Rituximab for Thyroid Eye Disease
Rituximab for Thyroid Eye Disease
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DOI：
10.1097/iop.0b013e3181c4dfde
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发表时间：
2010-09-01
影响因子：
2
通讯作者：
Lauer, Simeon A.
中科院分区：
文献类型：
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作者：
Silkiss, Rona Z.;Reier, Alice;Lauer, Simeon A.
目的：评价利妥昔单抗介导的b淋巴细胞清除治疗甲状腺眼病（TED）的疗效和安全性。方法：前瞻性、开放标签、干入性临床试验评估12例TED和临床活动评分（CAS） （VISA[视力、炎症、斜视和外观/暴露]分类）在4分或以上的患者，利妥昔单抗（1000 mg）治疗后1年，于第1天和第15天静脉注射。在第二次输注后的基线、4周、8周、12周、24周、36周和52周记录CAS、外周b淋巴细胞水平、甲状腺自身抗体水平和甲状腺功能测试。主要终点是CAS的基线变化。在输注后12个月的观察期内监测促甲状腺免疫球蛋白和促甲状腺激素水平。结果：每次随访时，CAS评分均较基线有统计学显著下降。促甲状腺免疫球蛋白和促甲状腺激素水平与基线相比无统计学显著变化。利妥昔单抗治疗后1个月内观察到b细胞耗竭，输注后36周外周血b淋巴细胞计数开始增加。b细胞耗竭耐受良好，利妥昔单抗输注无不良反应。结论：该组12例患者的CAS评分随着时间的推移显着降低，似乎与利妥昔单抗输注有关。TED多变的自然历史使得它很难明确地分配功效。该结果支持在更大的安慰剂对照试验中继续研究利妥昔单抗治疗TED。
Purpose: To assess the efficacy and safety of rituximab-mediated B-lymphocyte depletion as treatment for thyroid eye disease (TED).Methods: Prospective, open-label, interventional clinical trial evaluating 12 patients with TED and Clinical Activity Scores (CAS) (VISA [vision, inflammation, strabismus and appearance/exposure] classification) of 4 or greater followed for 1 year after rituximab (1000 mg) treatment, administered intravenously on days 1 and 15. CAS, peripheral B-lymphocyte levels, thyroid autoantibody levels, and thyroid function tests were recorded at baseline, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, and 52 weeks after the second infusion. The primary endpoint was a change from baseline in CAS. Thyroid-stimulating immunoglobulin and thyroid-stimulating hormone levels were also monitored over the 12-month postinfusion observation period.Results: CAS scores demonstrated a statistically significant decrease from baseline at each of the follow-up visits. Thyroid-stimulating immunoglobulin and thyroid-stimulating hormone levels demonstrated no statistically significant change from baseline. B-cell depletion was observed within 1 month after rituximab treatment, and peripheral B-lymphocyte counts started to increase 36 weeks after the infusion. B-cell depletion was well tolerated, and there were no adverse effects of the rituximab infusions.Conclusions: CAS scores were significantly reduced over time in this group of 12 patients and appeared to be associated with rituximab infusion. The variable natural history of TED makes it difficult to definitively assign efficacy. The results support the continued investigation of rituximab for TED in a larger placebo-controlled trial.