Evaluation and treatment of enthesitis-related arthritis

描述（由申请人提供）：该候选人是一名儿科风湿病学初级研究员，接受过临床流行病学方面的高级培训，研究重点是慢性风湿病的药物流行病学和比较有效性，包括膝炎相关关节炎（ERA），这是一种青少年特发性关节炎（JIA）。候选人提出了一个全面的跨学科计划，将为她提供技能和经验，为她发展成为一名独立的儿科风湿病临床研究者。她的职业发展将由一个具有长期富有成效合作历史的综合研究小组指导。该项目将建立在她在MSCE培训和论文工作中获得的药物流行病学和临床流行病学研究知识的基础上，并将为她对所有形式的JIA儿童进行干预研究做好准备。JIA是儿童时期最常见的风湿病，每1000名儿童中有1至4人患病。ERA属于JIA类股，占JIA的10-20%。医生治疗ERA是为了控制炎症和预防诸如慢性葡萄膜炎、生长障碍、挛缩、关节破坏和功能限制等并发症。ERA患儿的一部分会发展为强直性脊柱炎（AS），其特征是脊柱和背部疼痛，僵硬，最终椎体融合。观察性研究表明，不到20%的ERA患儿在诊断后5年内获得缓解。目前，提供和研究ERA治疗的重大挑战受到评估炎症、疾病活动性和治疗反应的方法的限制。提出的研究计划将解决这些挑战，并将(1)评估体检检测炎症的准确性，(2)开发和验证ERA疾病活动指数的复合指标，以及(3)比较ERA事件病例中替代治疗策略的有效性和安全性。本研究将为未来ERA治疗算法的安全性、有效性和成本效益研究提供初步数据、假设和结果测量。

DESCRIPTION (provided by applicant): The candidate is a junior investigator in pediatric rheumatology with advance training in clinical epidemiology and a research focus on pharmacoepidemiology and comparative effectiveness of chronic rheumatic disease, including enthesitis-related arthritis (ERA), which is a category of juvenile idiopathic arthritis (JIA). The candidate proposes a comprehensive interdisciplinary program that will provide her with the skills and experience for her development into an independent clinical investigator in pediatric rheumatology. Her career development will be guided by a comprehensive group of co-investigators with a long history of productive collaboration. The project will build upon the foundations of pharmacoepidemiology and clinical epidemiology research knowledge that she obtained during her MSCE training and thesis work and will prepare her to conduct intervention studies in children with all forms of JIA. JIA is the most common rheumatologic condition in childhood, affecting 1 to 4 per 1,000 children. ERA is a JIA category that accounts for 10-20% of JIA. Physicians treat ERA to control inflammation and to prevent morbidities such as chronic uveitis, growth disturbance, contracture, joint destruction, and functional limitation. A subset of children with ERA will progress to ankylosing spondylitis (AS), a condition characterized by spinal and back pain, stiffness, and eventual fusion of the vertebra. Observational studies suggest that less than 20% of children with ERA achieve remission within five years after diagnosis. Significant challenges to providing and studying ERA treatment today are limited by methods for assessing enthesitis, disease activity, and response to therapy. The proposed plan of research addresses these challenges and will (1) evaluate the accuracy of physical examination to detect enthesitis, (2) develop and validate a composite ERA disease activity index, and (3) compare the effectiveness and safety of alternative treatment strategies in incident cases of ERA. This research will provide the preliminary data, hypotheses, and outcome measures for future safety, efficacy, and cost- effectiveness studies of ERA treatment algorithms.