A Multi-center, Open, Randomized, 18-month, Parallel-group, Superiority Study to Compare the Effect of Proactive Therapeutic Drug Monitoring Versus Standard of Care With Regards to Maintenance of Sustained Disease Control Without Flare in Adults With Rheumatoid Arthritis Treated With a Subcutaneous Tumor Necrosis Factor Inhibitor
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 387
- 试验地点
- 30
- 主要终点
- Sustained disease control over the follow-up period of 18 months without flare
研究概览
简要总结
The goal of this clinical trial is to compare therapeutic drug monitoring (TDM) versus Standard of care in patients with rheumatoid arthritis treated with a subcutaneous tumor necrosis factor inhibitor (adalimumab).
The main question it aims to answer is:
Is TDM superior to standard of care in order to maintain sustained disease control without flares?
Participants will be followed with blood sampling every second month, measuring serum drug levels and anti-drug antibodies of the TNFi. In the TDM-group, the researchers will adjust the dosage of the TNFi based on knowledge on optimal therapeutic ranges. In the Standard of care group, the TNFi will be administered according to standard of care without knowledge of serum drug levels or anti-drug antibodies.
详细描述
There is a considerable variation in serum drug levels among rheumatoid arthritis (RA) patients on tumor necrosis factor inhibitors (TNFi), and a high number develop neutralizing anti-drug antibodies (ADAb). Sub-therapeutic drug levels and ADAb formation are major contributors to TNFi treatment failure and disease flare. Proactive therapeutic drug monitoring (TDM), i.e., individualized drug dosing based on regular assessments of serum drug levels and ADAb, has the potential to optimize the efficacy and safety of TNFi treatment.
The aim of the RA-DRUM trial is to assess whether TDM is superior to standard of care in order to maintain sustained disease control without flares in patients with RA treated with the SC TNFi adalimumab.
Participants will be randomized to:
- Administration of TNFi based on proactive TDM (TDM group)
- Administration of TNFi based on standard of care without knowledge of serum drug levels or ADAb status (Standard of care group)
Participants will be followed for 18 months with on-site visits at baseline, 4, 8, 12 and 18 months and digital visits at 2, 6, 10, 14, and 16 months. Blood sampling for serum drug levels and anti-drug antibodies will be done at all visits.
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
盲法说明
The joint assessor will be blinded.
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A clinical diagnosis of RA
- •≥ 18 and under 75 years of age at screening
- •On stable therapy with standard dose of a SC TNFi (adalimumab) for a minimum of 3 months and a maximum of 24 months
- •In low disease activity or remission (DAS28-CRP under 3.2) and indication for continuation of treatment according to the treating physician
- •Subject capable of understanding and signing an informed consent form
排除标准
- •Major comorbidities, such as previous malignancies within the last 5 years, uncontrolled diabetes mellitus, severe infections (including HIV), uncontrollable hypertension, severe cardiovascular disease (NYHA class 3 or 4), severe respiratory diseases, demyelinating disease, significant chronic widespread pain syndrome, significant renal or hepatic disease, and/or other diseases or conditions which either contraindicate treatment with SC TNFi or make adherence to the protocol difficult
- •Hypersensitivity to sc TNFi (adalimumab).
- •Pregnancy, or subject considering becoming pregnant during the study period
- •Psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers, or other factors that makes adherence to the study protocol difficult
- •Changes in csDMARD co-medication, including dose changes of csDMARD or changes in the dose of corticosteroids within the last 2 months
- •Co-medication with bDMARD, tsDMARD, or other immunosuppressive drugs (excluding csDMARD and corticosteroids ≤ 7.5 mg prednisolone (or equivalent) once daily).
- •Active participation in any other interventional study.
- •In need of live vaccines during the study period.
研究组 & 干预措施
TDM-group
In the TDM-group, the TNFi dose will be adjusted in order to keep the drug level within the therapeutic range
干预措施: Therapeutic drug monitoring (TDM) of adalimumab (Drug)
Standard of Care group
In the Standard of Care group, TNFi will be administered according to standard of care without knowledge of serum drug levels or ADAb
结局指标
主要结局
Sustained disease control over the follow-up period of 18 months without flare
时间窗: 4, 8, 12, 18 months
A flare defined as either of the following: A combination of an increase in Disease Activity Score using 28 joints C-reactive protein (DAS28-CRP) ≥ 1.2, or ≥ 0.6 if DAS28-CRP ≥ 3.2, AND ≥ 2 swollen joints on examination of 44 joints OR Consensus between patient and physician that a disease flare has occurred, leading to a major change\* in treatment \*Please see protocol for the definition of a major change in treatment (due to word restrictions)
次要结局
- Disease activity assessed by Disease Activity Score using 28 joints C-reactive protein (DAS28-CRP)(4, 8, 12, and 18 months)
- Patient Global assessment of disease activity (PGA)(4, 8, 12, and 18 months)
- Disease activity measured by 44 joint count(4, 8, 12, and 18 months)
- Evaluators Global Assessment of Disease Activity (EGA)(4, 8, 12, and 18 months)
- Rheumatoid Arthritis Impact of Disease (RAID)(4, 8, 12, and 18 months)
- Occurrence of anti-drug antibodies (ADAb)(2, 4, 6, 8, 10, 12, 14, 16, 18 months)
- Serum drug levels(2, 4, 6, 8, 10, 12, 14, 16, 18 months)
- Disease activity assessed by Clinical Disease Activity Index (CDAI)(4, 8, 12, and 18 months)
- Disease activity assessed by Simple Disease Activity Index (SDAI)(4, 8, 12, and 18 months)
- Remission assessed by American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) remission criteria(4, 8, 12, and 18 months)
- Evaluation of physical function measured by Modified Health Assessment Questionnaire (MHAQ)(4, 8, 12, and 18 months)
- Number and type of adverse events (AE)(4, 8, 12, and 18 months)
- Drug survival(4, 8, 12, and 18 months)
- Drug consumption(18 months)