REmission in Rheumatoid Arthritis - Assessing WIthrawal of Disease-modifying Antirheumatic Drugs in a Non-inferiority Design
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 320
- 试验地点
- 10
- 主要终点
- Proportion of patients who are non-failures (have not experienced a flare)
研究概览
简要总结
The purpose of this study is to assess the effect of disease-modifying anti-rheumatic drugs (DMARDs) dose reduction in patients with rheumatoid arthritis (RA).
Remission is the treatment target in RA, but knowledge about the best way to treat RA patients who achieve sustained remission is limited. DMARDs have potential serious adverse events, and biologic DMARDs are costly to the society. The objectives for ARCTIC REWIND are to assess the effect of tapering and withdrawal of DMARDs on disease activity in RA patients in sustained remission, to study predictors for successful tapering and withdrawal of DMARDs in this patient group, and to study cost-effectiveness of different treatment options in RA remission.
ARCTIC REWIND is a randomized, open, controlled, parallel-group, multicenter, phase IV, non-inferiority strategy study. Patients with less than five years of disease duration and stable remission for at least 12 months are randomized to either continued stable treatment or tapering and withdrawal of DMARDs, including tumor necrosis factor (TNF) inhibitors and synthetic DMARDs. Patients are assessed by clinical examination, patient reported outcome measures, ultrasonography, MRI and X-ray, and monitored for adverse events. The primary endpoint of the study is the proportion of patients who are non-failures (have not experienced a flare) at 12 months. Secondary endpoints include composite disease activity scores and remission criteria, joint damage and inflammation assessed by various imaging modalities, work participation, health care resource use and health related quality of life.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Rheumatoid arthritis according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria
- •Male or non-pregnant, non-nursing female
- •>18 years of age and <80 years of age
- •Patient in the TNF-inhibitor group: Any disease duration. Patient in the synthetic DMARD group: RA diagnosis after 01.01.
- •Sustained remission for ≥12 months according to DAS or Disease Activity Score based on 28 joints (DAS28), with documented remission status at a minimum of 2 consecutive visits during the last 18 months OR participation in the first ARCTIC trial
- •DAS <1.6 and no swollen joints at inclusion OR participation in the first ARCTIC trial
- •Unchanged treatment with TNF inhibitors and/or synthetic DMARDs during the previous 12 months, with a stable or reduced dose of glucocorticosteroids OR participation in the first ARCTIC trial
- •Subject capable of understanding and signing an informed consent form
- •Provision of written informed consent
排除标准
- •Abnormal renal function, defined as serum creatinine >142 μmol/L in female and >168 μmol/L in male, or a glomerular filtration rate (GFR) <40 mL/min/1.73 m2
- •Abnormal liver function (defined as aspartate transaminase (ASAT)/alanine aminotransferase (ALAT) >3x upper normal limit), active or recent hepatitis, cirrhosis
- •Major co-morbidities, such as severe malignancies, severe diabetic mellitus, severe infections, uncontrollable hypertension, severe cardiovascular disease (NYHA class 3 or 4) and/or severe respiratory diseases
- •Leukopenia and/or thrombocytopenia
- •Inadequate birth control, pregnancy, and/or breastfeeding
- •Indications of active tuberculosis
- •Psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers or other factors which makes adherence to the study protocol impossible.
研究组 & 干预措施
Stable dose TNF inhibitor
Stable dose TNF inhibitor. Any co-medication with synthetic DMARDs kept stable.
干预措施: TNF inhibitors (Drug)
Stepdown and withdrawal of TNF inhibitor
Half-dose of TNF inhibitor for the first four months, thereafter withdrawal of TNF inhibitor. Any co-medication with synthetic DMARDs kept stable.
干预措施: TNF inhibitors (Drug)
Stable dose synthetic DMARD
Stable dose of synthetic DMARDs, either monotherapy or combination therapy.
干预措施: Synthetic DMARD(s) (Drug)
Synthetic DMARD dose reduction
Half-dose synthetic DMARDs (monotherapy or combination therapy) for the first 12 months of the study. Patients classified as non-failures are re-randomized at 12 months to either continue half-dose synthetic DMARD(s) or withdraw all DMARD(s).
干预措施: Synthetic DMARD(s) (Drug)
ARCTIC follow-up
Patients are treated according to the ARCTIC treatment schedule based on disease activity.
干预措施: TNF inhibitors (Drug)
ARCTIC follow-up
Patients are treated according to the ARCTIC treatment schedule based on disease activity.
干预措施: Synthetic DMARD(s) (Drug)
结局指标
主要结局
Proportion of patients who are non-failures (have not experienced a flare)
时间窗: 12 months
Flare is defined as composite measure: (1) An increase in disease activity score (DAS) to \>1.6 AND (2) a change in DAS of at least 0.6 AND (3) \> 1 swollen joint. If a patient does not fulfill this formal definition, but experiences a clinically significant flare according to the investigator and patient, this is treated as a flare.
次要结局
- Disease Activity Score in 28 joints (DAS28)(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Disease Activity Score (DAS)(12 months, with subsequent long-term analyses after 24 months and 36 months)
- C-reactive protein (CRP)(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Patient's assessment of disease activity (PGA)(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Health Assessment Questionnaire (HAQ-PROMIS)(12 months, with subsequent long-term analyses after 24 months and 36 months)
- EuroQol-5 Dimension (EQ-5D)(12 months, with subsequent long-term analyses after 24 months and 36 months)
- DAS-remission(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Simplified Disease Activity Index (SDAI)(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Physician's global assessment of disease avtivity (PHGA)(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Medical Outcomes Study Short-Form 36-item (SF-36) Physical and Mental Component Summary Score(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Work performance(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Clinical Disease Activity Index (CDAI)(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Swollen joint count(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Erythrocyte Sedimentation Rate (ESR)(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Tender joint count(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Radiographic joint damage(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Ultrasonography (subclinical synovitis)(12 months, with subsequent long-term analyses after 24 months and 36 months)
- DAS28-remission(12 months, with subsequent long-term analyses after 24 months and 36 months)
- SDAI-remission(12 months, with subsequent long-term analyses after 24 months and 36 months)
- CDAI-remission(12 months, with subsequent long-term analyses after 24 months and 36 months)
- ACR/EULAR Boolean remission(12 months, with subsequent long-term analyses after 24 months and 36 months)
- No swollen joint(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Radiographic outcome(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Ultrasound outcome(12 months, with subsequent long-term analyses after 24 months and 36 months)
- American College of Rheumatology (ACR) response(12 months, with subsequent long-term analyses after 24 months and 36 months)
- The European League Against Rheumatism (EULAR) response(12 months, with subsequent long-term analyses after 24 months and 36 months)
- The Food and Drug Administration (FDA) major clinical response(12 months, with subsequent long-term analyses after 24 months and 36 months)
- Medication(12 months, with subsequent long-term analyses after 24 months and 36 months)
研究者
Espen A. Haavardsholm, MD PhD
MD PhD, Head of Department
Diakonhjemmet Hospital