Article ; Online: An Open-Label, Uncontrolled, Single-Arm Clinical Trial of Tofacitinib, an Oral JAK1 and JAK3 Kinase Inhibitor, in Chinese Patients with Keloid.
Dermatology (Basel, Switzerland)
2023 Volume 239, Issue 5, Page(s) 818–827
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 ... ...
| 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. |
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| MeSH term(s) | Humans ; Collagen ; East Asian People ; Janus Kinase 1 ; Janus Kinase 3/antagonists & inhibitors ; Keloid/pathology ; Skin/pathology ; Treatment Outcome |
| Chemical Substances | Collagen (9007-34-5) ; JAK1 protein, human (EC 2.7.10.2) ; JAK3 protein, human (EC 2.7.10.2) ; Janus Kinase 1 (EC 2.7.10.2) ; Janus Kinase 3 (EC 2.7.10.2) ; tofacitinib (87LA6FU830) |
| Language | English |
| Publishing date | 2023-08-29 |
| Publishing country | Switzerland |
| Document type | Clinical Trial ; Journal Article |
| ZDB-ID | 1099692-8 |
| ISSN | 1421-9832 ; 1018-8665 |
| ISSN (online) | 1421-9832 |
| ISSN | 1018-8665 |
| DOI | 10.1159/000532064 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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