A 7 protein signature for stratifying patients with rheumatoid arthritis for tnfa blocking agent treatment

Rheumatoid arthritis (RA) is a chronic, auto-immune and inflammatory polyarthritis which induces joint damage and disability. Thanks to the better understanding of RA pathophysiology, several anti-cytokines targeted against TNFa, IL-1b, IL-6 or IL-6 receptor and several cellular immunotherapies (anti-CD20 or CTLA-4Ig) have been successfully introduced for RA treatment. Studies have led to the recognition of TNFa as one of the cornerstone cytokines involved in synovial inflammatory process. Such results have provided the basis for the development of TNFa blocking agents (TBAs) for the treatment of RA. Five TNFa blocking agents (TBAs) are currently used for RA treatment, one corresponding to a recombinant soluble form of TNF receptor, TNFRSF1B (etanercept), four others corresponding to an anti-TNFa monoclonal antibody: infliximab, adalimumab (ADA), certolizumab and golimumab. The number of biological agents in RA is continuously increasing and various clinical trials with a TBA / methotrexate combination have shown efficacy in 60-70 % of RA patients. However, clinicians observe that around 30 to 40% of treated patients fail to respond to TBAs. Moreover, TNFa blocking agents may have side effects, they are costly and the efficacy of any given TBA in a given patient is unpredictable. Taking into account the risk of these treatments, the increasing number of available therapeutic molecules in RA, the variability of the response to the various treatment, and to optimize the drug prescription, identification of predictive markers of TBA / methotrexate combination may be highly desirable. Thus, the invention relates to methods and means for predicting rheumatoid arthritis treatment response, using a signature of 7 protein expression in a blood sample. Scientific publication(s): Theranostics, 2015 Aug 9, Obry A. et al., Identification of 7 Proteins in Sera of RA Patients with Potential to Predict ETA/MTX Treatment Response, doi: 10.7150/thno

Keywords: Rheumatoid Arthritis, anti-TNFa treatment, Auto-Immune disease, ELISA, Immunoassay
Patent Application number: EP13 305 778.6
Inventors:
Pascal COSETTEXavier LE LOETOlivier BOYERJulie HARDOUINThierry LEQUERREOlivier VITTECOQAntoine OBRY
Publications:
Theranostics. 2015 Aug 9;5(11):1214-24. doi: 10.7150/thno.12403. eCollection 2015.

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