Musculoskeletal Diseases

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Immune System Diseases

Arthritis

Necrosis

Arthritis, Rheumatoid

Joint Diseases

Rheumatic Diseases

Collagen Diseases

Connective Tissue Diseases

Autoimmune Diseases

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Analgesics

Gastrointestinal Agents

Antiemetics

Neuroprotective Agents

Micronutrients

Hematinics

Vitamins

Methotrexate

Prednisone

Prednisolone

Glucocorticoids

Etanercept

Adalimumab

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Anti-Inflammatory Agents, Non-Steroidal

Infliximab

Leflunomide

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Protective Agents

Tumor Necrosis Factor Inhibitors

Analgesics, Non-Narcotic

Folinic Acid

Folate

Vitamin B9

Infliximab plus Methotrexate , Leflunomide and NSAIDs and Glucocorticoids are permitted but not necessary included.

Etanercept plus Methotrexate , Leflunomide and NSAIDs and Glucocorticoids are permitted but not necessary included.

Adalimumab plus Methotrexate , Leflunomide and NSAIDs and Glucocorticoids are permitted but not necessary included.

Methotrexate will be received orally with dosage of 10mg/ week for every patient and MTX dose must be stable for at least 4 weeks.

methotrexate(necessary)

infliximab :intravenous injection 200mg,every times,0,2,6,14week ,4 times)

infliximab

Etanercept :hypodermic injection,25mg/twice a week

etanercept

Adalimumab:hypodermic injection,40mg/twice a week

adalimumab

LEF will be permitted if patient had received for 1 month before enrollment and will not be changed for 14 weeks.

leflunomide (permitted, not necessary)

NSAIDs will be allowed if patient had received for 1 month before enrollment and will not be changed for 14 weeks.

NSAIDs (permitted,not necessary)

Glucocorticoids (prednisone less than 10mg/day, or equal dosage of other similar drugs) will be permitted if the patient had received for 1 month before enrollment and the dosage will not be changed during the period.

Glucocorticoids (permitted,not necessary)

Fen Li, doctor

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.

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

Screening Protein Predictive of Response to Tumor Necrosis Factor-α Inhibitors Treatment in Chinese Rheumatoid Arthritis From "Real World" and Investigating Its Mechanism Through Signal Pathway

EULAR (European League Against Rheumatism) response is based on changes of DAS28-CRP. The following good, moderate and no response are defined based on changes of DAS28-CRP from baseline to weeks 14: \>1.2 units are good response; 0.6-1.2 units are moderate response; ≤0.6 units are no response.

The DAS28-CRP will be calculated at every visit within the clinical database. The components of the DAS28-CRP score assessment are: Tender/Painful Joint Count (28); Swollen Joint Count (28), hsCRP, and the Subject General Health VAS assessment. This efficacy measurement will be made at baseline and weeks 14.

The TNF level assessment is a direct measurement using ELISA by testing patients' serum. This measurement will be made at baseline and weeks 14.

The classification of EULAR response and the calculation of DAS28-CRP are based on above of Primary Outcome Measure.

Interest proteins will be screened by iTRAQ (isobaric tags for relative and absolute quantitation). This measurement will be made at baseline and weeks 14 by comparing part of patients with good response or no response.

Interest proteins being screened will be verified by Western Blot among all patients of 3 groups.

The classification of EULAR response and the calculation of DAS28-CRP are based on above of Primary Outcome Measure.

SNP of TNF gene will be tested by PCR-RFLP (Polymerase Chain Reaction -Restriction Fragment Length Polymorphism). This measurement will be made at weeks 14 among all 3 groups' patients.

The classification of EULAR response and the calculation of DAS28-CRP are based on above of Primary Outcome Measure.

SNP of gene about interest proteins will tested by PCR-HRM(Polymerase Chain Reaction-high resolution melting). This measurement will be made at weeks 14 among all 3 groups' patients.

Interest proteins are screened and verified on above of Secondary Outcome Measure.

The classification of EULAR response and the calculation of DAS28-CRP are based on above of Primary Outcome Measure.

Fen Li

associate chief physician

Spots Global Cancer Trial Database for tumor necrosis factor α inhibitor