托珠单抗治疗活动性中重度糖皮质激素抵抗性甲状腺眼病：两项独立队列的开放标签前瞻性研究
该开放标签前瞻性研究在波兰华沙和塞尔维亚贝尔格莱德两个中心纳入44例活动性中重度糖皮质激素抵抗性甲状腺眼病患者，给予托珠单抗8 mg/kg静脉注射每4周一次共4个周期并随访24周。华沙队列20/32（62.5%）和贝尔格莱德队列12/12（100%）患者达到主要终点，CAS、突眼、生活质量和TRAb水平均改善，安全性总体可接受。
要点
- 托珠单抗可使糖皮质激素抵抗性甲状腺眼病患者复合眼科评分和生活质量改善。
- CAS降低≥2分在华沙和贝尔格莱德分别为75%和100%。
- 突眼降低≥2 mm在两组分别为59.4%和58.3%，无患者出现TED恶化。
核心结论
- 在糖皮质激素抵抗性活动性中重度甲状腺眼病中，托珠单抗与复合眼科评分、CAS、突眼和生活质量的临床有意义改善相关，安全性总体可接受。
研究设计与样本
- 开放标签前瞻性研究，于2022年5月至2025年5月在波兰华沙和塞尔维亚贝尔格莱德两个三级甲状腺眼病转诊中心开展。
- 共44例成人活动性中重度糖皮质激素抵抗性甲状腺眼病患者接受托珠单抗8 mg/kg静脉注射每4周一次共4个周期，随访24周。
- 主要终点为复合眼科评分改善和疾病特异性生活质量（GO-QoL）改善。
主要发现
- 华沙队列20/32（62.5%）和贝尔格莱德队列12/12（100%）患者达到两个主要终点。
- CAS降低≥2分在华沙为24/32（75%），在贝尔格莱德为12/12（100%）。
- 突眼降低≥2 mm在华沙为19/32（59.4%），在贝尔格莱德为7/12（58.3%）。
- 复视Gorman评分改善≥1级在华沙为7/32（21.9%），在贝尔格莱德为6/12（50%）。
- 睑裂宽度降低≥2 mm在华沙为11/32（34.4%），在贝尔格莱德为8/12（66.7%）。
关键数值与推荐
- TRAb中位数在华沙从7.0降至2.1 IU/L，在贝尔格莱德从4.7降至2.0 IU/L。
- 无患者出现甲状腺眼病恶化。
- 不良事件发生于18/44（40.9%）患者，共47起事件，仅1起为严重不良事件。
临床怎么用
- 托珠单抗可作为糖皮质激素抵抗性活动性中重度甲状腺眼病的有效且安全的二线治疗选择。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
BACKGROUND: Treatment of active, moderate-to-severe thyroid eye disease (TED) remains a challenge. Up to 55% of patients show an incomplete response to intravenous (IV) glucocorticoids (GCs), and relapses are common. Tocilizumab (TCZ), a monoclonal antibody against the interleukin-6 receptor, has been proposed as a second-line therapy for GC-resistant TED. METHODS: We performed an open-label, prospective study at two tertiary TED referral centers (Warsaw, Poland; Belgrade, Serbia) from May 2022 to May 2025. Adults with active, moderate-to-severe, GC-resistant TED received TCZ 8 mg/kg IV every 4 weeks for four cycles and were followed for 24 weeks. Primary endpoints were (1) improvement in the composite ophthalmic score and (2) improvement in disease-specific quality of life (Graves' ophthalmopathy quality of life questionnaire [GO-QoL]). Secondary endpoints included changes in clinical activity score (CAS), proptosis, eyelid aperture, diplopia, thyrotropin receptor antibody (TRAb) levels, and safety. The trial was registered at ClinicalTrials.gov (NCT06367517). RESULTS: A total of 44 patients underwent TCZ treatment (Warsaw, n = 32; Belgrade, n = 12). Both primary endpoints were met by 20/32 (62.5%) patients at Warsaw and all 12/12 (100%) patients at Belgrade. CAS reduction by ≥2 points was observed in 24/32 (75%) and 12/12 (100%) patients, respectively. A reduction of ≥2 mm in proptosis occurred in 19/32 (59.4%) and 7/12 (58.3%). Diplopia improved by ≥1 grade in Gorman score in 7/32 (21.9%) and 6/12 (50%). Eyelid aperture decreased by ≥2 mm in 11/32 (34.4%) and 8/12 (66.7%). Median TRAb levels decreased from 7.0 to 2.1 IU/L (Warsaw) and from 4.7 to 2.0 IU/L (Belgrade). No patients experienced TED deterioration. Adverse events occurred in 18/44 (40.9%) patients (47 events, only 1 severe). CONCLUSIONS: In this prospective, real-world study conducted in two independent cohorts of patients with GC-resistant, active, moderate-to-severe TED, TCZ was associated with clinically meaningful improvements in composite ophthalmic score response, CAS, proptosis, and quality of life, with a generally acceptable safety profile. These findings support TCZ as an effective and safe second-line therapeutic option for GC-resistant TED.
引用
- Rymuza J, Kuś A, Nedeljković Beleslin B, et al. Tocilizumab in Active, Moderate-to-Severe, Glucocorticoid-Resistant Thyroid Eye Disease: An Open-Label Prospective Study in Two Independent Cohorts. Thyroid. 2026. PMID: 42117357. doi:10.1177/10507256261450089
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。