Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial

阿达木单抗在幼年特发性关节炎相关葡萄膜炎中的停止试验

• 批准号: 10405427
• 负责人: NISHA ACHARYA
• 金额: $ 122.83万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10405427
• 关键词: 16 year old; Address; Adverse event; Age; Anterior uveitis; Antibodies; Arthritis; Autoimmune Diseases; Benefits and Risks; Biological; Biological Markers; Biological Products; Biological Response Modifier Therapy; C-reactive protein; Cataract; Characteristics; Child; Childhood; Chronic; Chronic Childhood Arthritis; Clinical; Data; Decision Making; Disease; Disease remission; Disease-Modifying Second-Line Drugs; Erythrocyte Sedimentation Rate; Etiology; Evidence based treatment; Financial Hardship; Flare; Glaucoma; Healthcare Systems; Immunosuppressive Agents; Inflammation; Inflammatory; Keratopathy; Lead; Malignant Neoplasms; Masks; Methotrexate; Morbidity - disease rate; Ophthalmologist; Opportunistic Infections; Outcome; Pathology; Patients; Persons; Pharmaceutical Preparations; Practice Management; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Recurrence; Refractory; Relapse; Retreatment; Risk; Rogaine; S100A8 gene; Safety; Secondary to; Serious Adverse Event; Serum; TNF gene; Time; Treatment Failure; Uveitis; Visit; Visual impairment; Withdrawal; Withdrawing Treatments; adalimumab; adverse event risk; clinical practice; clinically relevant; disorder control; drug withdrawal; efficacy evaluation; evidence based guidelines; human monoclonal antibodies; inhibitor; interest; legally blind; macula; potential biomarker; relapse prediction; response; rheumatologist; treatment arm; treatment duration; tumor necrosis factor-alpha inhibitor

PROJECT SUMMARY/ABSTRACT Juvenile idiopathic arthritis (JIA) is the most common rheumatologic condition in children, and 12- 38% of patients with JIA develop chronic asymptomatic anterior uveitis, typically within 4 to 7 years of arthritis onset. JIA-associated uveitis can cause significant morbidity, with as many as 1/3 of all patients developing substantial visual impairment and up to 15% becoming legally blind. The anti-TNF-α human monoclonal antibody adalimumab has shown efficacy in treating JIA- associated uveitis, but is associated with a risk of serious adverse events, including opportunistic infections and malignancy. Furthermore, long-term treatment with adalimumab is expensive and causes significant financial burden for the patient and healthcare system. However, stopping adalimumab may come with risks of its own; it has been shown that stopping and restarting anti- TNF-α therapy in patients with other autoimmune diseases is associated with reduced responsiveness to the drug. Collectively, these reasons contribute to a growing interest in developing evidence-based guidelines for stopping adalimumab treatment once control of inflammation has been achieved. We propose a multicenter, double-masked, randomized controlled trial to address clinically relevant questions about stopping adalimumab in patients with controlled JIA-associated uveitis. In patients with controlled JIA-associated uveitis, we will compare rate of recurrence and time to recurrence of ocular inflammation in patients randomized to discontinue adalimumab compared to those who continue treatment (Aim 1). We will also evaluate key predictors of JIA-associated uveitis recurrence by assessing clinical characteristics and potential biomarkers associated with recurrence of uveitis (Aim 2). Finally, we will determine if stopping adalimumab leads to overall less control of inflammation at the 6 and 12-month visits, even if patients restart adalimumab after a uveitis recurrence (Aim 3). By following patients from randomization to potential relapse and re- treatment, we can better understand the consequences of stopping and restarting adalimumab. With the increasing use of TNF-α inhibitors, understanding the risks and benefits of stopping adalimumab in patients with controlled JIA-associated uveitis is important to inform clinical practice for management of these patients. This study could also identify predictors of relapse and drug response that would be useful in making evidence-based treatment decisions. !

项目概要/摘要 幼年特发性关节炎 (JIA) 是儿童中最常见的风湿病，12- 38% 的 JIA 患者会出现慢性无症状前葡萄膜炎，通常在 4 至 7 年内出现 关节炎发病多年。 JIA 相关葡萄膜炎可导致严重的发病率，其中多达 1/3 的患者出现严重视力障碍，多达 15% 的患者成为法定盲人。 抗 TNF-α 人单克隆抗体阿达木单抗已显示出治疗 JIA 的功效 相关葡萄膜炎，但与严重不良事件的风险相关，包括机会性 感染和恶性肿瘤。此外，阿达木单抗的长期治疗费用昂贵且 给患者和医疗保健系统造成沉重的经济负担。然而，停止 阿达木单抗可能存在其自身的风险；已经表明，停止和重新启动反 患有其他自身免疫性疾病的患者接受 TNF-α 治疗可降低 对药物的反应。总的来说，这些原因促使人们对 制定基于证据的指南，一旦控制住就停止阿达木单抗治疗 炎症已经达到了。 我们提出了一项多中心、双盲、随机对照试验来解决临床问题 关于在 JIA 相关葡萄膜炎得到控制的患者中停止使用阿达木单抗的相关问题。 在 JIA 相关葡萄膜炎得到控制的患者中，我们将比较复发率和治疗时间 随机停止使用阿达木单抗的患者中眼部炎症复发的比较 那些继续治疗的人（目标 1）。我们还将评估 JIA 相关的关键预测因素 通过评估与葡萄膜炎相关的临床特征和潜在生物标志物来评估葡萄膜炎复发 葡萄膜炎复发（目标 2）。最后，我们将确定停止阿达木单抗是否会导致总体 即使患者在 6 个月和 12 个月就诊后重新开始使用阿达木单抗，炎症控制也较差 葡萄膜炎复发（目标 3）。通过跟踪患者从随机分组到潜在复发和再复发 治疗中，我们可以更好地了解停止和重新开始阿达木单抗的后果。 随着 TNF-α 抑制剂的使用越来越多，了解停止使用的风险和益处 阿达木单抗在控制性 JIA 相关葡萄膜炎患者中的应用对于临床指导非常重要 管理这些患者的实践。这项研究还可以确定复发的预测因素 以及有助于做出基于证据的治疗决策的药物反应。 ！