减少银屑病患者il - 17和il - 23抑制剂的剂量（BeNeBio研究）：一项国际、实用、多中心、随机、对照、非劣效性试验。

IF 15.7 Q1 HEALTH CARE SCIENCES & SERVICES

Lancet Regional Health-Europe Pub Date : 2026-08-01 Epub Date: 2026-06-01 DOI:10.1016/j.lanepe.2026.101721

Juul M.P.A. van den Reek, Charlotte A.M. van Riel, Rani Soenen, Anke Eylenbosch, Lisa Schots, Lara S. van der Schoot, Lynda Grine, Gerjon Hannink, Fabienne Willaert, Tom Hillary, Paula P.M. van Lümig, Pierre-Dominique Ghislain, Paul M. Ossenkoppele, Sven Lanssens, Bas S.P. Prens, Linda Temmerman, Martijn B.A. van Doorn, Ella A.M. van der Voort, Inge Haeck, Janneke Huizinga, Elke M.G.J. de Jong

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引用次数: 0

摘要

背景：白介素（IL）17和IL23抑制剂(i)治疗牛皮癣非常有效，但并非所有患者都需要注册剂量。减少剂量有助于防止不必要的药物接触和降低医疗保健支出。本研究的目的是评估通过逐步延长病程间隔的DR对稳定的低疾病活动度银屑病患者是否有效和安全。方法：这项实用、开放标签、对照、非劣效性随机临床试验在荷兰和比利时的19家（非）学术医院进行。患者被随机分组（2:1），按照随机分配顺序，按生物学因素分层，逐步接受DR或常规护理（UC）。使用注册剂量的IL17i （secukinumab, ixekizumab, bimekizumab, brodalumab）或IL23i （guselkumab, risankizumab, tildrakizumab）稳定的低疾病活动性患者符合条件。在DR中，如果疾病活动允许，注射间隔逐步延长至原始剂量的67.0%和50.0%。主要目的是评估这种DR策略与UC相比在18个月后持续耀斑（牛皮癣面积和严重程度指数（PASI） bbbb5≥3个月）发生率的非劣效性，非劣效性裕度为15.0%。通过意向治疗（ITT）和每个方案（PP）对患者进行分析，并对缺失进行归因。ClinicalTrials.gov标识符NCT04340076；状态:关闭。结果：在2020年6月30日至2023年9月14日期间，纳入244例患者（平均年龄51±15岁，67.0%男性，DR N = 164, UC N = 80）。18个月后，持续耀斑发生率（ITT组DR（4.0%）和UC(1.6%)）的差异为2.4% (95% CI -2.0%至6.8%)，显示DR的非劣效性。未报告与DR相关的严重不良事件/死亡。结论：在控制银屑病患者中，以疾病活动为导向，逐步延长il - 17i和il - 23i的间隔是一种有效且安全的策略，可以减少不必要的昂贵药物暴露。资助：ZonMw（荷兰卫生研究与发展组织）、KCE Trials（比利时卫生保健知识中心）。

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Dose Reduction of IL17 and IL23 Inhibitors in Psoriasis (BeNeBio study): An International, Pragmatic, Multicentre, Randomised, Controlled, Non-Inferiority Trial

Background

Interleukin (IL)17 and IL23 inhibitors (i) for psoriasis are highly effective but not all patients may need the registered dose. Dose reduction (DR) could contribute to prevent unnecessary drug exposure and lower healthcare expenditures. The aim of this study was to evaluate whether DR through stepwise interval prolongation is effective and safe in patients with psoriasis with stable low disease activity.

Methods

This pragmatic, open-label, controlled, non-inferiority randomised clinical trial was performed in 19 (non-)academic hospitals in the Netherlands and Belgium. Patients were randomised (2:1) to stepwise DR or usual care (UC) by block randomisation with random allocation sequence, stratified by biologic. Patients with stable low disease activity on registered dosages of IL17i (secukinumab, ixekizumab, bimekizumab, brodalumab) or IL23i (guselkumab, risankizumab, tildrakizumab) were eligible. In DR, injection intervals were prolonged stepwise to 67.0% and 50.0% of the original dose if disease activity permitted. The primary aim was to assess non-inferiority of this DR strategy compared to UC regarding the incidence proportion of persistent flares (Psoriasis Area and Severity Index (PASI) > 5 for ≥3 months) after 18 months, with a non-inferiority margin of 15.0%. Patients were analysed by intention-to-treat (ITT) and per-protocol (PP) with imputation of missings. ClinicalTrials.gov Identifier NCT04340076; status: closed.

Findings

Between June 30, 2020 and September 14, 2023, 244 patients were included (mean age 51 ± 15 years; 67.0% male; DR N = 164, UC N = 80). After 18 months, a difference of 2.4% (95% CI −2.0% to 6.8%) in incidence proportion of persistent flares (DR (4.0%) and UC (1.6%) in ITT) showed non-inferiority of DR. No serious adverse events/deaths related to DR were reported.

Interpretation

Disease-activity guided, stepwise interval prolongation of IL17i and IL23i in patients with controlled psoriasis is an effective and safe strategy to reduce unnecessary exposure to these expensive drugs.

Funding

ZonMw (the Netherlands Organization for Health Research and Development), KCE Trials (the Belgian Health Care Knowledge Centre).

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来源期刊

Lancet Regional Health-Europe Multiple-

CiteScore

19.90

自引率

1.40%

发文量

260

审稿时长

9 weeks

期刊介绍： The Lancet Regional Health – Europe, a gold open access journal, is part of The Lancet's global effort to promote healthcare quality and accessibility worldwide. It focuses on advancing clinical practice and health policy in the European region to enhance health outcomes. The journal publishes high-quality original research advocating changes in clinical practice and health policy. It also includes reviews, commentaries, and opinion pieces on regional health topics, such as infection and disease prevention, healthy aging, and reducing health disparities.