Comparative inflammatory bowel diseases therapy maintainence by biologics in real clinical practice: the retrospective cohort study results

Introduction. Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn's disease (CD) remain one of the urgent problems of modern gastroenterology, as they affect people of working age, have a recurrent progressive course, can be accompanied by disabling life-threatening complications and require in many cases constant expensive anti-relapse treatment. Biologics and JAK-inhibitors are the most effective in inducing and maintaining IBD remission, and the most pressing issue of their application is to assess whether this therapy will remain effective in the long term in real clinical practice.

The aim of the study: to assess the maintenance («survival») of therapy of CD and UC by biologics and JAK-inhibitors in real clinical practice.

Materials and methods. By the maintenance («survival») of therapy we mean the time period during which therapy was continued with a biologics and JAK-inhibitors until the moment of withdrawal due to ineffectiveness or intolerance, or until the last contact with the patient, if this therapy was not stopped. A retrospective cohort study was conducted on the basis of the specialized IBD city clinic, in which the medical documentation of 96 patients with IBD who received biologics and JAK-inhibitors in the framework of 144 episodes of therapy with the following drugs: infliximab, adalimumab, vedolizumab, ustekinumab, upadacitinib.

Results. The median duration of retrospective follow-up of CD patients was 173 weeks, UC patients – 93 weeks. At the end of the follow-up period, ustekinumab therapy continued in 87 % of patients, upadacitinib in 80 %, adalimumab in 52 %, vedolizumab in 40 %, infliximab in 11 %. According to the results of the Kaplan-Meier method, it was found that in CD, ustekinumab and upadacitinib had the greatest therapy maintenance, and the latter was superior to TNF-α inhibitors and vedolizumab only after 12 months of treatment. In UC patients ustekinumab had the greatest therapy maintenance: in none of the patients, therapy with this drug was discontinued due to ineffectiveness or intolerance. Multivariate analysis using the Cox regression, adjusted for bionaive patients, prescribing of the drug in the early period of the course of IBD and the age of diagnosis, allowed to establish that the risk of discontinuation of ustekinumab therapy due to ineffectiveness/intolerance in comparison with TNF-α inhibitors was lower by 4.8 times (95 % CI 1.9–12.5).

Conclusion. Considered in the study, biologics and JAK-inhibitors had different therapy maintenance, the best results on this parameter in real clinical practice was demonstrated by the interleukin‑12/23 inhibitor ustekinumab. However, when prescribing any existing biologics and JAKinhibitors, it is necessary to take into account the potential situation of loss of effect, which requires changing the drug used to another. For this reason, the search for new targeted drugs is relevant, among which the most promising is guselkumab, selectively inhibiting interleukin‑23, which demonstrated an advantage over ustekinumab in the framework of direct comparison in phase III clinical trials of both in relation to the onset of endoscopic response and endoscopic remission, and in the frequency of histological remission of CD by the 48th week of therapy.

1. Shelygin Yu.A. et al. Clinical recommendations. Crohn's disease (K50), adults. Coloproctology. 2023; 22 (3): 10–49 (in Russ.). https://doi.org/10.33878/2073-7556-2023-22-3-10-49

2. Shelygin Yu.A. et al. Clinical recommendations. Ulcerative colitis (K51), adults. Coloproctology. 2023; 22 (1): 10–44. (In Russ.). https://doi.org/10.33878/2073-7556-2023-22-1-10-44

3. Maaser C. et al. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019; 13 (2): 144–164. https://doi.org/10.1093/ecco-jcc/jjy113

4. Sturm A. et al. ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 2: IBD scores and general principles and technical aspects. J Crohns Colitis. 2019; 13 (3): 273–284. https://doi.org/10.1093/ecco-jcc/jjy114

5. Veselov A. V. et al. Assessment of the economic burden and the current state of organization of drug supply for patients with immunoinflammatory diseases (on the example of ulcerative colitis and Crohn's disease) in the Russian Federation. Problems of Social Hygiene, Health and History of Medicine. 2020; 28 (S 2): 1137–1145. (In Russ.). https://doi.org/10.32687/0869-866X-2020-28-s2-1137-1145

6. Belousova E. A. et al. Clinical and demographic characteristics and therapeutic approaches in patients with inflammatory bowel diseases (Crohn's disease, ulcerative colitis) in the Russian Federation. First results of the analysis of the National Register. Coloproctology. 2023; 22 (1): 65–82. (In Russ.). https://doi.org/10.33878/2073-7556-2023-22-1-65-82

7. Uspenskiy Y. P. et al. Features of a complicated course and extraintestinal manifestations of inflammatory bowel diseases. University Therapeutic Journal. 2023; 5 (2): 68–83. (In Russ.). https://doi.org/10.56871/UTJ.2023.72.18.006

8. Petrov S. V. et al. A clinical case of complicated Crohn's disease: difficulties in diagnosis and treatment. University Therapeutic Journal. 2022; 4 (3): 39–46. (In Russ.). https://doi.org/10.56871/1531.2022.49.85.005

9. Gordon H. et al. ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment. J Crohns Colitis. 2024; 18 (10): 1531–1555. https://doi.org/10.1093/ecco-jcc/jjae091

10. Raine T. et al. ECCO Guidelines on therapeutics in ulcerative colitis: medical treatment. J Crohns Colitis. 2022; 16 (1): 2–17. https://doi.org/10.1093/ecco-jcc/jjab178

11. Turner D. 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; 160 (5): 1570–1583. https://doi.org/10.1053/j.gastro.2020.12.031

12. Levitskaya A. V., Belousova E. A., Lomakina E. Yu., Teberdieva M. V. Comparative efficacy and survival of biologics in inflammatory bowel disease in different lines of therapy: the clinician’s view of the problem. Koloproktologia. 2025; 24 (1): 103–114. (In Russ.). https://doi.org/10.33878/2073-7556-2025-24-1-103-114

13. Khan S., Rupniewska E., Neighbors M. et al. Real-world evidence on adherence, persistence, switching and dose escalation with biologics in adult inflammatory bowel disease in the United States: A systematic review. J Clin Pharm Ther. 2019; 44 (4): 495–507. https://doi.org/10.1111/jcpt.12830

14. Chen C., Hartzema A. G., Xiao H. et al. Real-world pattern of biologic use in patients with inflammatory bowel disease: treatment persistence, switching, and importance of concurrent immunosuppressive therapy. Inflamm Bowel Dis. 2019; 25 (8): 1417–1427. https://doi.org/10.1093/ibd/izz001

15. D'Amico F., Bencardino S., Magro F. et al. Positioning Guselkumab in The Treatment Algorithm of Patients with Crohn's Disease. Biologics. 2025; 19: 351–363. Published 2025 May 31. DOI: 10.2147/BTT.S 530354

16. Atreya R., Allegretti J. R., Abreu M. T. et al. Guselkumab binding to CD 64+ IL-23-producing myeloid cells enhances potency for neutralizing IL-23 signaling. Oral Presentation presented at: United European Gastroenterology (UEG) Week; October 12–15, 2024; Vienna, Austria.

17. Richards D., Venkat S., Ruane D. et al. Guselkumab decreases key cellular inflammatory processes across ileum and colon tissue in Crohn’s Disease. Abstract presented at: United European Gastroenterology (UEG) Week; October 12–15, 2024; Vienna, Austria.

18. Fanizza J., D’Amico F., Lusetti F. et al. The role of IL-23 inhibitors in Crohn’s disease. J Clin Med. 2023; 13 (1): 224. https://doi.org/10.3390/jcm13010224

19. Peyrin-Biroulet L., Chapman J. C., Colombel J. F. et al. Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn’s Disease. N Engl J Med. 2024; 391 (3): 213–223. https://doi.org/10.1056/NEJMoa2314585

20. Zhou L., Wang Y., Wan Q. et al. A non-clinical comparative study of IL-23 antibodies in psoriasis. MAbs. 2021; 13 (1): 1964420. https://doi.org/10.1080/19420862.2021.1964420

21. Lee J. S., Tato C. M., Joyce-Shaikh B. et al. Interleukin-23-independent IL-17 production regulates intestinal epithelial permeability. Immunity. 2015; 43 (4): 727–738. https://doi.org/10.1016/j.immuni.2015.09.003

22. Levin A. A., Gottlieb A. B. Specific targeting of interleukin-23p19 as effective treatment for psoriasis. J Am Acad Dermatol. 2014; 70 (3): 555–561. https://doi.org/10.1016/j.jaad.2013.10.043

23. Deepak P., Sandborn W. J. Ustekinumab and anti-interleukin-23 agents in Crohn’s disease. Gastroenterol Clin North Am. 2017; 46 (3): 603–626. https://doi.org/10.1016/j.gtc.201

24. Panaccione R. et al. Efficacy and safety of guselkumab therapy in patients with moderately to severely active crohn’s disease: results of the GALAXI 2 & 3 Phase 3 Studies [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/efficacy-and-safety-of-guselkumab-therapy-in-patients-with-moderately-to-severely-active-crohns-disease-results-of-the-galaxi-2–3-phase-3-studies/. Accessed August 18, 2025.

25. Peyrin-Biroulet L., Allegretti J. R., Rubin D. T. et al. Guselkumab in patients with moderately to severely active ulcerative colitis: QUASAR phase 2b induction study. Gastroenterology. 2023; 165 (6): 1443–1457. https://doi.org/10.1053/j.gastro.2023.08.038

26. Rubin D. T., Allegretti J. R., Panes J. et al. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies. Lancet. 2025; 405 (10472): 33–49. https://doi.org/10.1016/S0140-6736 (24) 01927-5