Predictability Studies on the Efficacy of TNF-α Inhibitors in Chinese RA From "Real World"

Rheumatoid arthritis (RA) is a chronic and disabling disease. tumor necrosis factor-a(TNF-a) inhibitors have demonstrated an outstanding performance in relieving joint inflammation and retarding bone erosion involved in RA. However, there is still about one-thirds of RA patients had a poor response to TNF α inhibitors. The Investigators hope to discover prediction protein with a domestic genetic background and finally establish prediction system with Chinese characteristics.

Rheumatoid arthritis (RA) is a chronic and disabling disease. TNF-α inhibitors have demonstrated an outstanding performance in relieving joint inflammation and retarding bone erosion involved in RA. However, there is still about one-thirds of RA patients had a poor response to TNF α inhibitors. Currently the personalized biological treatment is the research hotspot. Recent studies focuses on exploring biomarkers predictive of drug response. The research methods such as genomics, transcriptomics, proteomics, metabolomics and immunocytology, have been applied,but they are not successfully integrated. The related studies in China are still at an initial stage, which necessitates an in-depth study in this area. The investigators' preliminary study showed that TNF-α-308 gene polymorphisms existed in Chinese RA patients and phosphoinositide 3-kinase/Akt signal pathway was activated in proliferated synovial fibroblasts stimulated by TNF-α. Therefore, for the first attempt in China, the investigators intend to screen for differential proteins by using isobaric tags for relative and absolute quantitation(iTRAQ) technique in RA patients receiving anti-TNF-α therapy, and then verify the predictive effects of selected differential proteins from the upstream gene polymorphism to the downstream protein expression. The investigators will also explore the mechanisms of differential proteins involved in TNF-α related signal pathway by using in vitro gene transfer, siRNA interference, and RA animal models. Through this study investigator hope to discover some prediction proteins with a domestic genetic background and finally establish a prediction system with Chinese characteristics.

Eligibility Criteria:
Inclusion Criteria:

* signed the consents voluntarily
* age between 18-75 years old
* patients were meet the American College of Rheumatology(ACR)

  * European League Against Rheumatism(EULAR) 2009 diagnostic criteria (total scores beyond 6)
* for severe RA patients DAS28-CRP≥5.1
* The participants receiving Infliximab plus Methotrexate will be invited to enroll the study.
* The participants receiving Etanercept plus Methotrexate will be invited to enroll the study.
* The participants receiving Adalimumab plus Methotrexate will be invited to enroll the study.

Exclusion Criteria:

* The patient have the disease history or the disease of cardiovascular, respiratory system, liver, gastrointestinal tract, endocrine, hematology, neurology or psychiatric disturbance, and investigator believe that there are some risks for patients with these disease history or disease when use study drugs, or these disease history or disease will disturb the interpret of data
* Patients with cancer in situ or exist the possibility of cancer malignancies
* Basically or completely loss of mobility, lack self-care ability, such as rely on a wheelchair or bed-ridden .
* Experimental examination display any of the following:

Aspartate aminotransferase or alanine aminotransferase\>1.5 times of the upper limit of the normal value Total bilirubin\>1.5 times of the upper limit of the normal value Total white blood cells \<2500 cells/L absolute neutrophil count \<1200 cells/L lymphocyte count \<750 cells/L platelet\<100000/L

* Patients with symptomatic herpes simplex
* Latent tuberculosis signal (PPD+++ OR T-SPOT\>5 )
* Positive result of the hepatitis B virus (HBV):

HBsAg + Or HBeAg + Or HBeAg + Or HBcAb + Or HBV DNA +

* hepatitis C virus(HCV)+ or HCV RNA +
* HIV infection or HIV+
* 1 months before join the group, from a clinical point of view,patients have a serious infection caused by the virus, bacteria, fungi, or parasites
* Pregnancy 、 location 、prepare for conceive in one years or there is risk to impregnate their partners
* Patients received any biological therapies for 6 months, or participated any other clinical trials of new drugs
* A history of drug allergy
* A history of heavy drink
* vaccinate the live vaccine recently