Objectives: Upadacitinib (UPA) and vedolizumab (VDZ) have been approved to treat moderate-to-severe ulcerative colitis (UC); however, direct comparative data between these two regimens are lacking. We aimed to compare the effectiveness and safety of UPA and VDZ among patients with moderate-to-severe UC who had previously been treated with advanced therapies.
Methods: Patients with moderate-to-severe UC receiving VDZ or UPA for at least 14 weeks following advanced therapy failure, including at least one anti-tumor necrosis factor (TNF) agent, between 2015 and 2024, were retrospectively recruited. Clinical response and remission were defined by the Partial Mayo Score and the Simple Clinical Colitis Activity Index. The safety profile during the treatment was also compared.
Results: Altogether 66 patients treated with VDZ and 22 patients with UPA were included. The median age of the VDZ and UPA groups was 38 and 37 years, respectively. Patients receiving UPA achieved significantly higher rates of corticosteroid-free remission after 52-week therapy (75.0% vs. 25.0%; adjusted odds ratio [aOR] 5.68, 95% confidence interval [CI] 1.50–21.00, p = 0.011); however, these patients were more likely to experience adverse events (AEs) (40.9% vs. 9.1%; aOR 4.60, 95% CI 1.20–17.00, p = 0.02), although medication discontinuation due to AEs was only noted in two (3.0%) patients receiving VDZ. No patients were hospitalized during the treatment period.
Conclusion: UC patients receiving UPA achieved significantly higher rates of corticosteroid-free clinical remission but with more AEs, suggesting that decision-making based on disease severity and comorbidities can help guide the positioning of these therapies in UC.
| [1] |
T. Raine, S. Bonovas, J. Burisch, et al., “ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment,” Journal of Crohn's & Colitis 16, no. 1 (2022): 2–17.
|
| [2] |
T. Wyant, E. Fedyk, and B. Abhyankar, “An Overview of the Mechanism of Action of the Monoclonal Antibody Vedolizumab,” Journal of Crohn's & Colitis 10, no. 12 (2016): 1437–1444.
|
| [3] |
J. M. Parmentier, J. Voss, C. Graff, et al., “In Vitro and in Vivo Characterization of the JAK1 Selectivity of Upadacitinib (ABT-494),” BMC Rheumatology 2 (2018): 23, https://doi.org/10.1186/s41927-018-0031-x.
|
| [4] |
B. E. Sands, L. Peyrin-Biroulet, E. V. Loftus, Jr., et al., “Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis,” New England Journal of Medicine 381, no. 13 (2019): 1215–1226.
|
| [5] |
W. Reinisch, G. Y. Melmed, H. Nakase, et al., “Comparative Efficacy and Safety of Upadacitinib vs. Vedolizumab, Ustekinumab, and Tofacitinib After Induction and Maintenance for Ulcerative Colitis: Three Matching-Adjusted Indirect Comparisons,” Advances in Therapy 41, no. 10 (2024): 3832–3849.
|
| [6] |
A. N. Ananthakrishnan, M. H. Murad, F. I. Scott, et al., “Comparative Efficacy of Advanced Therapies for Management of Moderate-To-Severe Ulcerative Colitis: 2024 American Gastroenterological Association Evidence Synthesis,” Gastroenterology 167, no. 7 (2024): 1460–1482.
|
| [7] |
N. E. Burr, D. J. Gracie, C. J. Black, and A. C. Ford, “Efficacy of Biological Therapies and Small Molecules in Moderate to Severe Ulcerative Colitis: Systematic Review and Network Meta-Analysis,” Gut 71, no. 10 (2022): 1976–1987.
|
| [8] |
J. S. Lasa, P. A. Olivera, S. Danese, and L. Peyrin-Biroulet, “Efficacy and Safety of Biologics and Small Molecule Drugs for Patients With Moderate-To-Severe Ulcerative Colitis: A Systematic Review and Network Meta-Analysis,” Lancet Gastroenterology & Hepatology 7, no. 2 (2022): 161–170.
|
| [9] |
W. J. Sandborn, F. Baert, S. Danese, et al., “Efficacy and Safety of Vedolizumab Subcutaneous Formulation in a Randomized Trial of Patients With Ulcerative Colitis,” Gastroenterology 158, no. 3 (2020): 562–572.e12.
|
| [10] |
T. Straatmijer, V. B. C. Biemans, M. Visschedijk, et al., “Superior Effectiveness of Tofacitinib Compared to Vedolizumab in Anti-TNF-experienced Ulcerative Colitis Patients: A Nationwide Dutch Registry Study,” Clinical Gastroenterology and Hepatology 21, no. 1 (2023): 182–191.e2.
|
| [11] |
B. Barberio, F. Zingone, L. Frazzoni, et al., “Real-Life Comparison of Different Anti-TNF Biologic Therapies for Ulcerative Colitis Treatment: A Retrospective Cohort Study,” Digestive Diseases 39, no. 1 (2021): 16–24.
|
| [12] |
R. S. Dalal, G. Kallumkal, H. J. Cabral, E. L. Barnes, and J. R. Allegretti, “One-Year Comparative Effectiveness of Upadacitinib vs Tofacitinib for Ulcerative Colitis: A Multicenter Cohort Study,” American Journal of Gastroenterology 119, no. 8 (2024): 1628–1631.
|
| [13] |
S. Singh, J. R. Allegretti, S. M. Siddique, and J. P. Terdiman, “AGA Technical Review on the Management of Moderate to Severe Ulcerative Colitis,” Gastroenterology 158, no. 5 (2020): 1465–1496.e17.
|
| [14] |
H. H. Herfarth, A. Afzali, M. Fischer, et al., “Clinical Long-Term Outcomes of Patient-Reported Outcomes in the Prospective Real-World Tofacitinib Response in Ulcerative Colitis Registry,” Clinical and Translational Gastroenterology 15, no. 3 (2023): e00669, https://doi.org/10.14309/ctg.0000000000000669.
|
| [15] |
D. Hirayama, S. Motoya, T. Ashida, et al., “Effectiveness and Factors Associated with Response to Golimumab in Japanese Patients with Ulcerative Colitis in Real Clinical Practice: The Phoenix Study,” Inflammatory Intestinal Diseases 8, no. 3 (2023): 115–127.
|
| [16] |
S. Akiyama, K. Yokoyama, S. Yagi, et al., “Efficacy and Safety of Filgotinib for Ulcerative Colitis: A Real-World Multicenter Retrospective Study in Japan,” Alimentary Pharmacology & Therapeutics 59, no. 11 (2024): 1413–1424.
|
| [17] |
B. Gros and G. G. Kaplan, “Ulcerative Colitis in Adults: A Review,” JAMA 330, no. 10 (2023): 951–965.
|
| [18] |
M. Benucci, A. Damiani, M. Infantino, et al., “Cardiovascular Safety, Cancer and Jak-Inhibitors: Differences to Be Highlighted,” Pharmacological Research 183 (2022): 106359, https://doi.org/10.1016/j.phrs.2022.106359.
|
| [19] |
P. A. Olivera, J. S. Lasa, S. Bonovas, S. Danese, and L. Peyrin-Biroulet, “Safety of Janus Kinase Inhibitors in Patients With Inflammatory Bowel Diseases or Other Immune-Mediated Diseases: A Systematic Review and Meta-Analysis,” Gastroenterology 158, no. 6 (2020): 1554–1573.e12.
|
| [20] |
S. Friedberg, D. Choi, T. Hunold, et al., “Upadacitinib Is Effective and Safe in Both Ulcerative Colitis and Crohn's Disease: Prospective Real-World Experience,” Clinical Gastroenterology and Hepatology 21, no. 7 (2023): 1913–1923.e2.
|
| [21] |
R. Panaccione, E. B. Collins, G. Y. Melmed, et al., “Efficacy and Safety of Advanced Therapies for Moderately to Severely Active Ulcerative Colitis at Induction and Maintenance: An Indirect Treatment Comparison Using Bayesian Network Meta-analysis,” Crohn's & Colitis 360 5, no. 2 (2023): otad009, https://doi.org/10.1093/crocol/otad009.
|
RIGHTS & PERMISSIONS
2025 The Author(s). Journal of Digestive Diseases published by Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.
PDF
