Research progress on predictive factors for ustekinumab therapy in Crohn’s disease_West China Medical Journal

Authors：

SHE Yufen , ZHAO Ruiqi , ZHUANG Zhuoqing ,  ZHANG Yan

Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

ZHANG Yan, Email: hxzyan@163.com

Keywords：

Crohn’s disease; ustekinumab; predictive factors

DOI：

10.7507/1002-0179.202503133

Video：

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Ustekinumab (UST) is a humanized monoclonal antibody targeting the interleukin-12/23 pathway, which has been widely used in the therapy of Crohn’s disease. However, there are individual differences in patient response to UST. To identify the relevant factors affecting UST efficacy and provide evidence for individualized medication, this article systematically reviews and summarizes the research progress on predictive factors for UST therapy in Crohn’s disease in recent years. The content covers clinical characteristics, biomarkers, genetic factors, imaging indicators, endoscopic manifestations, drug metabolism and immune response, as well as comprehensive scoring models. It also summarizes and analyzes the predictive factors for UST dose optimization and the factors related to efficacy after optimization.

Citation： SHE Yufen, ZHAO Ruiqi, ZHUANG Zhuoqing, ZHANG Yan. Research progress on predictive factors for ustekinumab therapy in Crohn’s disease. West China Medical Journal, 2026, 41(3): 503-509. doi: 10.7507/1002-0179.202503133 Copy

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7.	Johnson AM, Barsky M, Ahmed W, et al. The real-world 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.
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9.	Hirayama H, Morita Y, Imai T, et al. Ustekinumab trough levels predicting laboratory and endoscopic remission in patients with Crohn’s disease. BMC Gastroenterol, 2022, 22(1): 195.
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1. Singh S, George J, Boland BS, et al. Primary non-response to tumor necrosis factor antagonists is associated with inferior response to second-line biologics in patients with inflammatory bowel diseases: a systematic review and meta-analysis. J Crohns Colitis, 2018, 12(6): 635-643.
2. Casanova MJ, Chaparro M, Mínguez M, et al. Effectiveness and safety of the sequential use of a second and third anti-tnf agent in patients with inflammatory bowel disease: results from the eneida registry. Inflamm Bowel Dis, 2020, 26(4): 606-616.
3. Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med, 2016, 375(20): 1946-1960.
4. Koo HM, Jun YK, Choi Y, et al. 10 years of biologic use patterns in patients with inflammatory bowel disease: treatment persistence, switching and dose intensification - a nationwide population-based study. Therap Adv Gastroenterol, 2023, 16: 17562848231201728.
5. Chetwood JD, Ko Y, Pudipeddi A, et al. Biological agents in the treatment of Crohn’s disease: a propensity score-matched analysis from the prospective persistence Australian national IBD cohort (PANIC3) study. Am J Gastroenterol, 2024, 119(8): 1536-1544.
6. 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.
7. Johnson AM, Barsky M, Ahmed W, et al. The real-world 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.
8. Hoffmann P, Krisam J, Wehling C, et al. Ustekinumab: “real-world” outcomes and potential predictors of nonresponse in treatment-refractory Crohn’s disease. World J Gastroenterol, 2019, 25(31): 4481-4492.
9. Hirayama H, Morita Y, Imai T, et al. Ustekinumab trough levels predicting laboratory and endoscopic remission in patients with Crohn’s disease. BMC Gastroenterol, 2022, 22(1): 195.
10. Lorenzo González L, Valdés Delgado T, Vázquez Morón JM, et al. Ustekinumab in Crohn’s disease: real-world outcomes and predictors of response. Rev Esp Enferm Dig, 2022, 114(5): 272-279.
11. Gisbert JP, Chaparro M. Primary failure to an anti-TNF agent in inflammatory bowel disease: switch (to a second anti-TNF agent) or swap (for another mechanism of action)?. J Clin Med, 2021, 10(22): 5318.
12. Hashash JG, Mourad FH. Positioning biologics in the management of moderate to severe Crohn’s disease. Curr Opin Gastroenterol, 2021, 37(4): 351-356.
13. Iborra M, Beltrán B, Fernández-Clotet A, et al. Real-world long-term effectiveness of ustekinumab in Crohn’s disease: results from the ENEIDA registry. Aliment Pharmacol Ther, 2020, 52(6): 1017-1030.
14. Khorrami S, Ginard D, Marín-Jiménez I, et al. Ustekinumab for the treatment of refractory Crohn’s disease: the Spanish experience in a large multicentre open-label cohort. Inflamm Bowel Dis, 2016, 22(7): 1662-1669.
15. Kubesch A, Rueter L, Farrag K, et al. Short and long-term effectiveness of ustekinumab in patients with Crohn’s disease: real-world data from a german IBD cohort. J Clin Med, 2019, 8(12): 2140.
16. Okuda H, Hosomi S, Itani S, et al. Pretreatment serum monocyte chemoattractant protein-1 as a predictor of long-term outcome by ustekinumab in patients with Crohn’s disease. J Gastroenterol Hepatol, 2023, 38(6): 910-920.
17. Biemans VBC, van der Meulen-de Jong AE, van der Woude CJ, et al. Ustekinumab for Crohn’s disease: results of the ICC registry, a nationwide prospective observational cohort study. J Crohns Colitis, 2020, 14(1): 33-45.
18. Esaki M, Ihara Y, Tominaga N, et al. Predictive factors of the clinical efficacy of ustekinumab in patients with refractory Crohn’s disease: tertiary centers experience in Japan. Int J Colorectal Dis, 2023, 38(1): 57.
19. Wils P, Bouhnik Y, Michetti P, et al. Subcutaneous ustekinumab provides clinical benefit for two-thirds of patients with Crohn’s disease refractory to anti-tumor necrosis factor agents. Clin Gastroenterol Hepatol, 2016, 14(2): 242-250. e1-e2.
20. Ma C, Fedorak RN, Kaplan GG, 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(9): 1232-1243.
21. Gutiérrez A, Rodríguez-Lago I. How to optimize treatment with ustekinumab in inflammatory bowel disease: lessons learned from clinical trials and real-world data. Front Med (Lausanne), 2021, 8: 640813.
22. Dalal RS, Njie C, Marcus J, et al. Predictors of ustekinumab failure in Crohn’s disease after dose intensification. Inflamm Bowel Dis, 2021, 27(8): 1294-1301.
23. Ollech JE, Normatov I, Peleg N, et al. Effectiveness of ustekinumab dose escalation in patients with Crohn’s disease. Clin Gastroenterol Hepatol, 2021, 19(1): 104-110.
24. Murate K, Maeda K, Nakamura M, et al. Endoscopic activity and serum TNF-α level at baseline are associated with clinical response to ustekinumab in Crohn’s disease patients. Inflamm Bowel Dis, 2020, 26(11): 1669-1681.
25. Onali S, Pugliese D, Caprioli FA, et al. An objective comparison of vedolizumab and ustekinumab effectiveness in Crohn’s disease patients’ failure to TNF-alpha inhibitors. Am J Gastroenterol, 2022, 117(8): 1279-1287.
26. Sandborn WJ, Feagan BG, Fedorak RN, et al. A randomized trial of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn’s disease. Gastroenterology, 2008, 135(4): 1130-1141.
27. Iborra M, Beltrán B, Nos P. Editorial: real-world short-term effectiveness of ustekinumab in 305 patients with Crohn’s disease-results from the ENEIDA registry. Authors’ reply. Aliment Pharmacol Ther, 2019, 50(5): 600-601.
28. Yao J, Zhang H, Su T, et al. Ustekinumab promotes radiological fistula healing in perianal fistulizing Crohn’s disease: a retrospective real-world analysis. J Clin Med, 2023, 12(3): 939.
29. Park J, Chun J, Yoon H, et al. Feasibility of a clinical decision support tool for ustekinumab to predict clinical remission and relapse in patients with Crohn’s disease: a multicenter observational study. Inflamm Bowel Dis, 2023, 29(4): 548-554.
30. Nigam GB, Limdi JK. An update on the role of anti-IL-12/IL23 agents in the management of inflammatory bowel disease. Br Med Bull, 2021, 138(1): 29-40.
31. Derikx LAAP, Plevris N, Su S, et al. Rates, predictive factors and effectiveness of ustekinumab intensification to 4- or 6-weekly intervals in Crohn’s disease. Dig Liver Dis, 2023, 55(8): 1034-1041.
32. Saleh A, Stading R, Miroballi N, et al. Therapeutic drug monitoring in patients with inflammatory bowel disease on ustekinumab. J Dig Dis, 2024, 25(4): 214-221.
33. Monin L, Dubois S, Reenaers C, et al. Ustekinumab in bio-na?ve and bio-failure Crohn’s disease patients: results from a ?real-life? monocentric cohort. Dig Liver Dis, 2021, 53(1): 72-78.
34. Adedokun OJ, Xu Z, Gasink C, et al. Population pharmacokinetics and exposure-response analyses of ustekinumab in patients with moderately to severely active Crohn’s disease. Clin Ther, 2022, 44(10): 1336-1355.
35. Dulai P, Guizzetti L, Ma T, et al. 637 clinical prediction model and decision support tool for ustekinumab in Crohn’s disease. Am J Gastroenterol, 2019, 114(1): S373-S373.
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