BIOLOGY IN RESPONSE TO TNF BLOCKADE IN JIA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 背景35%接受抗TNF单克隆抗体治疗（英夫利昔单抗或阿达木单抗）的多关节幼年型风湿性关节炎（P-JRA）儿童表现出临床非活动性疾病（CID）。对于显示CID的儿童，停止抗TNF单克隆抗体治疗的适当时间尚不清楚。这些治疗可能与JRA儿童的短期和中期副作用有关。对成人和儿童的长期影响尚不清楚。 具体目标。 1.在P-JRA中对英夫利西单抗或阿达木单抗进行药代动力学（PK）研究，以确定定量体内TNF产生的体内细胞因子捕获试验（IVCCA）的适当采样时间。 2.在P-JRA中进行横断面研究，以确定IVCCA区分TNF体外产生水平的能力。 METHODS.. 6例接受英夫利西单抗治疗的P-JRA儿童和6例接受阿达木单抗治疗的P-JRA儿童的定时PK采样将确定IVCCA采样的最具信息性的时间点。将在3个P-JRA组中进行英夫利西单抗或阿达木单抗的横断面研究（活动性疾病、部分缓解和非活动性关节炎）。 意义这是第一次对体内TNF产生的新型生物标志物进行人体研究。如果有效的话，它可能会导致在成人和儿童的各种疾病中使用英夫利西单抗和阿达木单抗更安全，更具成本效益。

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.