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未来已来:用于非感染性儿童前葡萄膜炎的生物制剂

The Future Is Now: Biologics for Non-Infectious Pediatric Anterior Uveitis.

作者信息

Lerman Melissa A, Rabinovich C Egla

机构信息

Division of Rheumatology, The Children's Hospital of Philadelphia (CHOP), Abramson Research Center Suite 1102, 3615 Civic Center Boulevard, Philadelphia, PA, 19104, USA,

出版信息

Paediatr Drugs. 2015 Aug;17(4):283-301. doi: 10.1007/s40272-015-0128-2.

Abstract

Anterior uveitis (AU), inflammation of the iris, choroid or ciliary body, can cause significant eye morbidity, including visual loss. In the pediatric age group, the most common underlying diagnosis for AU is juvenile idiopathic associated uveitis and idiopathic AU, which are the focus of this paper. AU is often resistant to medications such as topical corticosteroids and methotrexate. In the past 15 years, biologic agents (biologics) have transformed treatment. In this review, we discuss those in widespread use and those with more theoretical applications for anterior uveitis. Tumor necrosis factor alpha inhibitors (anti-TNFα) have been available the longest and are used widely to treat pediatric uveitis. The effects of anti-TNFα in children are described mostly in small retrospective case series. Together, the literature suggests that the majority of children treated with anti-TNFα achieve decreased uveitis activity and reduced corticosteroid burden. However, many will have disease flares even on treatment. Only a few small studies directly compare outcomes between alternate anti-TNFα (infliximab and adalimumab). The use of different uveitis grading systems, inclusion criteria, and outcome measures makes cross-study comparisons difficult. Whether the achievement and maintenance of inactive disease occurs more frequently with certain anti-TNFα remains controversial. Newer biologics that modulate the immune system differently (e.g., interfere with Th17 activation through IL-17a and IL-6 blockade, limit T lymphocyte costimulation, and deplete B lymphocytes), have shown promise for uveitis. Studies of these agents are small and include mostly adults. Additional biologics are also being explored to treat uveitis. With their advent, we are hopeful that outcomes will ultimately be improved for children with AU. With many biologics available, much work remains to identify the optimal inflammatory pathway to target in AU.

摘要

前葡萄膜炎(AU)是指虹膜、脉络膜或睫状体的炎症,可导致严重的眼部病变,包括视力丧失。在儿童年龄组中,AU最常见的潜在诊断是青少年特发性相关葡萄膜炎和特发性AU,这也是本文的重点。AU通常对局部用皮质类固醇和甲氨蝶呤等药物耐药。在过去15年中,生物制剂改变了治疗方式。在本综述中,我们讨论了广泛使用的生物制剂以及在前葡萄膜炎中具有更多理论应用的生物制剂。肿瘤坏死因子α抑制剂(抗TNFα)问世时间最长,被广泛用于治疗儿童葡萄膜炎。抗TNFα在儿童中的作用大多在小型回顾性病例系列中有所描述。总体而言,文献表明,大多数接受抗TNFα治疗的儿童葡萄膜炎活动度降低,皮质类固醇负担减轻。然而,许多患儿即使在治疗期间仍会出现疾病复发。只有少数小型研究直接比较了不同抗TNFα(英夫利昔单抗和阿达木单抗)之间的疗效。不同的葡萄膜炎分级系统、纳入标准和疗效指标使得跨研究比较变得困难。使用某些抗TNFα是否更频繁地实现并维持疾病不活动状态仍存在争议。新型生物制剂以不同方式调节免疫系统(例如,通过阻断IL-17a和IL-6来干扰Th17激活、限制T淋巴细胞共刺激以及消耗B淋巴细胞),已显示出对葡萄膜炎的治疗前景。对这些药物的研究规模较小,且大多纳入的是成人。人们也在探索其他生物制剂来治疗葡萄膜炎。随着它们的出现,我们希望最终能改善AU患儿的治疗效果。有多种生物制剂可供选择,要确定AU中最佳的炎症靶点仍有许多工作要做。

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