DISCO: DIScontinuation of COncomitant Disease Modifying Anti-rheumatic Drugs (DMARDs) in Rheumatoid Arthritis Patients Also Using TNF Inhibitors - a Randomized Long-term Non-inferiority Strategy Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 202
- 试验地点
- 4
- 主要终点
- The between-group difference in mean time-weighted DAS28-CRP during 24 months of follow-up.
研究概览
简要总结
The goal is to investigate whether a strategy of attempting to discontinue of MTX or LEF (and restart when necessary) in RA patients treated with an optimal dose (allowed dose or lower, tapered to the maximum, or according to patient preference) TNFi is not worser to a continuation of combination therapy. The study will also examine the disease-related effects of treatment that attempts to discontinue MTX or LEF, how patients experience it, its safety, and its impact on medication usage and healthcare costs.
The main outcome is the difference between treatments in average disease activity over 24 months. The study will compare whether disease activity remains similar between patients who attempt to discontinue MTX or LEF and those who continue combination therapy.
Patients will be followed for 24 months with scheduled hospital visits at baseline, after 3, 6, 12, 18, and 24 months, remote visits, and additional visits for disease flares. X-rays of the hands and feet will be taken at baseline and after 24 months. During some visits, additional blood samples will be taken to measure inflammation markers and medication levels.
详细描述
Rationale Rheumatoid arthritis (RA) is a long-term inflammatory disease that causes joint pain, swelling, and stiffness. Many patients are treated with a combination of medications to control inflammation. These usually include a biological medicine called a TNF inhibitor (TNFi) and another medicine, methotrexate (MTX) or leflunomide (LEF). Although this combination treatment is effective, patients often experience side effects (such as gastro-intestinal complaints and fatigue), require frequent blood tests, and may experience treatment fatigue from taking multiple medications. Patients would therefore prefer to reduce their medication. The safe reduction of TNFi treatment has been studied before. It is still unclear whether patients can safely discontinue MTX or LEF when their disease is well controlled. This study investigates whether attempting to discontinue MTX or LEF while using a TNF inhibitor is no worse than continuing combination treatment in terms of disease activity, with the hope of reducing side effects, the need for monitoring, and healthcare costs.
Objective The objective is to investigate whether a strategy of attempting to discontinue of MTX or LEF (and restart when necessary) in RA patients treated with an optimal dose (allowed dose or lower, tapered to the maximum, or according to patient preference) TNFi is not worser to a continuation of combination therapy. The study will also examine the disease-related effects of treatment that attempts to discontinue MTX or LEF, how patients experience it, its safety, and its impact on medication usage and healthcare costs.
Main trial endpoints The main endpoint is the difference between treatments in average disease activity over 24 months. The study will compare whether disease activity remains similar between patients who attempt to discontinue MTX or LEF and those who continue combination therapy.
Secondary trial endpoints Other study outcomes include the proportion of patients in the discontinuation strategy group using MTX/LEF and/or a TNFi after 24 months, and differences between treatments in patient-reported outcomes, joint damage measured by X-ray, blood levels of TNF inhibitors, safety and cost-effectiveness.
Trial design This study is being conducted in multiple hospitals. A total of 202 patients with RA will be randomly assigned to stopping MTX/LEF or continuation of combination therapy and followed for 24 months. Two-thirds of the patients will attempt to discontinue MTX or LEF (discontinuation group), and one-third will continue using the combination treatment (continuation group).
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
- •Age ≥ 18 years.
- •Diagnosis of RA, according to the 2010 ACR/EULAR and/or 1987 RA classification criteria or clinical diagnosis by a rheumatologist.
- •Stable disease activity for ≥ 6 months, defined as DAS28-CRP ≤ 2.9 or DAS28-CRP ≤ 3.5 combined with clinical judgment of LDA.
- •Current combination therapy consisting of TNFi and either MTX or LEF.
- •TNFi administration at a stable dose (at an optimal dose, defined as the authorized dose or lower and being maximally tapered, because of prior disease flare or patient preference) for ≥6 months prior to screening, during which LDA is maintained for ≥6 months.
- •MTX or LEF administration at a stable dose for ≥3 months prior to screening.
- •Ability to comply with all study procedures, visits and follow-up assessments.
- •Written informed consent provided prior to any study-related procedure.
排除标准
- •A previous attempt within the last 12 months prior to screening to taper or discontinue MTX or LEF that required reintroduction or dose increase of the csDMARD due to a disease flare.
- •Current MTX or LEF treatment for other indications than RA.
- •Current treatment with prednisolone (equivalent) of > 5 mg per day.
- •Current severe comorbidity or serious life-shortening condition that could interfere with adherence to the study protocol or completion of the 24-month follow-up period.
- •Women that are pregnant, breast feeding or considering pregnancy during the study period (MTX and LEF are contraindicated in pregnancy and breastfeeding).
- •Inability to comply with the study procedures, visits, or follow-up assessments.
- •Inability or unwillingness to provide informed consent.
研究组 & 干预措施
csDMARD discontinuation
Participants will discontinue their csDMARD (MTX or LEF) immediately following randomization and continue TNFi monotherapy at their current stable dose.
干预措施: Strategy to attempt discontinuation of MTX or LEF (and restart when necessary) (Drug)
csDMARD continuation
Participants will aim to continue combination therapy with csDMARD (MTX or LEF) and TNFi at their current stable doses.
干预措施: Continuation of MTX or LEF (Drug)
结局指标
主要结局
The between-group difference in mean time-weighted DAS28-CRP during 24 months of follow-up.
时间窗: At 24 months of follow-up.
The between-group difference in mean time-weighted DAS28-CRP during 24 months of follow-up. A mean time-weighted DAS28-CRP is chosen to balance the limitations of assessing disease activity at a single timepoint with solely considering the occurrence of flare. The time-weighted DAS28-CRP consists of a weighted average of a patient's DAS28-CRP scores, calculated using the trapezoid method and weighed by the time interval between measurements.
次要结局
- Between-group difference in disease activity(At 3, 6, 12, 18 and 24 months of follow-up.)
- Between-group difference at specific timepoint disease activity(At 3, 6, 12, 18 and 24 months of follow-up.)
- Between-group difference in PROM(At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.)
- Between-group difference in radiographic progression(At 24 months of follow-up.)
- Between-group difference in physical functioning(At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.)
- Between-group difference in quality of life(At baseline and 3, 6, 12, 18 and 24 months of follow-up and flare-visits.)
- Between-group difference in pharmacokinetic and immunogenicity parameters(At baseline and 3 and 24 months of follow-up.)
- Between-group difference in flares(At 24 months of follow-up.)
- Between-group difference in safety(At 24 months of follow-up.)
- Between-group difference in medication use(At 24 months of follow-up.)