Effectiveness of a Combination of Methotrexate and a Step Down Glucocorticoid Regimen (COBRA-Slim) for Remission Induction in Patients With Early Rheumatoid Arthritis (RA), With or Without Fast Access to 24 Weeks of Tumor Necrosis Factor (TNF) Blockade in Insufficient Responders, a Randomized, Multicenter, Pragmatic Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 276
- 试验地点
- 19
- 主要终点
- Area Under Curve (AUC) of Disease Activity Score Based on a 28 Jointcount and C-reactive Protein (DAS28CRP)
研究概览
简要总结
In the Care in Rheumatoid Arthritis (CareRA) trial (NCT01172639) about 70% of early RA patients are in remission at the 2 year evaluation point independent of the combination scheme used.
Interesting to see is that the 30% of insufficient responders can be identified in an early stage of the treatment course.
The purpose of the present study is to investigate if, for patients with an insufficient response to a COBRA-Slim regimen, accelerated access to a short course of anti-TNF therapy already early after treatment initiation (from w8 until w32) could improve outcomes compared to a more traditional treat to target sequence.
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 and older
- •Diagnosis of RA as defined by the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) 2010 criteria for early RA
- •Early RA defined by a diagnosis made ≤ 1 year ago.
- •Use a reliable method of contraception for women of childbearing potential to be evaluated as in daily clinical practice
- •Able and willing to give written informed consent and to participate in the study
- •Understanding and able to write Dutch or French
排除标准
- •Previous treatment with:
- •Methotrexate (MTX) or leflunomide
- •cyclophosphamide, azathioprine or cyclosporine
- •sulphasalazine (SSZ) for more than 3 weeks
- •hydroxychloroquine for more than 6 weeks
- •oral Glucocorticoids (GC) for more than 4 weeks within 4 months before screening
- •oral GC at a daily dosage of more than 10 mg prednisone equivalent within 4 weeks before baseline
- •oral GC at a daily dosage equal to or less than 10 mg prednisone equivalent within 2 weeks before baseline
- •intra-articular GC within 4 weeks before BL
- •an investigational drug for the treatment/prevention of RA
- •History of chronic heart failure
- •History of severe infections or chronic infection
- •History of malignant neoplasm within 5 years
- •Contra indications for GC
- •Contra indications for TNF blocking agents
- •Contra indications for MTX or leflunomide
- •Psoriatic Arthritis
- •Underlying cardiac, pulmonary, metabolic, renal or gastrointestinal conditions, chronic or latent infectious diseases or immune deficiency which in the opinion of the investigator places the patient at an unacceptable risk for participation in the study
- •Pregnancy, breastfeeding or no use of a reliable method of contraception for woman of childbearing potential (as in daily clinical practice)
- •Alcohol or drug abuse
- •Active tuberculosis (TB)
- •Latent TB unless adequate prophylactic treatment is given according to local guidelines
- •No access to the Belgian Health Insurance system-
研究组 & 干预措施
standard COBRA-Slim induction
Leflunomide 10mg PO daily added to the COBRA-Slim scheme (Methotrexate 15 mg PO weekly, Step down scheme of GC: 30-20-12,5-10-7,5-5 mg prednisone PO daily, each for 7 days except for the lowest dose of 5 mg, this will be maintained until w28 and then tapered to 2.5 mg daily for two weeks before stopping completely.)
干预措施: Leflunomide 10 milligram (MG) (Drug)
COBRA-Slim Bio-induction
Etanercept 50mg subcutaneous (SC) weekly added for 24 weeks to COBRA-Slim scheme (Methotrexate 15 mg PO weekly, Step down scheme of GC: 30-20-12,5-10-7,5-5 mg prednisone PO daily, each for 7 days except for the lowest dose of 5 mg, this will be maintained until w28 and then tapered to 2.5 mg daily for two weeks before stopping completely.)
干预措施: Etanercept 50 MG/ML (Drug)
结局指标
主要结局
Area Under Curve (AUC) of Disease Activity Score Based on a 28 Jointcount and C-reactive Protein (DAS28CRP)
时间窗: baseline, w4, w8, w16, w24, w32, w40, w52, w64, w78, w92 and w104
Analysis was based on an intention to treat population, which focused on all patients randomized into the study, irrespective if they actually received the randomized treatment. Fifty-five patients were allocated to Standard COBRA-Slim and 55 to COBRA-Slim Bio-induction. This measure is an indication of the total disease-activity over time or long-term effectiveness, a higher area under the curve indicates a higher disease activity over time and so a lower effectiveness over the time frame of the trial. The scale range for the duration of the trial (104 weeks) is 0.0 to 977.6 * remission: value below 270.4 * low disease activity: from 270.4 till 332.8 (included) * moderate disease activity: above 332.8 till 530.4 * high disease activity: above 530.4
次要结局
- Proportion of Insufficient Responders Achieving Remission (DAS28CRP<2.6) 28 Weeks After Randomization (Short Term Efficacy) to Either COBRA-Slim Bio-Induction or Standard COBRA-Slim Induction(From randomization till 28 weeks after randomization.)
- Proportion of Patients in Remission Defined as DAS28CRP<2.6(at week 104)
- Proportion of Patients Achieving a EULAR Response(at week 104)
- Health Assessment Questionnaire (HAQ) Response(at week 104)
- Radiographic Progression(at week 104)
研究者
P. Verschueren
Prof. Dr.
Universitaire Ziekenhuizen KU Leuven