JAK signaling may be behind polymyalgia rheumatica

Updated on 2024-04-16 17:00:58 18 19

by Lori Solomon

Janus tyrosine kinase (JAK) signaling may be involved in the pathogenesis of polymyalgia rheumatica (PMR), and tofacitinib may be an effective treatment, according to a pilot study published online June 29 in PLOS Medicine.

Xinlei Ma, from Zhejiang University in Hangzhou, China, and colleagues examined pathogenetic features of PMR and assessed the efficacy and safety of the JAK inhibitor tofacitinib in patients with PMR. The analysis included 11 treatment-naive PMR patients and 20 healthy controls. In a second cohort, 76 patients with PMR were randomly assigned to tofacitinib or glucocorticoid treatment in an open-label trial, with 67 completing the 24-week intervention.

The researchers found that gene expression patterns of peripheral blood mononuclear cells in patients with newly diagnosed PMR were significantly different from 20 healthy controls using RNA sequencing. The most notable pathways affected were inflammatory response and cytokine-cytokine receptor interaction, with marked increases in expression of IL6R, IL1B, IL1R1, JAK2, TLR2, TLR4, TLR8, CCR1, CR1, S100A8, S100A12, and IL17RA, which could trigger JAK signaling.

In vitro, tofacitinib suppressed the IL6R and JAK2 expression of CD4⁺T cells from patients with PMR. Among a second cohort of patients with newly diagnosed PMR randomly assigned to tofacitinib or glucocorticoid, all patients in both groups had PMR disease activity scores <10, and C-reactive protein and erythrocyte sedimentation rate were significantly decreased in both groups at weeks 12 and 24, with no severe adverse events.

"We think tofacitinib may have a high response rate in the new diagnosed PMR patients who were naive to glucocorticoid or biological agents," the authors write.

More information: Xinlei Ma et al, Efficacy and Safety of Tofacitinib in Patients with Polymyalgia Rheumatica (EAST PMR): An open-label randomized controlled trial, PLOS Medicine (2023). DOI: 10.1371/journal.pmed.1004249

Journal information: PLoS Medicine

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