Randomized Controlled Clinical Trial Evaluating Methotrexate or Leflunomide + Targeted Therapy Versus Methotrexate or Leflunomide + Sulfasalazine + Hydroxychloroquine in Patients with Rheumatoid Arthritis and Insufficient Response to Methotrexate or Leflunomide
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 286
- 试验地点
- 1
- 主要终点
- Numbers of participant with low disease activity (DAS28-CRP<3.2) and a daily dose ≤ 7.5 mg/day of equivalent prednisone
研究概览
简要总结
Approximately, 40 to 50% of patients with rheumatoid arthritis (RA), the most frequent inflammatory arthritide, are non responders to the consensual 1st line of treatment : methotrexate. In these patients, it is well demonstrated that the addition of other immunomodulatory drug(s) often results in a significant improvement. However, the best option regarding the drug(s) to add remains unclear. Rheumatologists are currently used to adding a targeted therapy, such as anti-TNFα, and more recently abatacept or tocilizumab. Triple therapy using 3 conventional disease-modifying drugs (DMARDs), methotrexate or leflunomide+salazopyrine+hydroxychloroquine could be an alternative option to targeted therapies, all the more as they have a more favorable safety profile and a much lower cost. Uncertainty remains regarding the superiority of targeted therapies on triple therapy in methotrexate or leflunomide insufficient responders (IR). Investigators decided to address this issue by performing a randomized controlled pragmatic trial.
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
- •Patient with rheumatoid arthritis according to EULAR/ACR 2010 criteria
- •DAS28-CRP>3.2
- •Insufficient response to methotrexate at a weekly dose≥15mg after at least 3 months or to leflunomide at a dose of 10 (in case 20 mg are not well tolerated) to 20 mg per day after 3 months of treatment
- •RA radiographic erosions and/or serum rheumatoid factor associated to anti-Cyclic Citrullinated Peptide (Anti-CCP)
- •Age greater or equal to 18 years
- •Written informed consent, dated and signed before initiating any trial-related procedure
- •Affiliation to a social insurance system
- •Women of child bearing potential, negative β-HCG assay (Human chorionic gonadotropin)
- •Effective method of birth control during the study and continuing after the discontinuation of the investigational drug or study. The duration will depend on the drug used (referred to the summary product characteristic).
排除标准
- •Previous treatment with or contraindication to targeted therapies (biologic or JAK/STAT inhibitor)
- •Previous treatment with triple therapy
- •Other inflammatory arthritis except RA associated with Sjögren's syndrome
- •Contraindication to all biologics/ JAK/STAT inhibitors or to methotrexate, leflunomide, sulfasalazine and hydroxychloroquine
- •Corticosteroids at a dose >15 mg/d of equivalent prednisone for at least 4 weeks before the inclusion
- •Absence of tuberculosis screening
- •Patient who cannot be followed during 12 months
- •Pregnancy, breastfeeding, desire of pregnancy in the 12 months
- •Drug addiction, addiction to alcohol
- •Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment
- •Women of child bearing potential, unless they are using an effective method of birth control
- •Patient under law protection
- •Prisoners
研究组 & 干预措施
methotrexate + targeted therapy group
Methotrexate or leflunomide +
targeted therapy chosen by investigator
干预措施: Methotrexate + targeted therapy administration (Drug)
Triple therapy
Triple therapy using 3 conventional disease modifying drugs (DMARDs)
干预措施: methotrexate or leflunomide + sulfasalazine + hydroxychloroquine administration (Drug)
结局指标
主要结局
Numbers of participant with low disease activity (DAS28-CRP<3.2) and a daily dose ≤ 7.5 mg/day of equivalent prednisone
时间窗: At 12 months
次要结局
- Clinical disease activity index (CDAI).(At inclusion, 3, 6, 9 and 12 months)
- QUALISEX score at inclusion, 6 months and at 12 months.(at inclusion, 6 months and at 12 months.)
- Serious adverse events rate(At 3, 6, 9 and at 12 months)
- Blood concentrations of hydroxychloroquine, leflunomide, sulfasalazine and methotrexate in the triple therapy group and methotrexate, leflunomide, biologic / JAK/STAT inhibitor and anti-drug antibody in the other group.(at 6, and 12 months)
- DAS 28 CRP score.(at inclusion, 3, 6, 9 and 12 months.)
- 2010 ACR (American College of Rheumatology)/EULAR classification Criteria for RA, ACR 20, 50, 70 and boolean remission.(at 3, 6, 9 and 12 months.)
- Change in comedications (dose)(at 3, 6, 9 and 12 months)
- Change in comedications (route of administration)(at 3, 6, 9 and 12 months)
- Modified Sharp Van der Heijde score.(at inclusion and at 12 months)
- Change in comedications (drug)(at 3, 6, 9 and 12 months)
- Medico-economic costs.(at inclusion, 3, 6, 9 and at 12 months.)
- Treatment compliance(at 3, 6, 9 and 12 months)