TUMOR NECROSIS FACTOR-ALPHA INHIBITION (ADALIMUMAB) IN OSTEOARTHRITIS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。假设：用人类肿瘤坏死因子-a单抗(Adalimumab)阻断细胞因子治疗手部炎症性骨关节炎(OA)是安全的，并可以改善其体征和症状。这将是一项针对12名活动期侵蚀性骨性关节炎患者的II期开放式先导研究，每隔一周服用阿达利单抗40毫克，为期12周。在研究登记之前，每个确定的患者都将进行临床评估，包括病史、体检、实验室检查、生命体征(血压、脉搏、呼吸和口腔温度)、PPD皮试和同时服用药物的详细清单。在患者接受研究药物之前，符合纳入/排除标准的实验室测试结果将由医生审查和批准。研究药物将由雅培实验室提供。研究药物将作为注射溶液提供在1毫升预装注射器中，其中包含40毫克阿达利单抗/0.8毫升(50毫克/毫升浓度)。终点：主要终点是在SC每隔一周注射40 mg Adalimumab，持续12周后，在炎症性骨关节炎患者中使用Adalimumab治疗的安全性。为了研究使用Adalimumab的临床疗效，将观察共同的主要终点：第12周的ACR20和第12周的关节严重程度(炎症和压痛)改善。ACR 20的定义是关节压痛和肿胀的数量比基线至少改善20%，以下5个领域中的3个领域至少改善20%：疼痛[基于视觉模拟评分(VAS)]、患者总体评估(PTGA)、医生总体评估(MDGA)、红细胞沉降率和健康评估问卷残疾指数(HAQ-DI)。

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. Hypothesis: Cytokine blockade with a human TNF-a monoclonal antibody (Adalimumab) is safe in the treatment of, and can improve the signs and symptoms of, inflammatory osteoarthritis (OA) of the hands. This will be a Phase II open-label pilot study of 12 patients with active erosive OA receiving Adalimumab 40 mg every other week for twelve weeks. Prior to study enrollment, each patient identified will have a clinical evaluation including medical history, physical examination, laboratory studies, vital signs (blood pressure, pulse, respiration, and oral temperature), PPD skin test, and a detailed list of concurrent medications. Results of laboratory tests required for eligibility will be reviewed and approved by a physician with inclusion/exclusion criteria met before patient receives study drug. Investigational drug will be supplied by Abbott Laboratories. The study drug will be provided as an injection solution in 1-mL pre-filled syringes containing 40 mg Adalimumab/0.8 mL (50 mg/mL concentration). Endpoints: The primary endpoint is the safety of treatment with Adalimumab in subjects with inflammatory OA following SC injections of 40 mg Adalimumab every other week for 12 weeks. To investigate the clinical efficacy of treatment with Adalimumab, co-primary endpoints will be observed: ACR20 at Week 12 and improvement in joint severity (inflammation and tenderness) at Week 12. The ACR 20 is defined by at least a 20% improvement from baseline in the number of tender and swollen joints and at least a 20% improvement in three of the five following domains: pain [based on visual analogue scale (VAS)], patient global assessment (PTGA), physician global assessment (MDGA), erythrocyte sedimentation rate, and Health Assessment Questionnaire disability index (HAQ-DI).