Efficacy and Safety of Low-Dose Upadacitinib Combined With Ustekinumab in the Treatment of Refractory Crohn's Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Clinical remission rate at Week 12 to Week 16
研究概览
简要总结
A multicenter retrospective study evaluating the effectiveness and safety of ustekinumab combined with low-dose upadacitinib in patients with refractory Crohn's disease.
详细描述
This is a multicenter, retrospective, real-world observational study conducted at several inflammatory bowel disease centers in China. The study is designed to evaluate the effectiveness and safety of ustekinumab (UST) combined with low-dose upadacitinib (UPA; 15 mg/day or 30 mg/day) in patients with moderate-to-severe active refractory Crohn's disease. Eligible patients received combination therapy between July 1, 2023 and December 31, 2025. Patients were required to have previously failed, been intolerant to, or experienced adverse events with anti-tumor necrosis factor therapy, followed by an inadequate response or intolerance to UST monotherapy or UPA 45 mg/day administered for 12 weeks. The combination regimen consisted of intravenous re-induction with UST and oral low-dose UPA at 15 mg/day or 30 mg/day for 12 weeks. Clinical response and clinical remission are assessed at weeks 12 to 16, while endoscopic response and endoscopic remission are assessed between weeks 12 and 24. Maintenance treatment after the initial 12-week combination period and safety outcomes through week 24 are also evaluated. Data are obtained retrospectively from existing medical records, and no study-specific intervention is assigned to participants.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 65 years.
- •Patients with a confirmed diagnosis of Crohn's disease according to the European Crohn's and Colitis Organisation (ECCO) criteria.
- •Patients with prior failure, loss of response, intolerance, or contraindication to anti-TNF therapy, who subsequently had inadequate response to ustekinumab or upadacitinib monotherapy between July 1, 2023 and May 31,
- •Active Crohn's disease defined by Harvey-Bradshaw Index (HBI) >4, or endoscopic disease activity with at least one segment having an SES-CD ulcer subscore ≥
- •Postoperative endoscopic recurrence was defined as modified Rutgeerts score ≥i2b. For patients in whom the small bowel anastomosis could not be reached endoscopically, disease activity was assessed by the treating physician based on clinical symptoms, elevated inflammatory markers, and imaging findings.
- •Patients who required dose reduction during full-dose upadacitinib treatment because of adverse events, or who had persistent clinical symptoms, elevated C-reactive protein, active endoscopic disease, postoperative recurrence, or active disease on imaging despite upadacitinib treatment.
- •Patients with inadequate response or loss of response to ustekinumab treatment, defined by persistent clinical symptoms, elevated C-reactive protein, active endoscopic disease, postoperative recurrence, imaging evidence of active disease, or recurrence after initial response during maintenance therapy.
- •Availability of inflammatory markers and imaging results within 3 months before initiation of combination therapy.
排除标准
- •Patients receiving upadacitinib in combination with biologics other than ustekinumab.
- •Patients receiving full-dose upadacitinib 45 mg/day in combination with ustekinumab.
- •Patients with contraindications to upadacitinib, including hypersensitivity to the active substance or excipients, active tuberculosis or severe infection, malignancy, thromboembolic events, or severe hepatic impairment.
- •Patients with severe infection, malignancy, pregnancy, or lactation.
- •Patients with severe intestinal stricture, perforation, or intra-abdominal abscess that might require surgery and interruption of drug therapy during the study period.
- •Patients considered unsuitable for the above treatment by the treating physician.
- •Patients with incomplete data, inability to complete follow-up, or loss to follow-up.
研究组 & 干预措施
Low-dose upadacitinib plus ustekinumab cohort
Patients with refractory Crohn's disease who received low-dose upadacitinib in combination with ustekinumab in a multicenter retrospective real-world cohort study.
干预措施: Ustekinumab (UST) (Drug)
Low-dose upadacitinib plus ustekinumab cohort
Patients with refractory Crohn's disease who received low-dose upadacitinib in combination with ustekinumab in a multicenter retrospective real-world cohort study.
干预措施: Upadacitinib (Drug)
结局指标
主要结局
Clinical remission rate at Week 12 to Week 16
时间窗: Week 12 to Week 16 after initiation of combination therapy
The proportion of patients achieving clinical remission at Week 12 to Week 16 after initiation of low-dose upadacitinib plus ustekinumab combination therapy. Clinical remission is defined as a Harvey-Bradshaw Index (HBI) score \<5, or clinical remission as judged by the treating physician.
次要结局
- Endoscopic healing rate at Week 12 to Week 24(Week 12 to Week 24 after initiation of combination therapy)
- Endoscopic response rate at Week 12 to Week 24(Week 12 to Week 24 after initiation of combination therapy)
研究者
Xiaolei Wang
Director
Shanghai 10th People's Hospital