Dose Reduction of the New Generation Biologicals (IL17 and IL23 Inhibitors) in Psoriasis: A Pragmatic, Multicentre, Randomized, Controlled, Non-inferiority Study - BeNeBio Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 244
- 试验地点
- 19
- 主要终点
- Non-inferiority of the incidence proportion of persistent flares (Psoriasis Area and Severity Index (PASI) >5 for ≥ 3 months).
研究概览
简要总结
The main objective of this study is to investigate whether controlled dose reduction of IL17 or IL23 inhibiting biologics is not inferior compared to usual care in psoriasis patients. Therefore, a pragmatic, multicentre, randomized, controlled, non-inferiority study will be carried out.
详细描述
Rationale: Biologics are very effective treatments for psoriasis. Research indicated that the dose of TNFα-blocking biologics can be reduced in a proportion of patients. Safety profiles can improve and costs can be reduced if the reduction of the dose is successful. Recently, the newest generation of biologics entered the market: interleukin (IL) 17 and IL23 inhibitors. It is not yet known whether dose reduction of these agents is possible, and to what extent they can be reduced. The timely investigation of the possibilities for dose reduction of new biologics is therefore important.
Objectives: The primary goal is to investigate whether controlled dose reduction of IL17 or IL23 inhibiting biologics is not inferior compared to usual care. This is measured by comparing the proportion of long-term disease flares between the two groups (dose reduction group versus usual care group). Secondary goals are: determining the proportion of patients with successful dose reduction, clinical effectiveness measured with the Psoriasis Area and Severity score (PASI) score, Dermatology Life Quality Index (DLQI) scores, predictors for successful dose reduction, safety, and cost-effectiveness of dose reduction. Pharmacokinetic (PK) analysis will be performed for modeling.
Study design: a multicenter, practice-oriented, pragmatic, randomized, controlled, non-inferiority study.
Study population: Patients treated with the newest generation of biologics (IL17 or IL23 inhibitors), with long-term stable low disease activity at a normal dose. A total of 244 patients will be randomized (2:1) to dose reduction or continuation of usual care.
Intervention: Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low.
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
- •Plaque psoriasis (primarily)
- •Treatment for at least 6 months with IL23 or IL17 inhibitor in a normal dose (dose advised by the label)
- •PASI≤ 5 at inclusion and in previous 6 months (if no PASI scores are available, it should be clear from the patient record that psoriasis was clear/almost clear in previous 6 months).
- •DLQI ≤ 5 at inclusion
排除标准
- •Another indication than plaque psoriasis as the main indication for biologic use (e.g. patient receives biologic for rheumatoid arthritis as the main indication).
- •Concomitant use of systemic immunosuppressants other than methotrexate or acitretin (e.g. prednisone, cyclosporine etc).
- •Severe comorbidities with short life-expectancy (e.g. metastasized tumor).
- •Presumed inability to follow the study protocol.
研究组 & 干预措施
Dose reduction
Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low.
干预措施: Secukinumab (Drug)
Dose reduction
Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low.
干预措施: Ixekizumab (Drug)
Dose reduction
Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low.
干预措施: Brodalumab (Drug)
Dose reduction
Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low.
干预措施: Guselkumab (Drug)
Dose reduction
Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low.
干预措施: Risankizumab (Drug)
Dose reduction
Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low.
干预措施: Tildrakizumab (Drug)
Dose reduction
Dose reduction by interval prolongation in 2 steps to a maximum decrease of 50% of the original dose when disease activity (PASI) and quality of life index (DLQI) remain low.
干预措施: Bimekizumab (Drug)
Normal dose
Patients will continue treatment with the normal/maintenance dose of the biologicals.
干预措施: Secukinumab (Drug)
Normal dose
Patients will continue treatment with the normal/maintenance dose of the biologicals.
干预措施: Ixekizumab (Drug)
Normal dose
Patients will continue treatment with the normal/maintenance dose of the biologicals.
干预措施: Brodalumab (Drug)
Normal dose
Patients will continue treatment with the normal/maintenance dose of the biologicals.
干预措施: Guselkumab (Drug)
Normal dose
Patients will continue treatment with the normal/maintenance dose of the biologicals.
干预措施: Risankizumab (Drug)
Normal dose
Patients will continue treatment with the normal/maintenance dose of the biologicals.
干预措施: Tildrakizumab (Drug)
Normal dose
Patients will continue treatment with the normal/maintenance dose of the biologicals.
干预措施: Bimekizumab (Drug)
结局指标
主要结局
Non-inferiority of the incidence proportion of persistent flares (Psoriasis Area and Severity Index (PASI) >5 for ≥ 3 months).
时间窗: 18 months
次要结局
- Whether other anti-psoriatic medication will be initiated in participants during the study period (18 months).(18 months)
- Drug trough levels of each included drug, measured in blood serum samples which will be collected from participants at each 3-montly time point.(18 months)
- Utilities, derived from EuroQoL 5 Dimensions (EQ-5D-5L) questionnaires, which will be measured at each 3-montly time point.(18 months)
- Psoriasis disease activity, measured with the Psoriasis Area and Severity Index (PASI) at each 3-monthly study visit.(18 months)
- Dermatology-related quality of life as measured with the Dermatology Life Quality Index (DLQI) at each 3-montly study visit.(18 months)
- Whether participants will have successful DR after 12 and 18 months, defined as using a lower dose than the normal dose and PASI ≤ 5.(18 months)
- Whether participants will have short disease flares throughout the study period (18 months), defined as a PASI > 5 at one time point.(18 months)
- Whether participants will have serious adverse events (SAE) and adverse events of special interest (AEoSI) during the study period.(18 months)
- Anti-drug antibody levels of each included drug, measured in blood serum samples which will be collected from participants at each 3-montly time point.(18 months)
- Loss of productivity and presenteeism of participants, as measured with the iMTA Productivity Cost Questionnaire (PCQ) at each 3-monthly time point. Scores will be used to calculate direct medicals costs and non-medical costs.(18 months)
- Health status of participants, assessed by using the Short Form 36 (SF-36) version 2 questionnaire at every 3-monthly time point.(18 months)
- Volumes of care, as measured with the iMTA Medical Consumption Questionnaire (MCQ) at each 3-monthly time point. Scores will be used to calculate direct medicals costs and non-medical costs.(18 months)