银屑病新一代生物制剂（IL-17 和 IL-23 抑制剂）剂量减少：一项国际性、实用、多中心、随机、对照、非劣效性研究的研究方案——BeNeBio 研究。
Dose reduction of the new generation biologics (IL-17 and IL-23 inhibitors) in psoriasis: study protocol for an international, pragmatic, multicenter, randomized, controlled, non-inferiority study-the BeNeBio study.
机构信息
Radboud University Medical Center, Department of Dermatology, Rene Descartesdreef 1, 6525GL, Nijmegen, The Netherlands.
Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
出版信息
Trials. 2021 Oct 16;22(1):707. doi: 10.1186/s13063-021-05681-z.
BACKGROUND
Psoriasis is a chronic immune-mediated inflammatory skin disease for which biologics are effective treatments. Dose reduction (DR) of the first generation biologics seems a promising way for more efficient use of expensive biologics. A substantial part of patients on tumor necrosis factor (TNF)-alfa inhibitors and ustekinumab could successfully lower their dose, after following a tightly controlled DR strategy. The objective of this study is to assess whether controlled DR of interleukin (IL)-17 and IL-23 inhibitors in psoriasis patients with low disease activity is non-inferior (NI) to usual care (UC).
METHODS
This is an international, prospective, multicenter, pragmatic, randomized, non-inferiority trial. A total of 244 patients with stable low disease activity (Psoriasis Area and Severity Index (PASI) ≤ 5) for at least 6 months and using secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, or tildrakizumab in the standard dose, together with stable low disease activity, defined as a PASI ≤ 5 and Dermatology Life Quality Index (DLQI) ≤ 5 at the moment of inclusion, will be randomized 2:1 to DR or UC. In the DR group, dosing intervals will be prolonged stepwise to achieve 66% and 50% of the original dose. Disease activity is monitored every 3 months by PASI and DLQI. In case of disease flare (i.e., PASI and/or DLQI increase), treatment is adjusted to the previous effective dose. The primary outcome is the incidence proportion of persistent flares (PASI > 5 for ≥ 3 months), which will be compared between arms. Secondary outcomes include proportion of patients with successful DR, (course of) PASI and DLQI, serious adverse events (SAEs), health-related quality of life, costs, and pharmacokinetic profile. Outcomes of DR will be compared to UC.
DISCUSSION
With this study, we aim to assess whether DR of IL-17 and IL-23 inhibiting biologics can be achieved for psoriasis patients with low disease activity, without losing disease control. Reducing the dose may lead to more efficient use of biologics.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04340076 . Registered on April 9 2020.
背景
银屑病是一种慢性免疫介导的炎症性皮肤病，生物制剂对此有效。减少第一代生物制剂的剂量（DR）似乎是一种更有效地利用昂贵生物制剂的有前途的方法。在遵循严格控制 DR 策略后，相当一部分接受肿瘤坏死因子（TNF）-α抑制剂和乌司奴单抗治疗的患者能够成功降低剂量。本研究的目的是评估在疾病活动度低的银屑病患者中，白细胞介素（IL）-17 和 IL-23 抑制剂的控制 DR 是否不劣于（NI）常规护理（UC）。
方法
这是一项国际、前瞻性、多中心、实用、随机、非劣效性试验。共有 244 名病情稳定（银屑病面积和严重程度指数（PASI）≤5）至少 6 个月的患者接受司库奇尤单抗、依奇珠单抗、布罗达umab、古塞库单抗、瑞莎珠单抗或替西珠单抗标准剂量治疗，且在纳入时疾病活动度稳定（定义为 PASI≤5，皮肤病生活质量指数（DLQI）≤5），将被随机分为 2:1 接受 DR 或 UC。在 DR 组中，剂量间隔将逐步延长，以达到原始剂量的 66%和 50%。每 3 个月通过 PASI 和 DLQI 监测疾病活动度。如果出现疾病发作（即 PASI 和/或 DLQI 增加），则调整治疗至先前有效的剂量。主要结局是持续发作（PASI >5 持续≥3 个月）的发生率比例，将在两组之间进行比较。次要结局包括成功 DR 的患者比例、（PASI 和/或 DLQI 的）病程、严重不良事件（SAE）、健康相关生活质量、成本和药代动力学特征。DR 的结果将与 UC 进行比较。
讨论
通过这项研究，我们旨在评估对于疾病活动度低的银屑病患者，是否可以实现白细胞介素（IL）-17 和 IL-23 抑制生物制剂的 DR，而不会失去疾病控制。减少剂量可能会导致更有效地利用生物制剂。
试验注册
ClinicalTrials.gov NCT04340076。于 2020 年 4 月 9 日注册。
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