Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease which is characterized by joint inflammation (clinical involvement), by osteo-cartilaginous lesions (structural damage) and generally by bone involvement. All those features lead to great disability. Because it represents a major problem of the public health care system, RA has been selected as one of the main objectives of the government for the next five years.

RA patients who do not respond to DMARDs require a treatment by TNF-a blocking agents. However, no information is available to predict the clinical, structural and bone responses to those new drugs that can be responsible of severe side-effects. Moreover, they are particularly expensive since their yearly cost is estimated between 75000 and 112500 kÏ for the G4 region.

The purpose of the present research project is to determine potential predictive factors of the response to 2 new TNF-a blockers ie adalimumab and etanercept. To address this question, several investigations will be performed including measurement of different blood markers, particularly bone markers, well-defined autoantibodies and new autoantibody populations identified by proteomic analysis, large-scale analysis of gene expression with cDNA arrays from blood mononuclear cells, and use of different imaging tools.

The criteria of judgement will be the clinical, structural and bone responses to those new agents.

This study requires the recruitment of about 200 patients whose one-half will receive adalimumab and the other etanercept for a 1-year period.

At the end of the study, we hope to identify predictive factors of the response to adalimumab and etanercept, which will lead to a better management of those TNF-a blockers. Indeed, they will be prescribed only for the patients who are likely to respond to those drugs. Thus, this study should allow to elaborate theranostic algorithms. Such an approach will have great benefits for the patients: more rapid efficacy, less severe side-reactions and lower costs.

Inclusion Criteria:

• ACR classification criteria of RA
• DAS 28 > 5.1
• inadequately controlled by at least one DMARD
• biologics naïve

Exclusion Criteria:

• exclusion criteria of etanercept,adalimumab and methotrexate (regulation authorities)