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: 10155488
• 负责人: NISHA ACHARYA
• 金额: $ 120.34万
• 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/10155488
• 关键词: 16 year old; Address; Adverse event; Age; Anterior uveitis; Antibodies; Arthritis; Autoimmune Diseases; Benefits and Risks; Biological; Biological Markers; 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/antagonist; 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. !

项目总结/摘要 幼年特发性关节炎（JIA）是儿童中最常见的风湿性疾病， 38%的JIA患者发生慢性无症状前葡萄膜炎，通常在4 - 7岁之间。 关节炎发作的时间JIA相关的葡萄膜炎可引起显著的发病率， 1/3的患者出现严重的视力障碍，高达15%的患者成为法定失明。 抗TNF-α人源单克隆抗体阿达木单抗已显示出治疗JIA的有效性， 相关的葡萄膜炎，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， 给患者和医疗保健系统造成巨大的经济负担。可是时停 阿达木单抗可能有其自身的风险;已经证明，停止和重新开始抗- 其他自身免疫性疾病患者的TNF-α治疗与降低 对药物的反应。总的来说，这些原因导致人们对以下方面越来越感兴趣： 制定循证指南，一旦控制了 已经实现了炎症。 我们建议进行一项多中心、双盲、随机对照试验， 关于在JIA相关葡萄膜炎控制患者中停用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， 随机分配至阿达木单抗停药的患者中眼部炎症复发率， 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复发相关的临床特征和潜在生物标志物 葡萄膜炎复发（目的2）。最后，我们将确定停用阿达木单抗是否会导致总体 6个月和12个月访视时炎症控制较差，即使患者在治疗后重新开始阿达木单抗治疗， 葡萄膜炎复发（目标3）。通过随访患者从随机化到潜在复发和再发， 治疗，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，了解停用TNF-α抑制剂的风险和益处 阿达木单抗在控制JIA相关葡萄膜炎患者中的应用对于告知临床 管理这些病人的方法。这项研究还可以确定复发的预测因素 和药物反应，这将有助于制定循证治疗决策。 !