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托法替尼治疗中国人瘢痕疙瘩的开放性、非对照、单臂临床试验

An Open-Label, Uncontrolled, Single-Arm Clinical Trial of Tofacitinib, an Oral JAK1 and JAK3 Kinase Inhibitor, in Chinese Patients with Keloid.

机构信息

The First School of Clinical Medicine, Southern Medical University, Guangzhou, China,

Dermatology Hospital, Southern Medical University, Guangzhou, China,

出版信息

Dermatology. 2023;239(5):818-827. doi: 10.1159/000532064. Epub 2023 Aug 29.

Abstract

BACKGROUND

The keloid treatment is still a thorny and complicated clinical problem, especially in multiple keloids induced by wound, severe burn, ethnic background or cultural behaviors, or unexplained skin healing. Mainstream treatments have limited efficacy in treating multiple keloids. As no oral treatment with painlessness and convenience is available, oral treatment strategies should be formulated.

OBJECTIVES

This study aimed to investigate the efficacy and therapeutic mechanism of oral tofacitinib in keloid patients.

METHODS

We recruited the 7 patients with keloid scars and prescribed 5 mg of tofacitinib twice a day orally with a maximum follow-up of 12 weeks. The Patient and Observer Scar Assessment Scale (POSAS), the Vancouver scar scale (VSS), ANTERA 3D camera, and the DUB Skin Scanner 75 were used to assess the characteristics of the lesion. Immunohistochemistry was performed to evaluate collagen synthesis, proliferation, and relative molecular pathways. Moreover, the effects of tofacitinib were assessed on keloid fibroblast in vitro.

RESULTS

After 12 weeks of oral tofacitinib, significant improvement in POSAS, VSS, and Dermatology Life Quality Index (DLQI) scores was observed (p < 0.05). The volume, lesion height, and dermis thickness of the keloid decreased (p < 0.05). Moreover, significant decreases in the expression of collagen I, Ki67, p-STAT 3, and p-SMAD2 were observed after 12 weeks of administration. In vitro experiments suggested that tofacitinib treatment inhibits fibroblast proliferation and collagen I synthesis via suppression of STAT3 and SMAD2 pathway.

CONCLUSION

Tofacitinib, a new candidate oral drug for keloid, could reduce keloid lesion volume by inhibiting collagen synthesis and inhibiting fibroblast proliferation, and alleviate itch and pain to obtain a better life quality.

摘要

背景

瘢痕疙瘩的治疗仍然是一个棘手且复杂的临床问题,尤其是在由创伤、严重烧伤、种族背景或文化行为或不明原因的皮肤愈合引起的多发性瘢痕疙瘩中。主流治疗方法在治疗多发性瘢痕疙瘩方面疗效有限。由于没有无痛且方便的口服治疗方法,因此应制定口服治疗策略。

目的

本研究旨在探讨口服托法替尼治疗瘢痕疙瘩患者的疗效和治疗机制。

方法

我们招募了 7 名瘢痕疙瘩患者,每天口服 5mg 托法替尼两次,最大随访时间为 12 周。使用患者和观察者瘢痕评估量表(POSAS)、温哥华瘢痕量表(VSS)、ANTERA 3D 相机和 DUB 皮肤扫描仪 75 评估病变特征。进行免疫组织化学染色以评估胶原合成、增殖和相对分子途径。此外,还评估了托法替尼对体外瘢痕疙瘩成纤维细胞的作用。

结果

口服托法替尼 12 周后,POSAS、VSS 和皮肤病生活质量指数(DLQI)评分显著改善(p < 0.05)。瘢痕疙瘩的体积、病变高度和真皮厚度均减小(p < 0.05)。此外,治疗 12 周后,I 型胶原、Ki67、p-STAT3 和 p-SMAD2 的表达显著下降。体外实验表明,托法替尼通过抑制 STAT3 和 SMAD2 通路抑制成纤维细胞增殖和 I 型胶原合成来治疗瘢痕疙瘩。

结论

托法替尼是一种新型候选口服药物,可通过抑制胶原合成和抑制成纤维细胞增殖来减少瘢痕疙瘩病变体积,并缓解瘙痒和疼痛,从而获得更好的生活质量。

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