The predictive value of serum S100A9 and response to etanercept is not confirmed in a large UK rheumatoid arthritis cohort.

Samantha Louise Smith,Anthony G Wilson,Stephen Eyre,Anne Barton,Darren Plant,Ann W Morgan,John D Isaacs,Kimme Hyrich

doi:10.1093/rheumatology/kew387

Abstract

Objective. The aim was to correlate protein concentrations of S100A9 in pretreatment serum samples with response to the tumour-necrosis factor (TNF) inhibitor drugs etanercept in a large UK replication cohort. Methods. Pretreatment serum samples from patients with RA (n = 236) about to commence treatment with etanercept had S100A9 serum concentration measured using an ELISA. Following the experimental procedure, S100A9 concentrations were analysed with respect to EULAR response. Results. No evidence of association between S100A9 concentration and EULAR response to the TNF-inhibitor biologic drug etanercept was observed following multinomial logistic regression analysis (non-responder vs moderate responder, P = 0.957; and non-responder vs good responder, P = 0.316). Furthermore, no significant associations were observed when correlating pretreatment S100A9 concentrations with clinical parameters of disease activity (P > 0.05). Conclusion. In the largest replication cohort conducted to date, no evidence for association was observed to support the use of S100A9 as a clinical biomarker predictive of response to the TNF-inhibitor biologic drug etanercept.

Highlights

Biologics have revolutionized the treatment of RA, greatly benefitting the majority of patients receiving them
In the largest replication cohort conducted to date, no evidence for association was observed to support the use of S100A9 as a clinical biomarker predictive of response to the tumour-necrosis factor (TNF)-inhibitor biologic drug etanercept
A recent study has investigated the predictive value of S100A8, S100A9 and S100A8/A9 in pretreatment serum samples collected from RA patients (n = 22), using both mass spectrometry and ELISAs

Summary

Introduction

Biologics have revolutionized the treatment of RA, greatly benefitting the majority of patients receiving them. The S100 protein family could provide one such promising biomarker These multifunctional proteins have been found to be upregulated in inflammatory disorders, including RA [57], levels commonly correlate with clinical markers of disease activity (such as ESR and CRP) [813], and they have been found to be suppressed (both locally at the site of inflammation and distally within the circulatory system) following treatment with biologics [8, 10, 1315]. It is important that replication of the S100A9 association be attempted in independent cohorts in order to confirm the correlation with treatment response. The aim of this research was, to replicate the association with S100A9 in a larger cohort of UK RA patients about to commence treatment with etanercept

Methods

Results

Discussion

Conclusion