Treat-to-target Strategy in Ankylosing Spondylitis Using Etanercept and Conventional Synthetic DMARDs, a Prospective Randomized Controlled Study
试验速览
- 阶段
- 4 期
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Assessment in Ankylosing Spondylitis 20 (ASAS-20) Response
研究概览
简要总结
This study evaluates clinical responses and cost-effectiveness of using etanercept (ETN) and conventional synthetic Disease modifying anti-rheumatic drugs (csDMARDs) with treat-to-target strategy in ankylosing spondylitis patients. Half of participants will be used treat-to-target strategy with ETN and csDMARDs, while the others will be used conventional therapy scheme with ETN only.
详细描述
The tumor necrosis factor inhibitors(TNFi) like etanercept(ETN) has been always recommended as the primary treatment option for active AS. But when sustained applied in daily clinical practices, it is unaffordable for patients in developing countries in most cases due to the high expense of TNFi. On this ground, this study proposes a new scheme dividing AS treatment into relatively active phase and relatively stable phase, and sequentially introducing TNFi and conventional synthetic Disease modifying anti-rheumatic drugs (csDMARDs) in each phase respectively. Taking full advantages of the rapid and precise efficacy of TNFi when short-term application in active AS and then csDMARDs combination was prescribed to maintain the remission cause by TNFi. Drug regimes are adjusted according to the different responses of individual patient based on treat-to-target strategy. TNFi is reintroduced if there is a reactive tendency and then switching to csDMARDs again when patients are in remission. Thus, the continuous low activity or remission of AS may be promising through this treating management and the treatment cost will reduce for csDMARDs partially replace TNFi in the management of relatively stable phase.
This study is designed as a prospective randomized, positive controlled, 48-week clinical trial, involving 100 patients with active ankylosing spondylitis. All enrolled patients will randomly assign to 2 groups for the comparison of the clinical responses and cost-effectiveness of our treatment scheme with that of the conventional therapy scheme of TNFi (etanercept). Multiple clinical indexes will be measured to evaluate the therapeutic effect, including Patient's Global Assessment, BASDAI and ASDAS-CRP for disease activity, BASFI for functional state, EQ-5D and SF-36 for quality-of-life assessment, SPARCC and SPARCC Sacroiliac Joint Structural Score (SSS) for sacroiliac joint invasion. We expect to assess the feasibility of our new treatment scheme in AS disease controlling and cost-effectiveness improving through this one-year follow-up study.
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Capability to understand and voluntarily give written informed consent that is signed and dated, before any specific procedure of the protocol is performed.
- •Patients 18 to 45 years of age.
- •Proven AS according to the modified New York criteria.
- •Acute phase of disease with ASDAS score ≥1.
- •Ability to reconstitute the drug and self-inject it or have a person who can do so.
- •Ability to store injectable test article at 2º to 8º C.
排除标准
- •Patients with a history of active tuberculosis, hepatitis, gastrointestinal hemorrhage, tumors, infectious diseases or combined with other rheumaimmune systemic diseases or osteoarthritis diseases.
- •Pregnancy/lactation.
- •Receipt of any live (attenuated) vaccines within 4 weeks before the screening visit.
- •Significant concurrent medical diseases including uncompensated congestive heart failure (NYHA III-IV), myocardial infarction within 12 months, stable or unstable angina pectoris, uncontrolled hypertension, severe pulmonary disease, history of human immunodeficiency virus (HIV) infection.
- •Participation in trials of other investigational medications within 30 days of entering the study.
- •Clinical examination showing significant abnormalities of clinical relevance.
研究组 & 干预措施
Group 1. Experimental
Etanercept 50mg per week plus conventional synthetic DMARDs(csDMARDs, methotrexate 10mg per week, sulfasalazine 2.25g per day, hydroxychloroquine 0.2g per day) for 4 weeks when in high disease activity; etanercept 50mg per week plus csDMARDs for 2 weeks and continue with csDMARDs only for 2 weeks when in low disease activity; csDMARDs only for 4 weeks when in disease remission status.
干预措施: Methotrexate (Drug)
Group 1. Experimental
Etanercept 50mg per week plus conventional synthetic DMARDs(csDMARDs, methotrexate 10mg per week, sulfasalazine 2.25g per day, hydroxychloroquine 0.2g per day) for 4 weeks when in high disease activity; etanercept 50mg per week plus csDMARDs for 2 weeks and continue with csDMARDs only for 2 weeks when in low disease activity; csDMARDs only for 4 weeks when in disease remission status.
干预措施: Sulfasalazine (Drug)
Group 1. Experimental
Etanercept 50mg per week plus conventional synthetic DMARDs(csDMARDs, methotrexate 10mg per week, sulfasalazine 2.25g per day, hydroxychloroquine 0.2g per day) for 4 weeks when in high disease activity; etanercept 50mg per week plus csDMARDs for 2 weeks and continue with csDMARDs only for 2 weeks when in low disease activity; csDMARDs only for 4 weeks when in disease remission status.
干预措施: Hydroxychloroquine (Drug)
Group 1. Experimental
Etanercept 50mg per week plus conventional synthetic DMARDs(csDMARDs, methotrexate 10mg per week, sulfasalazine 2.25g per day, hydroxychloroquine 0.2g per day) for 4 weeks when in high disease activity; etanercept 50mg per week plus csDMARDs for 2 weeks and continue with csDMARDs only for 2 weeks when in low disease activity; csDMARDs only for 4 weeks when in disease remission status.
干预措施: Etanercept (50mg per week, for 4 weeks) (Drug)
Group 1. Experimental
Etanercept 50mg per week plus conventional synthetic DMARDs(csDMARDs, methotrexate 10mg per week, sulfasalazine 2.25g per day, hydroxychloroquine 0.2g per day) for 4 weeks when in high disease activity; etanercept 50mg per week plus csDMARDs for 2 weeks and continue with csDMARDs only for 2 weeks when in low disease activity; csDMARDs only for 4 weeks when in disease remission status.
干预措施: Etanercept (50mg per week, for 2 weeks) (Drug)
Group 2. Positive Control
Etanercept 50mg per week for first 12 weeks; etanercept 50mg per ten days for second 12 weeks; etanercept 25mg per week for next 12 weeks; etanercept 25mg per two week for next 12 weeks.
干预措施: Etanercept (50mg per week) (Drug)
结局指标
主要结局
Percentage of Participants With Assessment in Ankylosing Spondylitis 20 (ASAS-20) Response
时间窗: Week 12, 24, 36, 48
ASAS measures symptomatic improvement in AS participants. ASAS = 4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 20= at least \>= 20 percent improvement from baseline and an absolute change \>=1 unit on a 0-10 numeric scale (0=no disease activity; 10=high disease activity) in at least 3 of the domains (on a 0-10 numerical scale): Global assessment of disease activity by participant, participant's global pain intensity, function measured by BASFI and inflammation measured by the average of the last two Likert-scales in BASDAI concerning morning stiffness intensity and duration and no worsening in the remaining domain.
Percentage of Participants With Assessment in Ankylosing Spondylitis 40 (ASAS-40) Response
时间窗: Week 12, 24, 36, 48
ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) participants. ASAS =4 domains: participant global assessment of disease activity, pain, function, inflammation. ASAS 40= at least (\>=) 40 percent improvement from baseline and an absolute change \>=2 unit on a 0-10 numeric scale (0=no disease activity; 10=high disease activity) in at least 3 of the domains (on a 0-10 numerical scale): Global assessment of disease activity by participant, participant's global pain intensity, function measured by BASFI and inflammation measured by the average of the last two Likert-scales in BASDAI concerning morning stiffness intensity and duration and no worsening in the remaining domain.
次要结局
- Mean Change From Baseline in Erythrocyte Sedimentation Rate (ESR)(Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
- Mean Change From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score(Baseline, Week 12, 24, 36, 48)
- Mean Change From Baseline in Ankylosing Spondylitis Disease Activity (ASDAS) Score(Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
- Mean Change From Baseline in SpondyloArthritis Research Consortium of Canada (SPARCC) Score for the Sacroiliac Joint(Baseline, Week 4, 12, 24, 48)
- Percentage of Participants with Serious Adverse Events (SAEs) or Adverse Events (AEs) by Co-morbidity From Baseline(Baseline, Week 12, 24, 36, 48)
- Mean Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score(Baseline, Week 12, 24, 36, 48)
- Mean Change From Baseline in C-Reactive Protein (CRP)(Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
- Mean Change From Baseline in Euro Quality of Life-5 Dimensions (EQ-5D) Score(Baseline, Week 12, 24, 36, 48)
- Mean Change From Baseline in Short Form-36 Health Survey (SF-36) Score(Baseline, Week 12, 24, 36, 48)