Department of Medicine, Division of Dermatology and Venereology, Karolinska Institute, Stockholm, Sweden.
Dermatologikum Hamburg GmbH, Hamburg, Germany.
BMJ Open. 2021 Sep 13;11(9):e049822. doi: 10.1136/bmjopen-2021-049822.
Guselkumab is an interleukin (IL)-23 pathway blocker with proven efficacy in patients with moderate-to-severe plaque psoriasis. Early intervention with guselkumab may result in changes to the clinical disease course versus later intervention.
Here we present the rationale and design of a phase 3b, randomised, double-blind, multicentre study (GUIDE), comparing treatment effects of guselkumab in patients with short (≤2 years) or longer (>2 years) duration of plaque-type psoriasis, measured from first appearance of psoriatic plaques. Participants achieving skin clearance (Psoriasis Area and Severity Index (PASI)=0) by week 20 and maintaining complete clearance at week 28 visit ('super-responders' (SRe)) will be randomised to continue approved maintenance dosing every 8 weeks (q8w) versus an investigational maintenance dosing interval of 16 weeks (q16w) until week 68. Primary endpoint: proportion of participants in the q8w vs q16w arms with absolute PASI <3 at week 68. Participants with PASI <3 at week 68 will be withdrawn from guselkumab treatment for up to 48 weeks. Participants not achieving SRe criteria (non-SRe) will remain in the study with q8w guselkumab dosing through week 68. Additional to serum samples obtained from all patients, skin biopsies and whole-blood samples will be taken from SRe and non-SRe participants at various time points in optional substudies. Analyses include: genetics; immunophenotyping (fluorescence-activated cell sorting); gene and protein expression profiling; immunohistology. By merging clinical endpoints with mechanistic findings, this study aims to elucidate how IL-23 blockade with guselkumab can modify the disease course by altering molecular and cellular drivers that cause relapse after treatment withdrawal, particularly among SRe.
Approval obtained from ethics committee Medical Council Hamburg, Germany (PVN5925). GUIDE is compliant with the Declaration of Helsinki.
Registered at ClinicalTrials.gov (NCT03818035). All primary endpoint results (prespecified analyses) will be submitted to peer-reviewed, international journals within 18 months after primary completion date.
古塞库单抗是一种白细胞介素（IL）-23 通路阻断剂，已被证实可有效治疗中重度斑块型银屑病患者。早期使用古塞库单抗治疗可能会改变临床疾病进程，与后期治疗相比。
在这里，我们介绍了一项 3b 期、随机、双盲、多中心研究（GUIDE）的原理和设计，该研究比较了古塞库单抗治疗斑块型银屑病患者的治疗效果，这些患者的银屑病斑块首次出现的时间从 2 年（≤2 年）或更长时间（>2 年）。在第 20 周达到皮肤清除（银屑病面积和严重程度指数（PASI）=0）并在第 28 周就诊时保持完全清除的“超级应答者”（SRe）将被随机分配继续接受批准的维持剂量每 8 周（q8w）或研究性维持剂量间隔 16 周（q16w），直到第 68 周。主要终点：第 68 周时，q8w 组和 q16w 组中绝对 PASI <3 的参与者比例。第 68 周时 PASI <3 的参与者将停止使用古塞库单抗治疗长达 48 周。未达到 SRe 标准的（非 SRe）参与者将继续接受 q8w 古塞库单抗治疗，直至第 68 周。除了从所有患者获得的血清样本外，还将在可选的亚研究中从 SRe 和非 SRe 参与者的各个时间点采集皮肤活检和全血样本。分析包括：遗传学；免疫表型（荧光激活细胞分选）；基因和蛋白质表达谱；免疫组织化学。通过将临床终点与机制研究结果相结合，本研究旨在阐明古塞库单抗通过改变导致治疗停药后复发的分子和细胞驱动因素，如何改变疾病进程，特别是在 SRe 中。
已获得德国汉堡医学委员会伦理委员会的批准（PVN5925）。GUIDE 符合赫尔辛基宣言。
已在 ClinicalTrials.gov 注册（NCT03818035）。所有主要终点结果（预定分析）将在主要完成日期后 18 个月内提交给同行评议的国际期刊。
