Safety and Efficacy of a STOPping Strategy Versus Classical Maintenance Dose of JAK Inhibitors in Deep Remission Patients With Ulcerative Colitis: a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 224
- 试验地点
- 22
- 主要终点
- The primary endpoint of this study will be a composite criterion of treatment safety, efficacy, and patient satisfaction during the first 52 weeks of the follow-up.
研究概览
简要总结
This phase IV, multicenter, open-label randomized controlled trial will evaluate whether a JAK inhibitor discontinuation strategy is superior to standard maintenance therapy in adult patients with ulcerative colitis who are in sustained deep remission. A total of 224 patients treated with tofacitinib, upadacitinib, or filgotinib will be randomized to either treatment withdrawal or continuation of maintenance therapy and followed for 104 weeks. The primary objective is to compare safety, efficacy, and patient satisfaction at Week 52, while secondary objectives include assessment of remission maintenance, quality of life, treatment exposure, endoscopic outcomes, and relapse rates
详细描述
Background:
Janus kinase (JAK) inhibitors are effective oral therapies for moderate-to-severe ulcerative colitis (UC). Their lack of immunogenicity provides a unique opportunity to evaluate treatment withdrawal and intermittent treatment strategies. However, safety concerns raised by regulatory agencies, including increased risks of infections, venous thromboembolism, major adverse cardiovascular events, and malignancies, support the investigation of strategies aiming to reduce long-term exposure to JAK inhibitors while maintaining disease control.
Objective:
To demonstrate the superiority of a JAK inhibitor stopping strategy compared with standard maintenance therapy in terms of treatment safety, efficacy, and patient satisfaction in adults with ulcerative colitis in deep remission.
Study Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of UC from at least 6 months according to clinical, endoscopic, histological and/or radiological criteria.
- •Male or female age ≥ 18 years
- •Currently treated by JAK inhibitor (tofacitinib, upadacitinib or filgotinib) for more than 12 months.
- •Currently at a stable dose of tofacitinib (5mg or 10mg twice a day), upadacitinib (15mg or 30mg per day) or filgotinib (200mg per day) for 6 months.
- •Clinical steroid free remission for at least 6 months, defined by a partial Mayo Score < 2, with no subscore > 1 and rectal bleeding (RB) subscore of 0 (annex 1).
- •Endoscopic steroid free remission for at inclusion, defined by a Mayo endoscopic subscore = 0 (annex 1).
- •Fecal calprotectin ≤ 150μg/g.
- •Without known risk factors for venous thromboembolism (VTE).
- •Without known risk factors for major adverse cardiovascular events (MACE).
- •Without known risk factors for malignancy.
- •For women of child-bearing potential (WOCBP), and for men with partners who are WOCBP, willingness to use appropriate and efficient contraception, as recommended when using JAK inhibitor treatment (notably upadacitinib), during all the experimental treatment and until at least 4 weeks after the end of the experimental treatment, according to SmPC and CTFG (Clinical Trials Facilitation and Coordination Group) recommendations.
- •Patients able to understand information provide to them and to give written informed consent for study.
- •Affiliation to a social security scheme.
- •Good general health according to history and clinical examination.
排除标准
- •Steroid use ≤ 6 months prior to enrolment.
- •Currently treated by steroid, immunosuppressive agents or biologics.
- •Pregnancy or planned pregnancy during the study.
- •Breastfeeding.
- •Non-compliant subject or inability to follow study protocol.
- •Intolerance of JAK inhibitors (excipients included) or severe adverse event.
- •Contraindications to using a JAK inhibitor (excipients included).
- •Known risk factors for VTE.
- •Known risk factors for MACE.
- •Active neoplasia or history of malignant tumours less than 5 years old.
- •Participation to another interventional study protocol (except for RIPH3 studies)
- •Severe hepatic insufficiency.
- •Severe to end-stage renal insufficiency.
- •Active tuberculosis, serious infections such as septicemia or opportunistic infections.
- •Absence or refusal of informed consent.
- •People under guardianship, conservatorship, or judicial protection;
- •People receiving psychiatric care;
- •People who have been deprived of their liberty by judicial or administrative order
- •People with difficulty understanding and/or cognitive disorder
结局指标
主要结局
The primary endpoint of this study will be a composite criterion of treatment safety, efficacy, and patient satisfaction during the first 52 weeks of the follow-up.
时间窗: 1 year
treatment safety, during the first 52 weeks of the follow-up.
次要结局
- Assess the treatment success of this innovative therapeutic strategy at the end of the first 52 weeks of the follow-up and after 104 weeks of follow-up.(2 years)
- Partial Mayo score at each visit of the entire follow-up(2 years)
- Number of days under treatment and cumulative dose of treatment per patient between randomization and primary endpoint(1 year)
- Number of days under induction dose of JAK inhibitor at the end the first 52 weeks of the follow-up.(1 year)
- Mayo endoscopic subscore at week 52 and week 104(2 years)
- Proportion of patients relapsing for each arm(2 years)
- Safety: occurrence of herpes zoster, infection, cardiovascular event, biochemical parameter, malignancies, adverse event leading to discontinuation, and all adverse events (serious or not) during the whole follow-up.(2 years)
- Remission rate at the end the first 52 weeks of the follow-up(1 year)