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比较德瓦鲁单抗与甲氨蝶呤治疗强效皮质类固醇外用治疗失败的外阴扁平苔藓患者的疗效和安全性:一项单中心、双盲、随机对照试验研究方案。

The efficacy and safety of deucravacitinib compared to methotrexate, in patients with vulvar lichen planus who have failed topical therapy with potent corticosteroids: a study protocol for a single-centre double-blinded randomised controlled trial.

机构信息

Department of Dermatology, Royal North Shore Hospital, Reserve Rd, St Leonards, New South Wales, Australia.

The University of Sydney, Northern Clinical School, St Leonards, New South Wales, Australia.

出版信息

Trials. 2024 Mar 12;25(1):181. doi: 10.1186/s13063-024-08022-y.


DOI:10.1186/s13063-024-08022-y
PMID:38475894
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10929110/
Abstract

BACKGROUND: Vulvar lichen planus (VLP) is a chronic vulvar dermatosis that is difficult to treat and can severely impair quality of life in the absence of adequate treatment. There is a lack of high-quality evidence to direct therapy for VLP. This randomised controlled trial will be the first double-blinded study comparing systemic treatments in VLP and aims to investigate the safety and efficacy of deucravacitinib compared to methotrexate, in patients with VLP who have failed treatment with potent topical corticosteroids. METHODS: A total of 116 women aged ≥ 18 years with moderate to severe VLP (Genital Erosive Lichen Planus (GELP) score ≥ 5) will be recruited. All participants will initially be treated with Diprosone® OV daily, and their outcome will be assessed using the GELP score. At 8 weeks' follow-up, responders (GELP < 5) will be continued on Diprosone® OV. Non-responders (GELP ≥ 5) will be randomised 1:1 in a blinded fashion to receive (i) methotrexate 10 mg weekly + placebo tablet twice daily + folic acid 5 mg weekly or (ii) deucravacitinib 6 mg twice daily + placebo tablet weekly + folic acid 5 mg weekly. The primary endpoint is the difference in the mean change of GELP scores from baseline to week 32 between deucravacitinib and methotrexate groups. DISCUSSION: High-quality evidence guiding the management of women with VLP is lacking. Once completed, this will be the first double-blinded RCT to compare systemic treatments in VLP. The results of this study will provide valuable, high-quality data to guide second-line therapy options for VLP that is recalcitrant to potent topical corticosteroids. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12623000682640. Registered on 26 June 2023.

摘要

背景:外阴硬化性苔藓(VLP)是一种难以治疗的慢性外阴皮肤病,如果没有足够的治疗,会严重影响生活质量。目前缺乏高质量的证据来指导 VLP 的治疗。这项随机对照试验将是第一项比较 VLP 系统治疗的双盲研究,旨在研究与甲氨蝶呤相比,在接受强效外用皮质类固醇治疗失败的 VLP 患者中,德夸鲁瓦替尼的安全性和有效性。

方法:共招募 116 名年龄≥18 岁、患有中重度 VLP(外阴侵蚀性苔藓评分[GELP]≥5)的女性。所有参与者最初将每天接受 Diprosone® OV 治疗,并使用 GELP 评分评估他们的疗效。在 8 周的随访中,GELP<5 的患者将继续接受 Diprosone® OV 治疗。GELP≥5 的非应答者将以 1:1 的比例进行盲法随机分组,分别接受(i)甲氨蝶呤 10mg 每周+安慰剂片剂每日两次+叶酸 5mg 每周或(ii)德夸鲁瓦替尼 6mg 每日两次+安慰剂片剂每周+叶酸 5mg 每周。主要终点是德夸鲁瓦替尼组和甲氨蝶呤组从基线到第 32 周时 GELP 评分的平均变化差异。

讨论:缺乏指导 VLP 女性管理的高质量证据。一旦完成,这将是第一项比较 VLP 系统治疗的双盲 RCT。该研究的结果将为指导对强效外用皮质类固醇耐药的 VLP 的二线治疗选择提供有价值的高质量数据。

试验注册:澳大利亚和新西兰临床试验注册中心 ACTRN12623000682640。于 2023 年 6 月 26 日注册。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aa7/10929110/c2eb2dea17a0/13063_2024_8022_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aa7/10929110/00c235a07722/13063_2024_8022_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aa7/10929110/c2eb2dea17a0/13063_2024_8022_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aa7/10929110/00c235a07722/13063_2024_8022_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aa7/10929110/c2eb2dea17a0/13063_2024_8022_Fig2_HTML.jpg

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引用本文的文献

[1]
SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials.

BMJ. 2025-4-28

[2]
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[3]
Translational Research in Oral Lichen Planus: From Laboratory Discoveries to Clinical Applications.

Cureus. 2024-10-14

[4]
Vulvar Inflammatory Dermatoses: New Approaches for Diagnosis and Treatment.

Cutis. 2024-8

本文引用的文献

[1]
Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 Program fOr Evaluation of TYK2 inhibitor psoriasis second trial.

J Am Acad Dermatol. 2023-1

[2]
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Australas J Dermatol. 2022-11

[3]
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J Am Acad Dermatol. 2023-1

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Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis.

Ann Rheum Dis. 2022-6

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Successful treatment of vulvovaginal lichen planus with tildrakizumab: A case series of 24 patients.

Australas J Dermatol. 2022-5

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Apremilast for genital erosive lichen planus in women (the AP-GELP Study): study protocol for a randomised placebo-controlled clinical trial.

Trials. 2021-7-20

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Br J Dermatol. 2021-7

[8]
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Australas J Dermatol. 2021-5

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Australas J Dermatol. 2020-11

[10]
Vulvar malignancy in biopsy-proven vulval lichen planus: A retrospective review of 105 cases.

Australas J Dermatol. 2020-11

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