BIOLOGY IN RESPONSE TO TNF BLOCKADE IN JIA

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. BACKGROUND. 35% of children with Polyarticular Juvenile Rheumatoid Arthritis (P-JRA) treated with anti-TNF monoclonal antibody therapy (infliximab or adalimumab) demonstrate clinically inactive disease (CID). The proper time to stop anti-TNF monoclonal antibody therapy in a child demonstrating CID is unknown. These therapies can be associatied with short-and medium- term side effects in children with JRA. Long term effects in both adults and children are unknown. SPECIFIC AIMS. 1. Perform a pharmacokinetic (PK) study in P-JRA on either infliximab or adalimumab to determine proper sampling time for an in vivo cytokine capture assay (IVCCA) that quantitates in vivo TNF production. 2. Perform cross sectional study in P-JRA to determine ability of the IVCCA to distinguish between levels of in vitro production of TNF. METHODS.. Timed PK sampling in 6 children with P-JRA on infliximab and 6 on adalimumab will determine the most informative time point for sampling for the IVCCA. A cross sectional study in 3 P-JRA groups on infliximab or adalimumab will be performed (active disease, partial response and inactive arthritis). SIGNIFICANCE. This is first human study of a novel biomarker of in vivo TNF production. If effective, it could lead to safer and more cost effective use of infliximab and adalimumab in a variety of diseases in adults and children.