A Prospective, Randomized Biologic Tapering Study of TNF Inhibitors in Axial Spondyloarthritis
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Proportion of patients able to maintain inactive disease or low disease activity, defined as Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3 to 2.1 or Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) of <4 on tapered-dose TNFi
研究概览
简要总结
Current evidence on tapering of tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) is still hampered by heterogeneity in tapering regimens, selection and performance biases, and lack of data on optimized treatment dosing strategies especially in real-world clinical settings. This study aims to contribute to the ongoing investigation of disease-activity-guided tapering of TNFi in axSpA in the form of a prospective, randomized controlled trial.
详细描述
This is a 48-week randomized, controlled, open-label, non-inferiority trial of patients with radiographic or non-radiographic axial spondyloarthritis. The study will include 156 patients with inactive disease or low disease activity (LDA) for at least 6 months on a TNFi at the time of randomization.
Participants will be randomized using a 1:1 ratio to either the tapered-dose arm or the standard-dose arm of TNFi. Progressive tapering of TNFi according to a predefined protocol will be allowed as long as the patient is able to maintain inactive disease or LDA during the study period. We hypothesize that, in patients with 6 months or more of inactive or low-activity axial spondyloarthritis, tapered-dose TNFi are non-inferior to standard-dose TNFi in sustaining the disease state for at least 1 year.
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
- •Adult axSpA patients satisfying the 2009 Assessment of SpondyloArthritis International Society (ASAS) Classification Criteria
- •Currently enrolled in the SPARCC Program with successful completion of standard data collection protocol in the Spondylitis Clinic of UHN-Toronto Western Hospital
- •Have sustained inactive disease or LDA with an ASDAS of <2.1 or BASDAI <4 for at least 6 months
- •On a stable dose of a TNFi (infliximab, etanercept, adalimumab, certolizumab pegol, or golimumab)
- •Must not be pregnant
排除标准
- •Adults axSpA patients with active extra-articular manifestations such as inflammatory bowel disease, psoriasis, and/or uveitis
- •Have comorbidities that may preclude clinical assessment (i.e. fibromyalgia or other chronic pain syndromes; chronic inflammatory diseases other than axSpA)
- •Have diagnosed psychiatric or personality disorders
- •Not enrolled in the Spondyloarthritis Research Consortium of Canada (SPARCC) Program
研究组 & 干预措施
Tapered doses of TNFi
Tapering of TNFi through standardized increases in the dosing interval between drug administration. The tapering dose intervals for each TNFi are designed to decrease the dose from baseline by 75% for 12 weeks, 50% for 24 weeks, and 25% for 12 weeks
干预措施: Tapered doses of TNFi (Drug)
Standard dose of TNFi
Stable doses of TNFi according to the approved summary of product characteristics for biologic agents used in axial spondyloarthritis
干预措施: Standard dose of TNFi (Drug)
结局指标
主要结局
Proportion of patients able to maintain inactive disease or low disease activity, defined as Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.3 to 2.1 or Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) of <4 on tapered-dose TNFi
时间窗: Weeks 12, 24, 36, and 48
The ASDAS and BASDAI are measures of axial spondyloarthritis disease activity for the past week. The ASDAS has 5 components scored from 0 to 10 (none to very severe). The following formula is used to compute for the ASDAS: (0.121 × back pain score) +(0.058 × score for duration of morning stiffness) + (0.11 × patient global assessment score) + (0.073 × peripheral pain/swelling score) + (0.579 × log(CRP+1)). The scores range from 0 (no disease activity) to infinity (being determined by the level of CRP). The disease is considered inactive if the final score is \<1.3, and low if \<2.1. The BASDAI consists of six items, with each item being scored from 0 ("none") to 10 ("very severe"). The final BASDAI scores ranges from 0 to 10, with lower scores indicating lower disease activity. A BASDAI of \<4 indicates inactive or low disease. As opposed to ASDAS, BASDAI does not include CRP in its formula. Either ASDAS or BASDAI is acceptable in clinical practice.
次要结局
- Proportion of patients with impaired work productivity and activity measured using the Work Productivity and Activity Impairment Questionnaire for Ankylosing Spondylitis (WPAI:SpA) questionnaire(Up to Week 48)
- Proportion of patients with radiographic progression, defined as an increase in the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) by 2 units(Baseline and Week 48)
- Mean quality of life in the tapered-dose arm vs. the standard-dose arm measured using the Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire(Up to Week 48)
- Factors predicting flare(Up to Week 48)
- Proportion of patients experiencing a disease flare by ASDAS or BASDAI(Up to Week 48)
- Proportion of patients with functional limitation measured using the Bath Ankylosing Spondylitis Functional Index (BASFI)(Up to Week 48)
- Proportion of patients needing concomitant medication(Up to Week 48)
- Proportion of patients with any related severe adverse event(Up to Week 48)
研究者
Robert Inman
Principal Investigator
University Health Network, Toronto