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Pretreatment synovial transcriptional pro le is associated with early and late clinical response in rheumatoid arthritis patients treated with rituximab

Lookup NU author(s): Dr Vanessa Hogan, Professor Jaap Van Laar

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Abstract

Objective Personalised healthcare is contingent on the identification of biomarkers that represent disease relevant pathways and predict drug response. The authors aimed to develop a gene expression signature in synovial tissue that could enrich clinical response of rheumatoid arthritis (RA) patients to rituximab. Methods The authors studied synovial gene expression using high-throughput quantitative real-time-PCR in 20 RA patients who underwent arthroscopy before and after treatment with rituximab. Several objective approaches were used to explore patterns in the data and to find genes associated with changes in disease activity due to treatment. Results This analysis revealed two patient populations associated with distinct clinical, laboratory and histological features and, importantly, showed enrichment for response (60% non-responders vs 90% responders). A composite baseline gene score (GS) correlated with change in disease activity score (Delta DAS) between baseline and month 3 (r=0.74, p=0.0002), but also with Delta DAS at later time-points (month 9, r=0.54, p=0.016; month 15, r=0.45, p=0.06; month 21, r=0.72, p=0.003). Notably, the GS significantly correlated with baseline erythrocyte sedimentation rate (r=0.69, p=0.0008), but not with other DAS components. The GS genes represented T cell, macrophage, remodelling and interferon-a biology. Responders demonstrated higher expression of macrophage and T cell genes, while non-responders showed higher expression of interferon-alpha and remodelling genes. Conclusions This study reveals a baseline synovial GS that correlates with early and late clinical responses to rituximab. The GS biology suggests that T cells and macrophages are important for response to B cell depleting therapy, while expression of remodelling and interferon-alpha genes correlates with poor response.


Publication metadata

Author(s): Hogan VE, Holweg CTJ, Choy DF, Kummerfeld SK, Hackney JA, Onno Teng YK, Townsend MJ, van Laar JM

Publication type: Article

Publication status: Published

Journal: Annals of the Rheumatic Diseases

Year: 2012

Volume: 71

Issue: 11

Pages: 1888-1894

Print publication date: 26/06/2012

ISSN (print): 0003-4967

ISSN (electronic):

Publisher: BMJ Group

URL: http://dx.doi.org/10.1136/annrheumdis-2011-201115

DOI: 10.1136/annrheumdis-2011-201115


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