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脊柱关节炎患者葡萄膜炎治疗的进展——是时候采用生物疗法了吗?

Advances in the treatment of uveitis in patients with spondyloarthritis - is it the time for biologic therapy?

作者信息

Mitulescu Traian-Costin, Trandafir Marius, Dimăncescu Monica-Gabriela, Ciuluvică Radu-Constantin, Popescu Viorela, Predețeanu Denisa, Istrate Sînziana, Voinea Liliana-Mary

机构信息

Department of Ophthalmology, University Emergency Hospital, Bucharest, Romania.

Ophthalmology Department, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.

出版信息

Rom J Ophthalmol. 2018 Apr-Jun;62(2):114-122.

Abstract

Spondyloarthritis (SpA) is a heterogeneous group of diseases that includes ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (ReA), inflammatory bowel disease-associated spondyloarthritis (IBD-SpA), and undifferentiated spondyloarthritis (unSpA). This group of diseases shares several clinical, imaging, and genetic features; the integration of these diseases in the group of SpA is needed for an early diagnosis and a prompt treatment. Uveitis is the most common extra-articular manifestation of SpA. HLA-B27-associated acute anterior uveitis (AAU) is the most frequent form of uveitis encountered in the SpA group. The general prevalence of HLA-B27-associated AAU in the group of SpA is about 30% and the general prevalence of SpA in patients with HLA-B27-associated AAU is over 50%. There are several differences in the clinical picture and evolution of HLA-B27-associated AAU in patients with SpA and knowing this is very important for the best therapeutic decision. Tumor necrosis factor α (TNFα) is a very important mediator not only in the pathogenic mechanisms of SpA, but also in the immune reactions that characterize HLA-B27-associated AAU in SpA. There is much evidence of the role of TNFα in SpA and HLA-B27-associated AAU, multiple studies showing efficacy of anti-TNFα drugs not only on rheumatic manifestations but also on ocular involvement. Conventional therapy of HLA-B27-associated AAU with local or systemic glucocorticoids and immunosuppressive drugs (sulfasalazine, methotrexate, azathioprine, etc.) in order to diminish the ocular inflammation is associated with many side effects, some of them being very severe and even life threatening. Therefore, new treatments, especially biologic therapy with anti-TNFα drugs, open a new opportunity for the treatment of these patients. It is very important to emphasize that antibody anti-TNFα agents (infliximab, adalimumab, golimumab) may be more efficient than soluble receptors of TNFα (etanercept) in decreasing the risk of HLA-B27-associated AAU in patients with SpA. The aim of this review made by a group of ophthalmologists and rheumatologists with recent and fruitful experience regarding the anti-TNF treatment of uveitis in patients with SpA is to make the community of ophthalmologists aware of this biologic therapy and that it is the right time to use it. AU = anterior uveitis; AAU = acute anterior uveitis; AS = ankylosing spondylitis; ASAS = Assessment of SpondyloArthritis Society; DBP = vitamin D binding protein; ESSG = European Spondyloarthropathy Study Group; HLA-B27 = human leukocyte antigen B27; IBD = inflammatory bowel disease; PsA = psoriatic arthritis; ReA = reactive arthritis; SpA = spondyloarthritis; TLRs = Toll-like receptors; TNFα = tumor necrosis factor α; unSpA = undifferentiated spondyloarthritis.

摘要

脊柱关节炎(SpA)是一组异质性疾病,包括强直性脊柱炎(AS)、银屑病关节炎(PsA)、反应性关节炎(ReA)、炎症性肠病相关性脊柱关节炎(IBD-SpA)和未分化脊柱关节炎(unSpA)。这组疾病具有若干临床、影像学和遗传学特征;为了早期诊断和及时治疗,需要将这些疾病归为脊柱关节炎组。葡萄膜炎是脊柱关节炎最常见的关节外表现。HLA-B27相关急性前葡萄膜炎(AAU)是脊柱关节炎组中最常见的葡萄膜炎形式。脊柱关节炎组中HLA-B27相关AAU的总体患病率约为30%,而HLA-B27相关AAU患者中脊柱关节炎的总体患病率超过50%。脊柱关节炎患者中HLA-B27相关AAU的临床表现和病程存在若干差异,了解这一点对于做出最佳治疗决策非常重要。肿瘤坏死因子α(TNFα)不仅是脊柱关节炎发病机制中的重要介质,也是脊柱关节炎中HLA-B27相关AAU特征性免疫反应中的重要介质。有大量证据表明TNFα在脊柱关节炎和HLA-B27相关AAU中发挥作用,多项研究表明抗TNFα药物不仅对风湿性表现有效,对眼部受累也有效。为减轻眼部炎症,采用局部或全身糖皮质激素及免疫抑制药物(柳氮磺胺吡啶、甲氨蝶呤、硫唑嘌呤等)对HLA-B27相关AAU进行传统治疗会带来许多副作用,其中一些副作用非常严重甚至危及生命。因此,新的治疗方法,尤其是抗TNFα药物的生物治疗,为这些患者的治疗带来了新机遇。必须强调的是,抗TNFα抗体药物(英夫利昔单抗、阿达木单抗、戈利木单抗)在降低脊柱关节炎患者发生HLA-B27相关AAU风险方面可能比TNFα可溶性受体(依那西普)更有效。由一组在脊柱关节炎患者葡萄膜炎抗TNF治疗方面有近期丰富经验的眼科医生和风湿病学家撰写本综述的目的是让眼科医生群体了解这种生物治疗方法,并且现在是使用它的恰当时机。AU = 前葡萄膜炎;AAU = 急性前葡萄膜炎;AS = 强直性脊柱炎;ASAS = 脊柱关节炎协会评估;DBP = 维生素D结合蛋白;ESSG = 欧洲脊柱关节病研究组;HLA-B27 = 人类白细胞抗原B27;IBD = 炎症性肠病;PsA = 银屑病关节炎;ReA = 反应性关节炎;SpA = 脊柱关节炎;TLRs = Toll样受体;TNFα = 肿瘤坏死因子α;unSpA = 未分化脊柱关节炎

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