Comparative effectiveness of ustekinumab vs. vedolizumab for anti-TNF-naïve or anti-TNF-exposed Crohn's disease: a multicenter cohort study

Hongsheng Yang; Zhaopeng Huang; Miao Li; Haiyan Zhang; Lingyu Fu; Xiaoling Wang; Qiaoqiao Yang; Yun He; Wenhong Wu; Taofeng Jiang; Zhimei Sun; Tao Zhang; Dongping Lai; Xixin Wu; Lishuo Shi; Qin Guo; Yanhui Wu; Jian Tang; Kang Chao; Xiang Gao

doi:10.1016/j.eclinm.2023.102337

Comparative effectiveness of ustekinumab vs. vedolizumab for anti-TNF-naïve or anti-TNF-exposed Crohn's disease: a multicenter cohort study

EClinicalMedicine. 2023 Dec 2:66:102337. doi: 10.1016/j.eclinm.2023.102337. eCollection 2023 Dec.

Authors

Hongsheng Yang^{1

2

3}, Zhaopeng Huang^{1

2

3}, Miao Li^{1

2

3}, Haiyan Zhang⁴, Lingyu Fu⁴, Xiaoling Wang⁵, Qiaoqiao Yang⁵, Yun He⁶, Wenhong Wu⁶, Taofeng Jiang⁷, Zhimei Sun⁷, Tao Zhang⁸, Dongping Lai⁸, Xixin Wu⁹, Lishuo Shi¹⁰, Qin Guo^{1

2

3

11}, Yanhui Wu^{1

2

3}, Jian Tang^{1

2

3}, Kang Chao^{1

2

3}, Xiang Gao^{1

2

3}

Affiliations

¹ Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.
² Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.
³ Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.
⁴ Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China.
⁵ Department of Nutrition, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, PR China.
⁶ Department of Gastroenterology, Liuzhou People's Hospital, Liuzhou, PR China.
⁷ Department of Gastroenterology, Meizhou People's Hospital, Meizhou, PR China.
⁸ Department of Gastroenterology, Ruikang Hospital Affiliated Guangxi University of TCM, Nanning, PR China.
⁹ Department of Systems Engineering and Engineering Management, The Chinese University of Hong Kong, Hong Kong, PR China.
¹⁰ Center of Clinical Research, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.
¹¹ Department of Small Bowel Endoscopy, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.

Abstract

Background: Ustekinumab and vedolizumab are both effective for treating Crohn's disease (CD). However, no head-to-head trials have been conducted thus far. We aimed to compare the effectiveness of ustekinumab and vedolizumab in CD patients either naïve or exposed to tumor necrosis factor-alpha inhibitors (TNFi).

Methods: Patients treated with vedolizumab or ustekinumab for luminal CD were included from six centers in China from May 2020 to July 2023. Steroid-free remission, clinical remission, objective response, and remission at Weeks 26 and 52 were evaluated in a retrospective multicenter propensity score-weighted cohort.

Findings: A total of 536 patients were included (386 ustekinumab, and 150 vedolizumab). After adjustment, ustekinumab showed higher rates of clinical remission (56.4% vs. 47.8%, P = 0.005), steroid-free remission (55.4% vs. 46.1%, P = 0.003), and objective response (67.8% vs. 42.7%, P < 0.001) than vedolizumab at Week 26. At Week 52, ustekinumab exhibited significantly higher rates of clinical remission (65.8% vs. 37.5%, P < 0.001), steroid-free remission (65.8% vs. 37.5%, P < 0.001), objective response (66.7% vs. 23.8%, P < 0.001), and objective remission (31.4% vs. 12.7%, P < 0.001). Subgroup analyses revealed that ustekinumab had higher rates of clinical remission, steroid-free remission, and objective response at Weeks 26 and 52, and objective remission at Week 52 in TNFi-exposed patients, while ustekinumab showed higher rates of objective response at Weeks 26 and 52 and clinical remission, steroid-free remission and objective remission at Week 52 in TNFi-naïve patients. Adverse event rates were similar between the groups (4.9% ustekinumab vs. 6.7% vedolizumab, P = 0.423).

Interpretation: Ustekinumab showed superior clinical and objective outcomes compared to vedolizumab, with comparable safety outcomes. The therapeutic superiority was observed in both short-term and long-term phases in TNFi-exposed patients, and the long-term phase in TNFi-naïve patients.

Funding: National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Key Research Projects of the Sixth Affiliated Hospital, Sun Yat-sen University, the program of Guangdong Provincial Clinical Research Center for Digestive Diseases, and National Key Clinical Discipline.

Keywords: Crohn’s disease; ustekinumab; vedolizumab.