Action for Infliximab vs Ustekinumab in Biologic Naïve Crohn’s Disease. Clin Gastroenterol Hepatol. 2022;20(7):1579–1587.e2. https://doi.org/10.1016/j.cgh.2021.04.006.

32. Biemans V.B.C., van der Woude C.J., Dijkstra G., van der Meulen-de Jong A.E., Löwenberg M., de Boer N.K. et al. Ustekinumab is associated with superior effectiveness outcomes compared to vedolizumab in Crohn’s disease patients with prior failure to anti-TNF treatment. Aliment Pharmacol Ther. 2020;52(1):123–134. https://doi.org/10.1111/apt.15745.

33. Ko Y., Paramsothy S., Yau Y., Leong R.W. Superior treatment persistence with ustekinumab in Crohn’s disease and vedolizumab in ulcerative colitis compared with anti-TNF biological agents: real-world registry data from the Persistence Australian National IBD Cohort (PANIC) study. Aliment Pharmacol Ther. 2021;54(3):292–301. https://doi.org/10.1111/apt.16436.

34. Scott F.I., Hans A.K., Gerich M.E., Fennimore B., Mamtani R., Vajravelu R.K., Lewis J.D. Identification of the Most Effective Position for Ustekinumab in Treatment Algorithms for Crohn`s Disease. Clin Gastroenterol Hepatol. 2021;19(10):2082–2092.e10. https://doi.org/10.1016/j.cgh.2020.08.021.

35. Torres J., Bonovas S., Doherty G., Kucharzik T., Gisbert J.P., Raine T. et al. ECCO Guidelines on Therapeutics in Crohn’s Disease: Medical Treatment. J Crohns Colitis. 2020;14(1):4–22. https://doi.org/10.1093/ecco-jcc/jjz180.

36. D’Amico F., Fiorino G., Furfaro F., Allocca M., Roda G., Loy L. et al. Patient’s profiling for therapeutic management of inflammatory bowel disease: a tailored approach. Expert Rev Gastroenterol Hepatol. 2020;14(9):765–773. https://doi.org/10.1080/17474124.2020.1772057.

37. Singh S., Murad M.H., Fumery M., Sedano R., Jairath V., Panaccione R. et al. Comparative efficacy and safety of biologic therapies for moderate-to-severe Crohn’s disease: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol. 2021;6(12):1002–1014. https://doi.org/10.1016/S2468-1253(21)00312-5.

38. Chateau T., Bonovas S., Le Berre C., Mathieu N., Danese S., Peyrin-Biroulet L. Vedolizumab Treatment in Extra-Intestinal Manifestations in Inflammatory Bowel Disease: A Systematic Review. J Crohns Colitis. 2019;13(12):1569–1577. https://doi.org/10.1093/ecco-jcc/jjz095.

39. Panés J., Rimola J. Perianal fistulizing Crohn’s disease: pathogenesis, diagnosis and therapy. Nat Rev Gastroenterol Hepatol. 2017;14(11):652–664. https://doi.org/10.1038/nrgastro.2017.104.


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For citations:


Shapina MV. Theoretical aspects of prescribing ustekinumab as first-line therapy for Crohn’s disease. Meditsinskiy sovet = Medical Council. 2023;(8):175-180. (In Russ.) https://doi.org/10.21518/ms2023-138

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