Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial

项目摘要/摘要 幼年特发性关节炎(JIA)是儿童最常见的风湿病，12- 38%的JIA患者发展为慢性无症状前葡萄膜炎，通常在4至7岁之间 多年的关节炎发作。与贾氏相关的葡萄膜炎可导致显著的发病率，多达 三分之一的患者出现严重的视力障碍，高达15%的患者在法律上失明。 抗肿瘤坏死因子-α人源单抗阿达利姆单抗治疗日本血吸虫病疗效显著 相关性葡萄膜炎，但与严重不良事件的风险有关，包括机会性 感染和恶性。此外，阿达利玛单抗的长期治疗费用昂贵， 给患者和医疗保健系统带来了巨大的经济负担。然而，停止 阿达利单抗可能有其自身的风险；已有研究表明，停止和重新启动抗- 其他自身免疫性疾病患者的肿瘤坏死因子-α治疗与减少有关 对药物的反应。总而言之，这些原因促进了人们对 制定循证指南，一旦控制了阿达利玛单抗治疗 炎症已经实现。 我们提出了一项多中心、双掩蔽、随机对照试验，以解决临床 控制的JIA相关性葡萄膜炎患者停用阿达利单抗的相关问题。 在受控的JIA相关性葡萄膜炎患者中，我们将比较复发率和达到 随机停用阿达利单抗的患者眼部炎症复发的比较 对于那些继续治疗的人(目标1)。我们还将评估与JIA相关的关键预测因素 评估葡萄膜炎复发的临床特征和潜在的生物标志物 葡萄膜炎复发(目标2)。最后，我们将确定停用阿达利单抗是否会导致总体 在6个月和12个月的访问中炎症控制较差，即使患者在6个月和12个月后重新启动adalimumab 葡萄膜炎复发(目标3)。通过跟踪患者从随机到潜在的复发和再... 治疗后，我们可以更好地了解停止和重新启动阿达利单抗的后果。 随着肿瘤坏死因子-α抑制剂的使用越来越多，了解停药的风险和好处 在受控的JIA相关性葡萄膜炎患者中应用阿达单抗对临床具有重要意义 这些病人的管理实践。这项研究还可以确定复发的预测因素 和药物反应，这将有助于做出循证治疗决定。 好了！

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. !