DOP058 Efficacy and Safety of Vedolizumab Combined with Upadacitinib in Moderate-to-Severe Ulcerative Colitis: A Multicenter, Prospective, Randomized Controlled Trial
Authors: Wu H , Su T , Wu L , Zhi M , Yao J 
Published: January 2025

Abstract

Background
The optimal treatment strategy for moderate-to-severe ulcerative colitis (UC) remains challenging. This study aimed to evaluate the efficacy and safety of combination therapy with vedolizumab (VDZ) plus upadacitinib (UPA) compared to VDZ monotherapy.

Methods
In this multicenter, prospective, randomized controlled trial, patients with moderate-to-severe UC were randomized to receive either VDZ (300mg at weeks 0, 2, 6, then every 8 weeks through week 54) plus UPA (45mg daily for 8 weeks) or VDZ monotherapy. Primary endpoints included clinical response, sustained clinical response, clinical remission, sustained clinical remission, and CRP normalization at weeks 8 and 54. Secondary endpoints included endoscopic response, sustained endoscopic response, endoscopic remission, sustained endoscopic remission and quality of life changes.

Results
61 patients were enrolled (combination therapy: n=26; monotherapy: n=35). At week 8, the combination therapy group showed significantly higher clinical response rates compared to the monotherapy group (63.4% vs 34.3%, P=0.037). Clinical remission rates were 30.8% vs 11.4% (P=0.152). Endoscopic response rates were significantly higher in the combination group (61.5% vs 40.0%, P=0.042). Endoscopic remission (46.2% vs 25.7%, P=0.209), and histological remission (34.6% vs 14.3%, P=0.157) showed numerical improvements. Laboratory inflammatory markers and nutritional parameters improved in both groups without significant between-group differences.

Conclusion
Conclusions: VDZ plus UPA combination therapy showed better early clinical and endoscopic outcomes compared to VDZ monotherapy in moderate-to-severe UC. Both treatments improved inflammatory and nutritional markers. This dual-targeted approach may represent a promising treatment strategy for UC patients, though larger studies with longer follow-up are needed to confirm these findings.

References
1.Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017;390(10114):2769-2778.
2.Kaplan GG. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol. 2015;12(12):720-727.
3.Ahuja D, Murad MH, Ma C, Jairath V, Singh S. Comparative Speed of Early Symptomatic Remission with Advanced Therapies for Moderate-Severe Ulcerative Colitis: A Systematic Review and Network Meta-Analysis. Am J Gastroenterol. 2023.
4.Zhang S, Chen B, Wang B, et al. Effect of Induction Therapy With Olamkicept vs Placebo on Clinical Response in Patients With Active Ulcerative Colitis: A Randomized Clinical Trial. JAMA. 2023;329(9):725-734.
5.Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD. ACG Clinical Guideline: Ulcerative Colitis in Adults. Am J Gastroenterol. 2019;114(3):384-413.
6.Feuerstein JD, Isaacs KL, Schneider Y, et al. AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis. Gastroenterology. 2020;158(5):1450-1461.
7.Ardizzone S, Cassinotti A, Duca P, et al. Mucosal healing predicts late outcomes after the first course of corticosteroids for newly diagnosed ulcerative colitis. Clin Gastroenterol Hepatol. 2011;9(6):483-489 e483.
8.Card T, Ungaro R, Bhayat F, Blake A, Hantsbarger G, Travis S. Vedolizumab use is not associated with increased malignancy incidence: GEMINI LTS study results and post-9.marketing data. Aliment Pharmacol Ther. 2020;51(1):149-157.
9.Colombel JF, Sands BE, Rutgeerts P, et al. The safety of vedolizumab for ulcerative colitis and Crohn's disease. Gut. 2017;66(5):839-851.
10.Colombel JF, Sands BE, Rutgeerts P, et al. The safety of vedolizumab for ulcerative colitis and Crohn's disease. Gut. 2017;66(5):839-851.
11.Sandborn WJ, Baert F, Danese S, et al. Efficacy and Safety of Vedolizumab Subcutaneous Formulation in a Randomized Trial of Patients With Ulcerative Colitis.
12.Sands BE, Peyrin-Biroulet L, Loftus EV, Jr., et al. Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis. N Engl J Med. 2019;381(13):1215-1226.Gastroenterology. 2020;158(3):562-572 e512.
13.Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet. 2022;399(10341):2113-2128.