Sustained Treatment Success With Ustekinumab in Symptomatic Stricturing Crohn's Disease: A Retrospective Single-Arm Observational Cohort Study

Abstract

Despite being a common complication of Crohn's disease (CD), evidence regarding the use of ustekinumab (UST) for treating symptomatic strictures in China remains limited. This study evaluated the effectiveness of UST in this population and identified the predictors of successful therapy. This cohort study enrolled adults with CD initiating UST therapy for symptomatic strictures confirmed by endoscopy or imaging. The primary outcome at Week 52 was continued UST therapy without prohibited adjunctive treatments. A clinical prediction model was developed, and its performance was evaluated for identifying baseline factors associated with treatment success. Of the 73 patients screened between June 2022 and April 2024, 54 were included. At Week 52, 44 (81.5%) achieved treatment success, with most demonstrating improvements in obstructive symptom score, CD Activity Index (CDAI), endoscopic and computed tomography enterography (CTE) findings, and biochemical parameters. Nonsmoking status and C-reactive protein (CRP) levels predicted treatment success, with the model demonstrating 86.4% discriminative ability. No severe adverse events were reported, except for one case of leukemia (2%) and two cases of serious infections (4%). The study highlighted that UST effectively alleviated intestinal strictures in CD, with most patients achieving symptom remission, improved stricture morphology, and reduced inflammation.

Keywords

crohn's disease / observational cohort study / real-world study / symptomatic strictures / ustekinumab

References

[1] J. Satsangi, M. S. Silverberg, S. Vermeire, and J. F. Colombel, “The Montreal Classification of Inflammatory Bowel Disease: Controversies, Consensus, and Implications,” Gut 55, no. 6 (2006): 749–753.

[2] S. Bharadwaj, P. Fleshner, and B. Shen, “Therapeutic Armamentarium for Stricturing Crohn's Disease: Medical Versus Endoscopic Versus Surgical Approaches,” Inflammatory Bowel Diseases 21, no. 9 (2015): 2194–2213.

[3] F. Rieder, G. Latella, F. Magro, et al., “European Crohn's and Colitis Organisation Topical Review on Prediction, Diagnosis and Management of Fibrostenosing Crohn's Disease,” Journal of Crohn's and Colitis 10, no. 8 (2016): 873–885.

[4] J. Cosnes, C. Gower-Rousseau, P. Seksik, and A. Cortot, “Epidemiology and Natural History of Inflammatory Bowel Diseases,” Gastroenterology 140, no. 6 (2011): 1785–1794.e4.

[5] C. Lu, S. D. Holubar, and F. Rieder, “How I Approach the Management of Stricturing Crohn's Disease,” Official Journal of the American College of Gastroenterology 114, no. 8 (2019): 1181–1184.

[6] Y. Bouhnik, F. Carbonnel, D. Laharie, et al., “Efficacy of Adalimumab in Patients With Crohn's Disease and Symptomatic Small Bowel Stricture: A Multicentre, Prospective, Observational Cohort (CREOLE) Study,” Gut 67, no. 1 (2018): 53.

[7] F. Zorzi, S. Zuzzi, S. Onali, et al., “Efficacy and Safety of Infliximab and Adalimumab in Crohn's Disease: A Single Centre Study,” Alimentary Pharmacology & Therapeutics 35, no. 12 (2012): 1397–1407.

[8] S.-N. Lin, R. Mao, C. Qian, et al., “Development of Antifibrotic Therapy for Stricturing Crohn's Disease: Lessons From Randomized Trials in Other Fibrotic Diseases,” Physiological Reviews 102, no. 2 (2022): 605–652.

[9] G. Feagan Brian, J. Sandborn William, C. Gasink, et al., “Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease,” New England Journal of Medicine 375, no. 20 (2016): 1946–1960.

[10] A. M. Johnson, M. Barsky, W. Ahmed, et al., “The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium,” Official Journal of the American College of Gastroenterology 118, no. 2 (2023): 317–328.

[11] P. W. A. Thomas, M. van Caem, R. L. West, et al., “Long-Term Effectiveness and Safety of Ustekinumab in Crohn's Disease: A Prospective Cohort Study,” European Journal of Gastroenterology & Hepatology 35, no. 3 (2023): 261–269.

[12] K. Murate, M. Nakamura, T. Yamamura, et al., “Ustekinumab Is Effective Against Small Bowel Lesions in Crohn's Disease: Two Case Reports,” Clinical Journal of Gastroenterology 14, no. 1 (2021): 129–135.

[13] A. Elmoursi, T. A. Barrett, and C. Perry, “Double Biologic Therapy for Refractory Stricturing Crohn's Disease: A Successful Case of Deep Remission With Ustekinumab and Vedolizumab,” Inflammatory Bowel Diseases 26, no. 7 (2020): e62–e63.

[14] D. Bettenworth, M. E. Baker, J. G. Fletcher, et al., “A Global Consensus on the Definitions, Diagnosis and Management of Fibrostenosing Small Bowel Crohn's Disease in Clinical Practice,” Nature Reviews Gastroenterology & Hepatology 21, no. 8 (2024): 572–584.

[15] F. Rieder and C. Fiocchi, “Intestinal Fibrosis in IBD—A Dynamic, Multifactorial Process,” Nature Reviews Gastroenterology & Hepatology 6, no. 4 (2009): 228–235.

[16] J. Adler, D. R. Punglia, J. R. Dillman, et al., “Computed Tomography Enterography Findings Correlate With Tissue Inflammation, Not Fibrosis in Resected Small Bowel Crohn's Disease,” Inflammatory Bowel Diseases 18, no. 5 (2012): 849–856.

[17] M. Zappa, C. Stefanescu, D. Cazals-Hatem, et al., “Which Magnetic Resonance Imaging Findings Accurately Evaluate Inflammation in Small Bowel Crohn's Disease? A Retrospective Comparison With Surgical Pathologic Analysis,” Inflammatory Bowel Diseases 17, no. 4 (2011): 984–993.

[18] J. D. Schulberg, E. K. Wright, B. A. Holt, et al., “Intensive Drug Therapy Versus Standard Drug Therapy for Symptomatic Intestinal Crohn's Disease Strictures (STRIDENT): An Open-Label, Single-Centre, Randomised Controlled Trial,” Lancet Gastroenterology & Hepatology 7, no. 4 (2022): 318–331.

[19] I. Rodríguez-Lago, J. Del Hoyo, A. Pérez-Girbés, et al., “Early Treatment With Anti-Tumor Necrosis Factor Agents Improves Long-Term Effectiveness in Symptomatic Stricturing Crohn's Disease,” United European Gastroenterology Journal 8, no. 9 (2020): 1056–1066.

[20] D. Bettenworth, A. Bokemeyer, M. Baker, et al., “Assessment of Crohn's Disease-Associated Small Bowel Strictures and Fibrosis on Cross-Sectional Imaging: A Systematic Review,” Gut 68, no. 6 (2019): 1115.

[21] F. Rieder, P. K. Mukherjee, W. J. Massey, Y. Wang, and C. Fiocchi, “Fibrosis in IBD: From Pathogenesis to Therapeutic Targets,” Gut 73, no. 5 (2024): 854.

[22] N. C. Henderson, F. Rieder, and T. A. Wynn, “Fibrosis: From Mechanisms to Medicines,” Nature 587, no. 7835 (2020): 555–566.

[23] C. A. Steiner, J. A. Berinstein, J. Louissaint, et al., “Biomarkers for the Prediction and Diagnosis of Fibrostenosing Crohn's Disease: A Systematic Review,” Clinical Gastroenterology and Hepatology 20, no. 4 (2022): 817–846.e10.

[24] V. B. C. Biemans, A. E. van der Meulen-de Jong, C. J. van der Woude, et al., “Ustekinumab for Crohn's Disease: Results of the ICC Registry, a Nationwide Prospective Observational Cohort Study,” Journal of Crohn's and Colitis 14, no. 1 (2020): 33–45.

[25] C. Ma, R. N. Fedorak, G. G. Kaplan, et al., “Long-Term Maintenance of Clinical, Endoscopic, and Radiographic Response to Ustekinumab in Moderate-to-Severe Crohn's Disease: Real-World Experience From a Multicenter Cohort Study,” Inflammatory Bowel Diseases 23, no. 5 (2017): 833–839.

[26] A. Gustavsson, A. Magnuson, B. Blomberg, M. Andersson, J. Halfvarson, and C. Tysk, “Smoking Is a Risk Factor for Recurrence of Intestinal Stricture After Endoscopic Dilation in Crohn's Disease,” Alimentary Pharmacology & Therapeutics 37, no. 4 (2013): 430–437.

[27] S. Lee, M. E. Kuenzig, A. Ricciuto, et al., “Smoking May Reduce the Effectiveness of Anti-TNF Therapies to Induce Clinical Response and Remission in Crohn's Disease: A Systematic Review and Meta-Analysis,” Journal of Crohn's and Colitis 15, no. 1 (2021): 74–87.

[28] Y.-C. Ma, L. Lin, Z. Luo, and T. Jin, “Smoking Is an Independent Risk Factor for Stricture Recurrence After the Urethroplasty: A Systematic Review and Meta-Analysis,” International Brazilian Journal of Urology 49 (2023): 8–23.

[29] L. S. Kiss, T. Szamosi, T. Molnar, et al., “Early Clinical Remission and Normalisation of CRP Are the Strongest Predictors of Efficacy, Mucosal Healing and Dose Escalation During the First Year of Adalimumab Therapy in Crohn's Disease,” Alimentary Pharmacology & Therapeutics 34, no. 8 (2011): 911–922.

[30] T. Straatmijer, V. B. C. Biemans, F. Hoentjen, et al., “Ustekinuma B for Crohn's Disease: Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, a Nationwide Prospective Observational Cohort Study,” Journal of Crohn's and Colitis 15, no. 11 (2021): 1920–1930.

[31] S. K. Vuyyuru, B. Kante, P. Kumar, et al., “Real World Analysis on the Efficacy and Safety of Anti-Tumor Necrosis Factor Therapy in Patients With Stricturing Crohn's Disease,” Scientific Reports 11, no. 1 (2021): 11704.

[32] A. Dignass, G. Van Assche, J. O. Lindsay, et al., “The Second European Evidence-Based Consensus on the Diagnosis and Management of Crohn's Disease: Current Management,” Journal of Crohn's and Colitis 4, no. 1 (2010): 28–62.

[33] F. Rieder, D. Bettenworth, C. Ma, et al., “An Expert Consensus to Standardise Definitions, Diagnosis and Treatment Targets for Anti-Fibrotic Stricture Therapies in Crohn's Disease,” Alimentary Pharmacology & Therapeutics 48, no. 3 (2018): 347–357.

[34] B. Dane, J. R. Dillman, J. Fidler, et al., “SAR Consensus Recommendations for Defining Small Bowel Crohn Disease Strictures at CT and MR Enterography,” Radiology 316, no. 1 (2025): e243123.

[35] J. Kondrup, S. P. Allison, M. Elia, B. Vellas, and M. Plauth, “ESPEN Guidelines for Nutrition Screening,” Clinical Nutrition 22, no. 4 (2003): 415–421.

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