Rotation or Change of Biotherapy After TNF Blocker Treatment Failure for Axial Spondyloarthritis
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 300
- 试验地点
- 35
- 主要终点
- Proportion of axSpA patients with a clinical response Assessments in Ankylosing Spondylitis International Society 40 (ASAS 40) at week 24
研究概览
简要总结
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease characterized by inflammatory arthritis and enthesitis involving the spine. AxSpA prevalence is around 0.17% of the French population. Tumor necrosis factor (TNF) was the first target defined in axSpA. Since one third of axSpA patients failed to the first TNF blocker, many axSpA patients received a second biological Disease-Modifying AntiRheumatic Drugs (bDMARDs). Until few months, the only choice was to use a second TNF blocker.Since 2003, pharmaceutical companies investigated efficacy of TNF blockers already used in rheumatoid arthritis. Etanercept is a fusion protein with TNF receptor type II p75 and IgG1 Fc fragment, whereas adalimumab, infliximab, and golimumab are monoclonal antibodies. Certolizumab is a fusion between a fab fragment targeting TNF and a Peg fraction. All demonstrated efficacy versus placebo in a randomized double blinded study
In case of failure to the first TNF blockers, rheumatologists will follow the "Treat-to-Target" principle. This approach already demonstrated its benefit in rheumatoid arthritis or in psoriatic arthritis. This concept was also suggested for axSpA with low levels of evidence and recommendation. So rheumatologist will provide the best treatment in case of failure to the first TNF blockers, which is a daily clinical situation. Since few months, rheumatologists have the choice between targeting IL-23/17 axis compared to a second TNF blocker.
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
- •Active axSPA with BASDAI>4 or ASDAS>3.5, who need change in TNF blocker treatment
- •Aged over 18 years
- •Inadequate response after at least 3 months to the 1st TNF blocker
- •If non biologic DMARD treatment : stable dose for at least on month before inclusion
- •If oral corticosteroids treatment : stable dose for at least on month before inclusion
- •If NSAIDs treatment : stable dose for at least on month before inclusion
- •Ability to complete questionnaires
- •Social security affiliation
- •Informed written consent given
排除标准
- •Any contra-indication to TNF blocker and/or secukinumab
- •Inflammatory bowel diseases
- •Existing pregnancy, lactation, or intended pregnancy within the next 15 months Active tuberculosis or other severe infections such as sepsis or opportunistic infections
- •Active infections, including chronic or localised infections.
- •Moderate to severe heart failure (NYHA classes III/IV)
- •Impossibility to give informed consent
- •Impossibility to be followed for 12 months
研究组 & 干预措施
targeting IL-23/17 axis
The experimental group (targeting IL-23/17 axis) receiving secukinumab in compliance with the marketing authorization regimen: 150 mg per week for 5 weeks, and then every month by subcutaneous injection.
Blood specimen at each visits
干预措施: Secukinumab (Drug)
targeting IL-23/17 axis
The experimental group (targeting IL-23/17 axis) receiving secukinumab in compliance with the marketing authorization regimen: 150 mg per week for 5 weeks, and then every month by subcutaneous injection.
Blood specimen at each visits
干预措施: blood specimen (Biological)
TNF blocker
• The control group receiving a second TNF blocker in compliance with the marketing authorization regimen:
The TNF blocker (originator or biosimilar) will be different to the TNF used before the inclusion and will be chose by the investigator:
- infliximab: 5mg/kg per IV infusion at weeks 0, 2, 6, and then every 6 weeks,
- etanercept: 50mg per week in subcutaneous injection,
- adalimumab: 40mg every other week in subcutaneous injection,
- certolizumab: 400mg every other week 3 times, and then 200mg every other week or 400mg per month in subcutaneous injections,
- golimumab: 50mg every month in subcutaneous injection, in case of overweight (>100kg) an inadequate response, 100mg every month is allow.
Blood specimen at each visits
干预措施: TNF blocker (Drug)
TNF blocker
• The control group receiving a second TNF blocker in compliance with the marketing authorization regimen:
The TNF blocker (originator or biosimilar) will be different to the TNF used before the inclusion and will be chose by the investigator:
- infliximab: 5mg/kg per IV infusion at weeks 0, 2, 6, and then every 6 weeks,
- etanercept: 50mg per week in subcutaneous injection,
- adalimumab: 40mg every other week in subcutaneous injection,
- certolizumab: 400mg every other week 3 times, and then 200mg every other week or 400mg per month in subcutaneous injections,
- golimumab: 50mg every month in subcutaneous injection, in case of overweight (>100kg) an inadequate response, 100mg every month is allow.
Blood specimen at each visits
干预措施: blood specimen (Biological)
结局指标
主要结局
Proportion of axSpA patients with a clinical response Assessments in Ankylosing Spondylitis International Society 40 (ASAS 40) at week 24
时间窗: 24 weks
ASAS 40 is defined as an improvement of at least 40% and absolute improvement of at least 2 units on a numerical rating scale of 10 in at least 3 of the following domains compared to values at inclusion: * Patient global assessment : numerical rating scale with extremes labelled "none" and "severe." * Pain assessment : average of total and nocturnal pain scores, both measured on a numerical rating scale with extremes labelled "no pain" and "most severe pain." * Function : BASFI average of 10 questions measured by numerical rating scale with extremes labelled "easy" and "impossible." * Morning stiffness, represented by the average of the last 2 questions on the 6-question BASDAI measured by numerical rating scale: one with extremes labelled "none" and "very severe"; the other marking duration of morning stiffness between "0" and "2 or more hours." Additionally, no worsening at all in remaining domain
次要结局
- Proportion of axSpA patients with a ASDAS major improvement at week 52(52 weeks)
- Proportion of axSpA patients with a clinical response ASAS 40 at week 12(12 weeks)
- Proportion of axSpA patients with a clinical response ASAS 40 at week 52(52 weeks)
- Proportion of axSpA patients with a clinical response ASAS 20 at week 12(52 weeks)
- Proportion of axSpA patients with a clinical response ASAS 20 at week 24(24 weeks)
- Proportion of axSpA patients with a ASDAS major improvement at week 24(24 weeks)
- Proportion of axSpA patients with a clinical response ASAS20 at week 52(52 weeks)
- Proportion of axSpA patients with a partial remission rate at week 24(24 weeks)
- Proportion of axSpA patients with a partial remission rate at week 12(12 weeks)
- Proportion of axSpA patients with a partial remission rate at week 52(52 weeks)
- Proportion of axSpA patients with a ASDAS major improvement at week 12(12 weeks)
- Proportion of axSpA patients with biological Disease-Modifying AntiRheumatic Drugs (bDMARDs) treatment at week 12(12 weeks)
- Proportion of axSpA patients with biological Disease-Modifying AntiRheumatic Drugs (bDMARDs) treatment at week 24(24 weeks)
- Proportion of axSpA patients with bDMARDs treatment at week 52(52 weeks)
- Number of adverse events(52 weeks)
- Correlation between concentration of antibodies to bDMARS blockers and clinical response according to treatment(From baseline to 52 weeks)
- Correlation between concentration of anti-drug antibodies and clinical response according to treatment(From baseline to 52 weeks)