NCT02878161

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

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 240 (estimated)
• Sponsor: Fen Li · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Rheumatoid Arthritis

Interventions

Type	Name	Description
DRUG	methotrexate(necessary)	Methotrexate will be received orally with dosage of 10mg/ week for every patient and MTX dose must be stable for at least 4 weeks.
BIOLOGICAL	infliximab	infliximab :intravenous injection 200mg,every times,0,2,6,14week ,4 times)
BIOLOGICAL	etanercept	Etanercept :hypodermic injection,25mg/twice a week
BIOLOGICAL	adalimumab	Adalimumab:hypodermic injection,40mg/twice a week
DRUG	leflunomide (permitted, not necessary)	LEF will be permitted if patient had received for 1 month before enrollment and will not be changed for 14 weeks.
DRUG	NSAIDs (permitted,not necessary)	NSAIDs will be allowed if patient had received for 1 month before enrollment and will not be changed for 14 weeks.
DRUG	Glucocorticoids (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.

Timeline

• Start date: 2016-01-01
• Primary completion: 2019-12-01
• Completion: 2019-12-01
• First posted: 2016-08-25
• Last updated: 2016-08-25