التفاصيل البيبلوغرافية
| العنوان: |
Efficacy and Safety of Tofacitinib in Patients with Polymyalgia Rheumatica (EAST PMR): An open-label randomized controlled trial |
| المؤلفون: |
Ma, Xinlei, Yang, Fan, Wu, Jinzhi, Xu, Bei, Jiang, Mengdi, Sun, Yiduo, Sun, Chuanying, Yu, Ye, Xu, Danyi, Xiao, Lanlan, Ren, Chunyun, Chen, Chunyan, Ye, Zi, Liang, Junyu, Lin, Jin, Chen, Weiqian |
| المساهمون: |
Natural Science Foundation of China, Key Technologies Research and Development Program |
| المصدر: |
PLOS Medicine ; volume 20, issue 6, page e1004249 ; ISSN 1549-1676 |
| بيانات النشر: |
Public Library of Science (PLoS) |
| سنة النشر: |
2023 |
| المجموعة: |
PLOS Publications (via CrossRef) |
| الوصف: |
Background Polymyalgia rheumatica (PMR) is a common inflammatory disease in elderly persons whose mechanism of pathogenesis has not been elucidated. Glucocorticoids are the main first-line treatments but result in numerous side effects. Therefore, there is a need to explore pathogenetic factors and identify possible glucocorticoid-sparing agents. We aimed to study the pathogenetic features of the disease and assess the efficacy and safety of Janus tyrosine kinase (JAK)-inhibitor tofacitinib in patients with PMR. Methods and findings We recruited treatment-naïve PMR patients from the First Affiliated Hospital, Zhejiang University School of Medicine, between September 2020 and September 2022. In the first cohort, we found that the gene expression patterns of peripheral blood mononuclear cells (PBMCs) in 11 patients (10 female, 1 male, age 68.0 ± 8.3) with newly diagnosed PMR were significantly different from 20 healthy controls (17 female, 3 male, age 63.7 ± 9.8) by RNA sequencing. Inflammatory response and cytokine–cytokine receptor interaction were the most notable pathways affected. We observed marked increases in expression of IL6R, IL1B, IL1R1, JAK2, TLR2, TLR4, TLR8, CCR1, CR1, S100A8, S100A12, and IL17RA, which could trigger JAK signaling. Furthermore, tofacitinib suppressed the IL-6R and JAK2 expression of CD4 + T cells from patients with PMR in vitro . In the second cohort, patients with PMR were randomized and treated with tofacitinib or glucocorticoids (1/1) for 24 weeks. All PMR patients underwent clinical and laboratory examinations at 0, 4, 8, 12, 16, 20, and 24 weeks, and PMR activity disease scores (PMR-AS) were calculated. The primary endpoint was the proportion of patients with PMR-AS ≤10 at weeks 12 and 24. Secondary endpoints: PMR-AS score, c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) at weeks 12 and 24. Thirty-nine patients with newly diagnosed PMR received tofacitinib, and 37 patients received glucocorticoid. Thirty-five patients (29 female, 6 male, age 64.4 ± 8.4) and ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1371/journal.pmed.1004249 |
| الإتاحة: |
https://doi.org/10.1371/journal.pmed.1004249Test |
| حقوق: |
http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.C2CE747C |
| قاعدة البيانات: |
BASE |
