Treat-to-Target Strategy With Etanercept for Ankylosing Spondylitis: a Prospective, Randomized Multicentric Study on Disease Activity Guided Etanercept Tapering or Discontinuation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 311
- 主要终点
- Cumulative flare rates at week 48 with different tapering or discontinuation strategies
研究概览
简要总结
Evaluate the disease activity guided tapering and discontinuation strategies of etanercept (ETN) in patients with ankylosing spondylitis (AS) in 48 weeks.
详细描述
Ankylosing spondylitis (AS), a subset of axial spondyloarthritis (axSpA), is a chronic inflammatory disorder characterized by inflammatory back pain and predominant involvement of sacroiliac joints and spine, leading to bony fusion of vertebrae and eventually disability in some patients. Nonsteroidal anti-inflammatory drugs (NSAIDs) are recognized as a first-line therapy for AS, but the overall response rates to NSAIDs are considerably unsatisfactory. With the advent of biologics, the outcomes of AS patients have been greatly improved. Biologics including tumor necrosis factor α (TNFα) inhibitors (TNFi) have been included in many recommendations for the treatment of AS. Etanercept, a recombinant human TNFα receptor, is capable of binding to TNFα and blocking its biological activities. It is effective in relieving symptoms, improving physical function, and reducing disease activity in patients with AS, and generally no severe adverse effects have been reported. However, the high expense of biologics restricts their long-term use, which urges a viable strategy to reduce the dosage of biologics while maintaining an optimal therapeutic efficacy. To investigate the stepwise tapering and discontinuation of TNFi based on disease activity in patients with AS, a 48-week, prospective, randomized, multicentric study was conducted. An etanercept biosimilar, rhTNFR:Fc (recombinant TNF receptor: Fc fusion protein, Yisaipu), which is one of the most widely used biosimilars in China, was used in this study.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •aged between 18 years old and 65 years old with AS, according to 1984-revised New York classification criteria.
- •an active disease of ASDAS with C reactive protein (ASDAS-CRP) ≥2.
- •a disease duration of 6 months to 30 years.
- •no exposure to biologics in recent 6 months before recruitment. Concomitant medications with NSAIDs, conventional disease modifying anti-rheumatic drugs (cDMARDs), or prednisone or a prednisone equivalent (≤10mg/day), were allowed to continue if they were maintained at a stable dose for 4 weeks or more from baseline.
排除标准
- •late-stage patients with spinal fusion.
- •patients with severe cardiac, hepatic, renal, hematologic or endocrine diseases.
- •patients with a history of multiple sclerosis, current or past malignancy.
- •patients who were pregnant, or planning to become pregnant, or breastfeeding.
- •patients with active or recurrent infections, or those who required oral antibiotics 2 weeks or intravenous antibiotics 4 weeks before screening.
- •patients with current or past or potential tuberculosis.
研究组 & 干预措施
inactive - half dosage tapering
Active AS patients with AS disease activity score (ASDAS)≥2.1 were recruited from ten hospitals, initially managed with ETN 50mg weekly for 12 weeks, and then randomized into subgroups with different tapering or discontinuation strategies according to ASDAS at week 12. Patients in this arm were those who achieved inactive disease (ASDAS<1.3, group A) at week 12 and assigned to sequential tapering group (A1).
干预措施: tapering or discontinuation of etanercept (Drug)
inactive - discontinuation
Active AS patients with AS disease activity score (ASDAS)≥2.1 were recruited from ten hospitals, initially managed with ETN 50mg weekly for 12 weeks, and then randomized into subgroups with different tapering or discontinuation strategies according to ASDAS at week 12. Patients in this arm were those who achieved inactive disease (ASDAS<1.3, group A) at week 12 and then assigned to discontinuation group (A2).
干预措施: tapering or discontinuation of etanercept (Drug)
low disease activity - half dosage tapering
Active AS patients with AS disease activity score (ASDAS)≥2.1 were recruited from ten hospitals, initially managed with ETN 50mg weekly for 12 weeks, and then randomized into subgroups with different tapering or discontinuation strategies according to ASDAS at week 12. Patients in this arm were those who reached low disease activity (LDA) (1.3≤ASDAS<2.1, group B) and designated to sequential tapering group (B1).
干预措施: tapering or discontinuation of etanercept (Drug)
low disease activity - full dosage tapering
Active AS patients with AS disease activity score (ASDAS)≥2.1 were recruited from ten hospitals, initially managed with ETN 50mg weekly for 12 weeks, and then randomized into subgroups with different tapering or discontinuation strategies according to ASDAS at week 12. Patients in this arm were those who reached low disease activity (LDA) (1.3≤ASDAS<2.1, group B) and designated to delayed tapering group (B2) with extra 12 weeks of full dose ETN.
干预措施: tapering or discontinuation of etanercept (Drug)
low disease activity - discontinuation
Active AS patients with AS disease activity score (ASDAS)≥2.1 were recruited from ten hospitals, initially managed with ETN 50mg weekly for 12 weeks, and then randomized into subgroups with different tapering or discontinuation strategies according to ASDAS at week 12. Patients in this arm were those who reached low disease activity (LDA) (1.3≤ASDAS<2.1, group B) and designated to discontinuation group (B3).
干预措施: tapering or discontinuation of etanercept (Drug)
结局指标
主要结局
Cumulative flare rates at week 48 with different tapering or discontinuation strategies
时间窗: 48 weeks
Cumulative flare rates at week 48 with different tapering or discontinuation strategies
次要结局
未报告次要终点