07.02 Genetic signatures in rheumatoid arthritis: changes upon anti-tnf therapy and association with response to biological treatment

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Abstract

Background

Genetic signatures may be involved in the pathogenesis of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). In addition, such genetic patterns may change overtime upon treatment with anti-TNF biologics. With respect to pharmacogenomics, pre-treatment genomics may predict response or non-response to biological therapy.

Objectives

In the present study, we wished to determine gene expression changes due to anti-TNF therapy. Furthermore, we wished to study associations between baseline genetic signature and response to TNF blockade.

Patients and methods

Altogether 23 RA and 17 AS patients were recruited for the study. Among RA patients, 10 received certolizumab pegol (CZP), and 13 etanercept (ETN). All AS patients were treated with ETN. Gene expression analysis using Affymetrix microarray and PrimeView array was performed at baseline and after 2 weeks of treatment. EULAR response criteria were used to differentiate responders (R) from non-responders (NR) after 12 weeks of treatment using GeneSpring software. Principal Component Analysis (PCA) was also performed. Changes in gene expression patterns were also determined between baseline and 2 weeks.

Results

In the CZP-treated RA group, 4 patients were R and 6 were NR. Altogether 453 genes showed significantly differential expression between N and NR. In the RA-ETN group, 10 patients were R, and 3 were NR. Here, 836 genes exerted differential expression. When a CZP- and ETN-treated patients, were pooled, 165 genes separated R from NR. In the AS population, 14 patients were R and 3 were NR. 177 genes differentiated between R and NR. When changes in gene expression patterns from baseline to week 2 were determined, in the RA-CZP, RA-ETN, RA-all and AS groups 370, 79, 24 and 76 genes showed significant changes in expression.

Conclusions

Using microarray, genetic signatures may differentiate RA patients responding or not responding to anti-TNF therapy. Furthermore, a large set of genes show differential expression before versus 2 weeks after biologic treatment.

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