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早期小剂量利妥昔单抗治疗活动性甲状腺眼病:一种有效且耐受性良好的治疗方法。

Early low-dose rituximab for active thyroid eye disease: An effective and well-tolerated treatment.

机构信息

Oxford Eye Hospital, John Radcliffe Hospital, Oxford, UK.

Rheumatology Department, John Radcliffe Hospital, Oxford, UK.

出版信息

Clin Endocrinol (Oxf). 2019 Jul;91(1):179-186. doi: 10.1111/cen.13970. Epub 2019 Apr 11.

DOI:10.1111/cen.13970
PMID:30864162
Abstract

BACKGROUND

Thyroid eye disease (TED) is an autoimmune inflammatory disease that can be disfiguring and potentially sight threatening. Suppression of inflammation in active disease can reduce the risk of visual loss and limit long-term sequelae. Current management involves inflammation suppression using glucocorticoids. The aim of this study was to evaluate the efficacy of early disease intervention with targeted immunomodulatory therapy to alter disease course. This paper reports the efficacy of low-dose rituximab in reducing clinical activity in TED in a small population.

METHODS

A retrospective audit of consecutive patients with active TED managed primarily with a 100 mg rituximab infusion. Further glucocorticoid or steroid-sparing agents were prescribed if clinically indicated. Clinical activity score, VISA overall severity score and Oxford Quality of Life score were recorded at each visit as well as TSH receptor antibody levels (TRAb), B cell subsets and adverse reactions.

RESULTS

Twelve patients had mean follow-up of 6.3 months. Clinical activity scores significantly decreased (mean score 5.08 to 1.58; P < 0.001), VISA overall severity scores reduced by 50% from 12 to 6, P < 0.001 and the mean cumulative dose of IV methylprednisolone was 2.3 g. 100 mg rituximab induced significant CD19 B cell depletion (n = 8, P < 0.001). There was no significant reduction in serum TRAb (n = 8, P = 0.06). A transient infusion-related rash was the only adverse effect, n = 4. QoL scores did not differ markedly before and after treatment.

CONCLUSION

Low-dose rituximab is an efficacious, well-tolerated and safe treatment for active TED; reducing disease activity and allowing reduced administration of systemic steroid.

摘要

背景

甲状腺眼病(TED)是一种自身免疫性炎症性疾病,可能导致容貌受损,并有可能威胁视力。在活动期疾病中抑制炎症可以降低视力丧失的风险,并限制长期后遗症。目前的治疗方法包括使用糖皮质激素抑制炎症。本研究的目的是评估早期疾病干预靶向免疫调节治疗改变疾病进程的疗效。本文报告了小剂量利妥昔单抗在降低 TED 疾病活动度方面的疗效。

方法

对主要采用 100mg 利妥昔单抗输注治疗的活动性 TED 连续患者进行回顾性审核。如果临床上需要,进一步开具糖皮质激素或类固醇保留药物。每次就诊时记录临床活动评分、VISA 总体严重程度评分和牛津生活质量评分,以及 TSH 受体抗体水平(TRAb)、B 细胞亚群和不良反应。

结果

12 例患者的平均随访时间为 6.3 个月。临床活动评分显著降低(平均评分从 5.08 降至 1.58;P<0.001),VISA 总体严重程度评分从 12 分降至 6 分,降低 50%(P<0.001),静脉注射甲基强的松龙的累积剂量为 2.3g。100mg 利妥昔单抗诱导显著的 CD19+B 细胞耗竭(n=8,P<0.001)。血清 TRAb 无显著降低(n=8,P=0.06)。唯一的不良反应是短暂的输注相关皮疹,共 4 例。治疗前后 QoL 评分无明显差异。

结论

低剂量利妥昔单抗治疗活动性 TED 有效、耐受良好且安全;可降低疾病活动度并减少全身类固醇的使用。

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