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替西罗莫司单抗治疗中度至重度斑块状银屑病日本患者的疗效和安全性:一项 64 周 3 期研究(reSURFACE 1)的结果。

Efficacy and safety of tildrakizumab in Japanese patients with moderate to severe plaque psoriasis: Results from a 64-week phase 3 study (reSURFACE 1).

机构信息

NTT Medical Center Tokyo, Tokyo, Japan.

The Jikei University School of Medicine, Tokyo, Japan.

出版信息

J Dermatol. 2021 Jun;48(6):853-863. doi: 10.1111/1346-8138.15789. Epub 2021 Feb 25.


DOI:10.1111/1346-8138.15789
PMID:33630387
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8247960/
Abstract

Tildrakizumab is a high-affinity, humanized immunoglobulin G1κ, anti-interleukin-23p19 monoclonal antibody recently approved in Japan for treatment of plaque psoriasis. We report results from Japanese patients treated with tildrakizumab in the multinational, randomized, double-blind, placebo-controlled reSURFACE 1 study (clinicaltrials.gov NCT01722331). Adults with moderate to severe plaque psoriasis were randomized (2:2:1) to receive subcutaneous tildrakizumab 100 or 200 mg or placebo every 12 weeks. Placebo recipients were rerandomized to tildrakizumab 100 or 200 mg at week 12. The global study coprimary endpoints were the proportions of patients achieving 75% improvement from baseline Psoriasis Area and Severity Index (PASI 75) and Physician Global Assessment (PGA) response (0/1 with ≥2 grade reduction from baseline) at week 12. Analyses included 158 Japanese patients randomized to tildrakizumab 100 (n = 64) or 200 mg (n = 62) or placebo (n = 32). Japanese patients had higher mean baseline body surface area involvement and PASI versus all reSURFACE 1 patients. At week 12, significantly more Japanese patients receiving tildrakizumab 100 and 200 mg versus placebo achieved PASI 75 (54.7% and 54.8% vs 6.3%, respectively, both nominal p < 0.001) and PGA 0/1 response (54.7% and 56.5% vs 9.4%, respectively, both nominal P < 0.001). Response rates increased over time with maximal efficacy after 22-28 weeks; >80% of patients achieving PASI 75 or PASI 90 at week 28 and continuing tildrakizumab treatment at the same dose maintained response at week 64. From baseline to week 28, absolute PASI decreased from >12 in all patients to ≤2 in >40% and ≤3 in >50% of patients receiving tildrakizumab. Tildrakizumab was generally well tolerated with an adverse event profile similar to that of placebo. Tildrakizumab treatment was associated with durable efficacy in Japanese patients with moderate to severe plaque psoriasis despite greater baseline disease severity versus the global reSURFACE 1 population.

摘要

替西单抗是一种高亲和力的人源化 IgG1κ 抗白细胞介素-23p19 单克隆抗体,最近在日本被批准用于治疗斑块状银屑病。我们报告了在多中心、随机、双盲、安慰剂对照的 reSURFACE 1 研究(clinicaltrials.gov NCT01722331)中接受替西单抗治疗的日本患者的结果。中度至重度斑块状银屑病患者按 2:2:1 的比例随机分配接受替西单抗 100 或 200mg 或安慰剂,每 12 周一次。安慰剂组患者在第 12 周时被重新随机分配至替西单抗 100 或 200mg。该全球研究的主要终点是第 12 周时达到银屑病面积和严重程度指数(PASI 75)和医生整体评估(PGA)应答(从基线改善≥75%,且 PGA 评分 0/1 且至少降低 2 级)的患者比例。分析包括 158 名日本患者,随机分配至替西单抗 100mg(n=64)、200mg(n=62)或安慰剂(n=32)。与所有 reSURFACE 1 患者相比,日本患者的基线体表面积受累和 PASI 更高。在第 12 周时,与安慰剂相比,接受替西单抗 100mg 和 200mg 治疗的日本患者中,达到 PASI 75(分别为 54.7%和 54.8%,均为名义 p<0.001)和 PGA 0/1 应答(分别为 54.7%和 56.5%,均为名义 P<0.001)的患者比例显著更高。应答率随时间增加,在 22-28 周时达到最大疗效;在第 28 周时,超过 80%的患者达到 PASI 75 或 PASI 90,并且继续以相同剂量接受替西单抗治疗的患者在第 64 周时维持应答。从基线到第 28 周,所有患者的绝对 PASI 从>12 下降到>40%的患者≤2,>50%的患者≤3。替西单抗的安全性与安慰剂相似,耐受性良好。尽管与全球 reSURFACE 1 人群相比,日本患者的基线疾病严重程度更高,但替西单抗治疗与中度至重度斑块状银屑病患者的持久疗效相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b1d/8247960/73222211a765/JDE-48-853-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b1d/8247960/292d77f75f05/JDE-48-853-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b1d/8247960/fb7c037eeba3/JDE-48-853-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b1d/8247960/b48a5d05211a/JDE-48-853-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b1d/8247960/73222211a765/JDE-48-853-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b1d/8247960/292d77f75f05/JDE-48-853-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b1d/8247960/fb7c037eeba3/JDE-48-853-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b1d/8247960/b48a5d05211a/JDE-48-853-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b1d/8247960/73222211a765/JDE-48-853-g001.jpg

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引用本文的文献

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Dermatol Ther (Heidelb). 2025-6

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[3]
Indirect comparison of deucravacitinib and other systemic treatments for moderate to severe plaque psoriasis in Asian populations: A systematic literature review and network meta-analysis.

J Dermatol. 2024-12

[4]
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本文引用的文献

[1]
A head-to-head comparison of ixekizumab vs. guselkumab in patients with moderate-to-severe plaque psoriasis: 24-week efficacy and safety results from a randomized, double-blinded trial.

Br J Dermatol. 2021-6

[2]
Efficacy and safety of risankizumab vs. secukinumab in patients with moderate-to-severe plaque psoriasis (IMMerge): results from a phase III, randomized, open-label, efficacy-assessor-blinded clinical trial.

Br J Dermatol. 2021-1

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J Dermatol. 2020-1-8

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Br J Dermatol. 2020-6

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Lancet. 2019-8-8

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Lancet. 2019-7-4

[7]
Efficacy and safety of risankizumab in Japanese patients with moderate to severe plaque psoriasis: Results from the SustaIMM phase 2/3 trial.

J Dermatol. 2019-6-25

[8]
Long-term efficacy and safety of tildrakizumab for moderate-to-severe psoriasis: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2) through 148 weeks.

Br J Dermatol. 2020-3

[9]
Patient preference for biologic treatments of psoriasis in Japan.

J Dermatol. 2019-4-15

[10]
Guselkumab, an anti-interleukin-23 monoclonal antibody, for the treatment of moderate to severe plaque-type psoriasis in Japanese patients: Efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled study.

J Dermatol. 2018-6-15

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