Efficacy and Safety of Tofacitinib in Patients with Polymyalgia Rheumatica (EAST PMR): An open-label randomized controlled trial
Abstract
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…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 37 participants or records.
Read the paper
Related studies
- Safety and efficacy of COVID‐19 vaccines: A systematic review and meta‐analysis of controlled and randomized clinical trials
- Accuracy Comparison between Robot-Assisted Dental Implant Placement and Static/Dynamic Computer-Assisted Implant Surgery: A Systematic Review and Meta-Analysis of In Vitro Studies
- Determinants of passive antibody efficacy in SARS-CoV-2 infection: a systematic review and meta-analysis
- Cleaning efficacy of EDDY versus ultrasonically-activated irrigation in root canals: a systematic review and meta-analysis
- Bonding Efficacy of Universal Resin Adhesives to Zirconia Substrates: Systematic Review and Meta-Analysis
- In vitro antimicrobial activity of extracts and essential oils of Cinnamomum, Salvia, and Mentha spp. against foodborne pathogens: A meta-analysis study
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.