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Researchers Identify Biomarker for Inflammation, MTX Treatment Response in PsA

MicroRNA-21-5p (miR-21-5p) expression is upregulated in patients with psoriatic arthritis (PsA), which suggests that the molecule may be a potential biomarker of inflammation in psoriatic disease, according to findings from a new study presented at the 2019 American College of Rheumatology (ACR)/Association of Rheumatology Professionals (ARP) Annual Meeting.

Additionally, the findings showed regulation patterns of miR-21-5p expression in patients with PsA who received oral or subcutaneous methotrexate (MTX) treatment, which suggested that the molecule is a potential biomarker for response to MTX treatment.


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The researchers had previously demonstrated that miR-21-5p was upregulated in patients with PsA compared with patients with psoriasis without arthritis and compared with control participants. Additionally, they demonstrated that miR-21-5p modulated inflammation through the interleukin 17/interleukin 23 axis and the C-X-C motif chemokine ligand 10 gene (CXCL10).

For this study, the researchers sought to validate the previous study results in a new set of patients; examine miR-21-5p expression before and after 24 weeks of MTX treatment; and determine whether miR-21-5p expression was different based on the route of MTX administration.

Rohan Machhar, from the Krembil Research Institute in Toronto, Canada, and colleagues collected serum and whole blood RNA samples from 40 patients with early PsA, 40 patients with psoriasis without PsA, 15 patients with PsA before and after they had received 24 weeks of treatment with MTX, and 40 healthy control participants.

An additional 15 samples from patients with PsA were collected to compare oral MTX with subcutaneous MTX.

Results showed that miR-21-5p was upregulated in patients with PsA compared with patients with psoriasis without PsA; this validated the results of the previous studies.

The researchers observed a correlation between miR-21-5p expression and swollen joint count and actively inflamed joint counts in patients with PsA. The miR-21-5p expression was significantly down-regulated 24 weeks post-MTX treatment in 12 patients and correlated with actively inflamed joint count, swollen joint, tender joint, and clinical Disease Activity in Psoriatic Arthritis (cDAPSA) score.

Three patients showed an upregulation of miR-21-5p; these patients had treatment escalation at subsequent visit.

Among patients who had received subcutaneous MTX, there was a significant downregulation of miR-21-5p and significant correlation with actively inflamed joint counts and cDAPSA. No downregulation of miR-21-5p expression was observed in patients who had received oral MTX. The average MTX dose was 15.5 mg per week and was not significantly different in both groups.

“We have determined a role of miR-21-5p as a potential biomarker for inflammation in psoriatic disease and response to methotrexate treatment,” the researchers concluded. “MiR-21-5p levels appear to decrease in patients taking subcutaneous but not oral MTX.”

—Melinda Stevens

Reference:

Machhar R, Ye J(Y), Pollock R, Gladman D. miR-21-5p expression as a marker of treatment response in psoriatic arthritis patients [abstract 1909]. Arthritis Rheumatol. 2019;71(suppl 10). Presented at: 2019 ACR/ARP Annual Meeting; November 8-13, 2019; Atlanta, GA. https://acrabstracts.org/abstract/mir-21-5p-expression-as-a-marker-of-treatment-response-in-psoriatic-arthritis-patients/. Accessed November 6, 2019.