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. !

项目摘要/摘要 少年特发性关节炎（JIA）是儿童最常见的风湿病，12- 38％的JIA患者患有慢性不对称前葡萄膜炎，通常在4至7之内 关节炎的年份。与JIA相关的葡萄膜炎可能会引起明显的发病率 在所有患者中，有1/3的视力障碍，高达15％的患者在法律上盲目。 抗TNF-α人单克隆抗体Adalimumab已显示出在治疗JIA-的有效性 相关的葡萄膜炎，但与发生严重不良事件的风险有关，包括机会主义 感染和恶性肿瘤。此外，用阿达木单抗长期治疗很昂贵，并且 为患者和医疗保健系统造成大量财务燃烧。但是，停下来 Adalimumab可能会有自己的风险；已经表明，停止和重新启动抗 其他自身免疫性疾病患者的TNF-α治疗与降低有关 对药物的反应。总的来说，这些原因引起了人们对 一旦控制 已经达到了炎症。 我们提出了一个多中心，双掩蔽的随机对照试验来解决临床 有关控制JIA相关性葡萄膜炎患者停止阿达木单抗的相关问题。 在控制JIA相关葡萄膜炎的患者中，我们将比较复发率和时间 比较随机中断阿达木单抗的患者眼部炎症的复发 对于那些继续治疗的人（目标1）。我们还将评估与JIA相关的关键预测指标 葡萄膜炎复发是通过评估临床特征和潜在的生物标志物来复发 葡萄膜炎的复发（AIM 2）。最后，我们将确定停止Adalimumab是否导致总体 在6个月和12个月的访问中，对炎症的控制较少，即使患者在 葡萄膜炎复发（AIM 3）。通过跟随患者从随机化到潜在的缓解和重复 治疗，我们可以更好地了解停止和重新启动Adalimumab的后果。 随着TNF-α抑制剂的越来越多使用，了解停止的风险和好处 控制jia相关葡萄膜炎患者的adalimimab对于临床很重要 练习这些患者。这项研究还可以识别退休的预测指标 和药物反应对于做出证据的治疗决策非常有用。 呢