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.
Trials. 2021 Oct 16;22(1):707. doi: 10.1186/s13063-021-05681-z.
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).
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.
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.
ClinicalTrials.gov NCT04340076 . Registered on April 9 2020.
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）。
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。
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。
ClinicalTrials.gov NCT04340076。于 2020 年 4 月 9 日注册。
