Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Marqués de Valdecilla (IDIVAL), and University of Cantabria, Santander, Spain.
Hospital Universitario La Fe, Valencia, Spain.
Arthritis Rheumatol. 2017 Mar;69(3):668-675. doi: 10.1002/art.39940.
To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)-associated uveitis.
We conducted a multicenter study of patients with JIA-associated uveitis that was refractory to conventional immunosuppressive drugs and anti-tumor necrosis factor (anti-TNF) agents.
We assessed 25 patients (21 female; 47 affected eyes) with a mean ± SD age of 18.5 ± 8.3 years. Uveitis was bilateral in 22 patients. Cystoid macular edema was present in 9 patients. Ocular sequelae found at initiation of TCZ included cataracts (n = 13), glaucoma (n = 7), synechiae (n = 10), band keratopathy (n = 12), maculopathy (n = 9), and amblyopia (n = 5). Before TCZ, patients had received corticosteroids, conventional immunosuppressive drugs, and biologic agents (median 2 [range 1-5]), including adalimumab (n = 24), etanercept (n = 8), infliximab (n = 7), abatacept (n = 6), rituximab (n = 2), anakinra (n = 1), and golimumab (n = 1). Patients received 8 mg/kg TCZ intravenously every 4 weeks in most cases. TCZ yielded rapid and maintained improvement in all ocular parameters. After 6 months of therapy, 79.2% of patients showed improvement in anterior chamber cell numbers, and 88.2% showed improvement after 1 year. Central macular thickness measured by optical coherence tomography in patients with cystoid macular edema decreased from a mean ± SD of 401.7 ± 86.8 μm to 259.1 ± 39.5 μm after 6 months of TCZ (P = 0.012). The best-corrected visual acuity increased from 0.56 ± 0.35 to 0.64 ± 0.32 (P < 0.01). After a median follow-up of 12 months, visual improvement persisted, and complete remission of uveitis was observed in 19 of 25 patients. Significant reduction in the prednisone dosage was also achieved. The main adverse effects were severe autoimmune thrombocytopenia in 1 patient, pneumonia and then autoimmune anemia and thrombocytopenia in 1 patient, and viral conjunctivitis and bullous impetigo in 1 patient.
TCZ appears to be a useful therapy for severe refractory JIA-associated uveitis.
评估托珠单抗（TCZ）治疗幼年特发性关节炎（JIA）相关性葡萄膜炎的疗效。
我们进行了一项多中心研究，纳入了对常规免疫抑制剂和抗肿瘤坏死因子（anti-TNF）药物治疗无效的 JIA 相关性葡萄膜炎患者。
我们评估了 25 例（21 例女性；47 只受累眼）平均年龄为 18.5±8.3 岁的患者。22 例患者的葡萄膜炎为双侧性。9 例患者存在黄斑囊样水肿。在开始 TCZ 治疗时发现的眼部后遗症包括白内障（n=13）、青光眼（n=7）、虹膜后粘连（n=10）、带状角膜病变（n=12）、黄斑病变（n=9）和弱视（n=5）。在 TCZ 治疗前，患者已接受皮质类固醇、常规免疫抑制剂和生物制剂（中位数 2[范围 1-5]种）治疗，包括阿达木单抗（n=24）、依那西普（n=8）、英夫利昔单抗（n=7）、阿巴西普（n=6）、利妥昔单抗（n=2）、阿那白滞素（n=1）和戈利木单抗（n=1）。大多数情况下，患者接受 8mg/kg TCZ 静脉注射，每 4 周 1 次。TCZ 使所有眼部参数迅速且持续改善。经过 6 个月的治疗，79.2%的患者前房细胞计数改善，1 年后 88.2%的患者改善。接受 TCZ 治疗 6 个月后，光学相干断层扫描测量的黄斑囊样水肿中央视网膜厚度从平均（±SD）401.7±86.8μm 降至 259.1±39.5μm（P=0.012）。最佳矫正视力从 0.56±0.35 增加到 0.64±0.32（P<0.01）。中位随访 12 个月后，视力持续改善，25 例患者中有 19 例完全缓解。皮质类固醇剂量也显著减少。主要不良反应为 1 例患者出现严重自身免疫性血小板减少症，1 例患者出现肺炎，随后出现自身免疫性贫血和血小板减少症，1 例患者出现病毒性结膜炎和脓疱疮。
TCZ 似乎是治疗严重难治性 JIA 相关性葡萄膜炎的一种有效治疗方法。
