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UTS2 Expression Can Be Used to Identify Patients With RA Who Will Respond to Tocilizumab
June 8, 2021

By Erika Powers

VIRTUAL -- June 8, 2021 -- Patients with early rheumatoid arthritis (RA) who received treatment with tocilizumab had gene expression differences at baseline, in both whole blood and peripheral blood mononuclear cells (PBMC) RNA samples, that predicted response to tocilizumab, according to a study presented at the Virtual 2021 Annual Meeting of the European League Against Rheumatism (EULAR).

“Tocilizumab has shown to be effective as monotherapy in early rheumatoid arthritis,” said Ittai Muller, Amsterdam UMC, Amsterdam, the Netherlands. “However, approximately a third of patients inadequately respond to therapy and the biological mechanisms underlying lack of efficacy for tocilizumab remain elusive.”

When the researchers analysed blood samples from 2 cohorts of patients with RA before initiating tocilizumab treatment, they found that several genes were differentially expressed at baseline between responders and non-responders to tocilizumab therapy at 6 months.

“Whole blood differential gene expression analysis showed 2 significantly higher expressed genes in tocilizumab non-responders -- urotensin 2 [UTS2] and caveolin-1,” reported Dr. Muller. “Most notably, UTS2 expression was significantly higher in tocilizumab non-responders in both whole blood as well as PBMC cohorts.”

Gene ontology enrichment analysis revealed no distinct gene ontology or interleukin 6 receptor-related pathway(s) that were significantly different between tocilizumab-responders and non-responders.

“UTS2 could be a promising target for further analyses as a potential predictive biomarker for tocilizumab response in patients with RA in combination with clinical parameters,” said Dr. Muller.

The first cohort included 21 patients, previously treated with disease-modifying antirheumatic drugs. RNA sequencing was performed on baseline whole blood and differential gene expression profiles were measured between responders (n = 14) and non-responders (n = 7). For external replication, a second cohort of 95 treatment-naïve patients receiving tocilizumab monotherapy was conducted. Patients were part of the randomised U-Act-Early trial, and included 84 responders and 11 non-responders. In this cohort, RNA sequencing was conducted on baseline PBMC.

[Presentation title: Identification of Differentially Expressed Genes in Early Rheumatoid Arthritis Patients Responding to Tocilizumab. Abstract OP0021]