Tight Control Dose Reductions of Biologics in Psoriasis Patients With Low Disease Activity: A Randomized Pragmatic Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 6
- 主要终点
- Disease-activity
研究概览
简要总结
Rationale/hypothesis: Moderate-to-severe psoriasis can be treated with biologics.
Objective To investigate whether the dose of biologics can be reduced in patients with psoriasis with stable disease.
Study design: A pragmatic, multicentre, randomized, controlled, non-inferiority study with cost-effectiveness analysis.
Study population: Patients with disease remission using normal dose of biologics.
Intervention: 120 patients will be randomized into two groups: (1) dose reduction and (2) normal dose.
Main study parameters/endpoints: The primary outcome is clinical effectiveness. Secondary outcomes are: health-related quality of life (HRQoL), number and time to disease flares, costs, health status, anti-drug antibody formation and serious adverse events
详细描述
Rationale/hypothesis: Moderate-to-severe psoriasis can be treated with biologics. These drugs have significantly improved the quality of life of psoriasis patients, but are very expensive drugs that should be used as efficiently as possible. In addition, the long-term safety profile can probably be improved if patients receive the lowest effective dose.
Objective To investigate whether the dose of biologics can be reduced in patients with psoriasis with stable disease: Is dose reduction non-inferior to the current practice regarding clinical effectiveness? Secondary aims are: to investigate what influence dose tapering has on quality of life, whether there are predictors for successful dose reduction, and to determine the cost-effectiveness of dose reduction.
Study design: A pragmatic, multicentre, randomized, controlled, non-inferiority study with cost-effectiveness analysis.
Study population: Patients who used a biologic for at least 6 months (etanercept, adalimumab, ustekinumab) can be included if they have long-term stable low disease activity. Low disease activity is defined as a PASI score (Psoriasis Area and Activity Score) <5 and a health-related quality of life score ≤5 (Dermatology Quality of life index: DLQI).
Intervention: 120 patients will be randomized into two groups: (1) dose reduction guided by PASI and DLQI (n=60, intervention) and (2) maintenance of normal dosage (n=60, usual care).
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
- •Sustained low disease activity as described above on the dose as advised by the label.
- •Established diagnosis of plaque psoriasis.
- •Receiving treatment with adalimumab, etanercept, or ustekinumab for at least 6 months.*
- •Age ≥18 years.
- •Ability to understand informed consent, read and answer questionnaires.
排除标准
- •Psoriasis itself is not the main reason for biologic prescription (e.g. when a patient has RA and psoriasis, and RA is the main reason for the biologic).
- •Concomitant use of immunosuppressants other than methotrexate or acitretin for psoriasis.
- •Severe comorbidities with short life-expectancy (e.g. metastasized tumour).
- •Presumed inability to follow the study protocol.
研究组 & 干预措施
Dose decrease
Patients receive daily practice care, but doses of etanercept, adalimumab or ustekinumab will be lowered: intervals of drug-administration will be prolonged stepwise with tight control of disease activity and DLQI. First, the dose will be decreased to 66-70% of the normal dose (by interval prolongation with a factor 1.5). If patients remain in a state of low disease activity, the dose will be further reduced to 50% (by doubling the original interval). Each step will be analyzed after three months, or when the patient visits earlier due to complaints.
干预措施: Dose decrease (Other)
Usual care
Patients will continue treatment with the normal dose and treatment regimens will be based on usual daily practice care. Treatment decisions are made at the discretion of the treating physician.
干预措施: Usual care (Other)
结局指标
主要结局
Disease-activity
时间窗: 1 year
Disease-activity measured by Psoriasis Area and Severity Index (PASI), effectiveness measure used in most psoriasis trials.
次要结局
- Disease-activity measured with HsCRP(1 year)
- Costs related to medical consumption(1 year)
- Number of patients with 1 or more persistent flares(1 year)
- Health-related quality of life (HRQoL-DLQI)(1 year)
- Predictors for succesful dose decrease (treatment and patient characteristics)(1 year)
- Number of serious adverse events per patient(1 year)
- Drug trough levels of etanercept, adalimumab or ustekinumab(1 year)
- Costs related to productivity(1 year)
- Anti-drug antibody levels against etanercept, adalimumab or ustekinumab(1 year)
- Health status (SF36)(1 year)