Therapeutic Drug Monitoring-baSed adalimuMab De-escalatiOn in nOn-infecTious cHronic Uveitis: an Open-label, Non-inferiority, Randomised Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 320
- 试验地点
- 21
- 主要终点
- Maintenance of a complete ophthalmological response at 48 weeks
研究概览
简要总结
Uveitis and its complications are thought to account for 10 to 15% of preventable blindness in Western countries. The diagnosis of chronic non-infectious uveitis (CNUI) can be made after exclusion of pseudo uveitis or infectious uveitis, in the case of any persistent uveitis or uveitis with frequent relapses occurring less than 3 months after cessation of treatment. Adalimumab (ADA), an anti-TNFα monoclonal antibody, has marketing authorization and is widely used in the treatment of UCNI as a relay to corticosteroids. The use of ADA has been optimized, in particular through Therapeutic Drug Monitoring (TDM), based on the determination of serum ADA levels and anti-ADA antibodies. Recently, an article showed that a strategy of spacing ADA administrations in RA patients with concentrations >8 μg/mL was not inferior to standard.
详细描述
There is currently no formal recommendation for spacing ADA administration in patients with chronic noninfectious uveitis, but promising data from a recent retrospective study conducted by the Croix-Rousse team, led to the proposal of a decision support algorithm. Following the example of what has been shown in rheumatoid arthritis, the investigators propose to compare a strategy of spacing ADA administrations in patients with a satisfactory clinical response associated with high serum ADA concentrations.
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
- Single (Investigator)
盲法说明
The primary endpoint will be assessed by blinding the allocated treatment group to investigator.
Thus, ophthalmological response will be assessed in a standardised manner by an ophthalmologist, blinded to the treatment strategy. The occurrence of infections will also be assessed in a manner blinded to the by an independent adjudication committee.
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
- •Informed and having signed the study consent form
- •Age ≥ 18 years
- •NICU according to the Standardization of Uveitis Nomenclature (SUN) criteria
- •Complete ophthalmological response for ≥ 48 weeks (96 weeks for uveitis related to Behçet's disease), all treatments combined
- •On ADA 40mg / 14 days for ≥ 24 weeks (i.e. achievement of the steady state for ADA concentrations)
- •Not having received systemic corticosteroid therapy for ≥ 12 weeks
排除标准
- •Inability or refusal to understand and/or sign the informed consent form to participate in the study.
- •Inability and/or refusal to carry out the follow-up examinations required for the study.
- •Modification of any background immunomodulatory treatment (e.g. methotrexate, hydroxychloroquine, mycophenolate, etc.) associated with ADA, during the 12 weeks prior to inclusion.
- •Uveitis suspected or proven to be of infectious origin
- •Planned surgery (or other foreseeable medical event) requiring discontinuation of ADA for the duration of the study.
研究组 & 干预措施
Control arm : conventional strategy
At W0, ADA administration will be continued every 14 days. At W24, the control arm will continue to receive ADA every 14 days regardless of serum ADA concentration.
干预措施: Blood sample (Diagnostic Test)
Arm 2: Interventional arm : adalimumab dose spacing strategy
At W0, if the serum ADA concentration is ≥ 8 μg/mL, ADA administration will be spaced every 21 days. At W24, if the ADA concentration is < 3.3 μg/mL (having a serum ADA concentration above this threshold was associated with a complete therapeutic response according to one study), administrations will be repeated every 14 days. If the ADA concentration is ≥ 3.3 and < 8μg/mL, administrations will be left every 21 days. If ADA concentration is still ≥8μg/mL, ADA administrations will be spaced every 28 days.
干预措施: Blood sample (Diagnostic Test)
Control arm : conventional strategy
At W0, ADA administration will be continued every 14 days. At W24, the control arm will continue to receive ADA every 14 days regardless of serum ADA concentration.
干预措施: Adalimumab Injection (Drug)
Arm 2: Interventional arm : adalimumab dose spacing strategy
At W0, if the serum ADA concentration is ≥ 8 μg/mL, ADA administration will be spaced every 21 days. At W24, if the ADA concentration is < 3.3 μg/mL (having a serum ADA concentration above this threshold was associated with a complete therapeutic response according to one study), administrations will be repeated every 14 days. If the ADA concentration is ≥ 3.3 and < 8μg/mL, administrations will be left every 21 days. If ADA concentration is still ≥8μg/mL, ADA administrations will be spaced every 28 days.
干预措施: Adalimumab Injection (Drug)
结局指标
主要结局
Maintenance of a complete ophthalmological response at 48 weeks
时间窗: Week 48
Number of patient with complete ophthalmological response. Ophtalmological response is defined as number of patient with, in both eyes, absence of inflammatory lesions (0 = absence) AND a cellular grade of the anterior chamber and vitreous ≤ 0.5+.
Infection
时间窗: Week 48
Number of infection during follow-up for up to 48 weeks. Any suspected infectious event will have to be validated by a healthcare professional based on the presence of suggestive clinical signs (purulent sputum, fever ≥38°C, inflammatory syndrome, positive microbiological examination, etc.) via dedicated forms and validated by an adjudication committee.
次要结局
- Maintenance of a complete ophthalmological response at 12 weeks(Weeks 12)
- Maintenance of a complete ophthalmological response at 24 weeks(Weeks 24)
- Maintenance of a complete ophthalmological response at 36 weeks(Weeks 36)
- Infection(Week 36)
- Anti-ADA antibody positivity(Weeks 48)
- Anti-ADA antibody positivity(Weeks 24)
- Anti-ADA antibody positivity(Weeks 36)
- Infection(Week 12)
- Infection(Week 24)
- Anti-ADA antibody positivity(Weeks 12)