REDO-JAK: Dose REDuction Of JAnus Kinase Inhibitors in Patients With Inflammatory Rheumatic Diseases
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 7
- 主要终点
- The proportion of patients in low disease activity (LDA) at 12 months of follow-up in each study group.
研究概览
简要总结
The goal of this clinical trial is to assess the effectiveness of a disease activity guided dose reduction strategy of Janus kinase inhibitor (JAKi) compared to disease activity guided JAKi continuation in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) who are in a state of low disease activity or remission while on JAKi. The main question it aims to answer is:
Is a disease activity guided dose reduction strategy for JAKi not inferior in terms of efficacy compared to disease activity guided JAKi continuation in patients with RA/PsA/axSpA that are currently in a low disease activity/remission state?
Researchers will compare a disease activity guided dose reduction strategy for JAKi to disease activity guided JAKi continuation in patients with RA/PsA/axSpA that are currently in a low disease activity/remission state to see if a disease activity guided dose reduction strategy for JAKi is not inferior in terms of efficacy compared to disease activity guided JAKi continuation.
Participants will:
- Follow a JAKi dose reduction strategy or will continue using JAKi in the same dose
- Study (telemonitoring) visits are planned every 3 months
- At every visit, patients are asked to complete patient-reported outcomes that assess daily functioning, health-related quality of life, pain, fatigue, productivity loss, medical consumption and medication adherence.
详细描述
Rationale Janus kinase inhibitors (JAKi) are used in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). Despite their proven effectiveness, use of these drugs increases the risk of infections and is costly. In addition, there have been recent warnings that JAKi may increase the risk of cardiovascular disease and cancer. For other anti-rheumatic drugs, disease activity guided dose reduction has been shown to be safe and cost-effective while reducing side effects. This has not yet been studied for JAK inhibitors, while it is very relevant given the concerns regarding side effects and costs of the drugs.
Objective The primary objective of this project is to assess the effectiveness of a disease activity guided dose reduction strategy of JAKi compared to disease activity guided JAKi continuation in patients with RA, PsA and axSpA who are in a state of low disease activity or remission while on JAKi. Key secondary objectives are to assess feasibility of the proposed dose reduction strategies, safety, cost-effectiveness and the identification of possible predictive biomarkers for (un)successful dose reduction or discontinuation of JAKi.
Main trial endpoints The main trial endpoint is the non-inferiority of the difference in the proportion of people with low disease activity between the dose reduction group and the continuation group after 12 months compared to the non-inferiority margin.
Secondary trial endpoints Secondary trial endpoints include the proportion of people in the intervention group able to reduce and/or discontinue their JAKi, cost-effectiveness of the dose reduction strategy compared to the continuation strategy, and between group differences in the incidence of disease flares, difference in functioning, quality of life, pain, fatigue, safety and costs.
Trial design This open label study is a partially randomised patient preference trial, also known as a comprehensive cohort study. Participants will be randomised (2:1 ratio) to step-by-step dose reduction or continuation of standard dosing. If potential participants have a strong preference for a specific group and do not wish to be randomised, they will be given the opportunity to choose their group. Follow up for and individual patient is this trial will be 12 months.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients ≥ 16 years of age
- •Clinical diagnosis of RA, PsA or axSpA
- •Treated with a JAKi (monotherapy or combination with csDMARDwith a JAKi dose ≥ 50% of the authorised dose)
- •LDA or remission for at least 6 months according to accepted criteria for the specific disease and/or the judgement of the treating rheumatologist and patient. (RA: DAS28-CRP < 2.9; PsA: PASDAS ≤3.2 and psoriasis mBSA involvement ≤3%; axSpA: ASDAS <2.1.)
排除标准
- •Comorbidity for which continued JAKi treatment is expected to be necessary (e.g. active Crohn's disease, ulcerative colitis)
- •Life expectancy ≤12 months
- •Pregnancy (JAKi are contra-indicated during pregnancy, therefore we do not expect patients using a JAKi while pregnant)
- •Patients who are enrolled in other trials that might mutually interfere
- •Not able to provide informed consent
研究组 & 干预措施
Dose reduction group (randomised)
disease activity guided dose reduction strategy of JAKi
干预措施: JAKi dose reduction strategy (Drug)
Control group (randomised)
disease activity guided continuation of same dose strategy of JAKi (randomised)
干预措施: JAKi disease activity guided continuation of same dose strategy (Drug)
Dose reduction group (non-randomised)
disease activity guided dose reduction strategy of JAKi
干预措施: JAKi dose reduction strategy (Drug)
Control group (non-randomised)
disease activity guided continuation of same dose strategy of JAKi
干预措施: JAKi disease activity guided continuation of same dose strategy (Drug)
结局指标
主要结局
The proportion of patients in low disease activity (LDA) at 12 months of follow-up in each study group.
时间窗: At 12 months of follow-up.
The proportion of patients in low disease activity (LDA) at 12 months of follow-up in each study group. LDA is defined as DAS28-CRP \< 2.9 for RA patients, PASDAS \< 3.2 and mBSA involvement ≤3% for PsA and ASDAS \< 2.1 and an absence of active extra musculoskeletal symptoms for axSpA.
次要结局
- Mean DAS28-CRP for RA patients, PASDAS for PsA patients and ASDAS for AxSpA patients.(At 6 and 12 months of follow up.)
- Proportion of patients in intervention group at every dose reduction step.(At 6 and 12 months of follow up.)
- The proportion of patients developing adverse events in each study group.(Through study completion, an average of 12 months)
- The cumulative incidence of patients experiencing a flare.(Through study completion, an average of 12 months)
- Proportion of patients using comedication.(At baseline and through study completion, an average of 12 months)
- The incremental cost effectiveness ratio(Through study completion, an average of 12 months)
- Association between possible predictors and outcome.(Through study completion, an average of 12 months)