托珠单抗治疗难治性多发性大动脉炎患者的血管成像：一项随机对照试验的事后分析。
Vascular imaging of patients with refractory Takayasu arteritis treated with tocilizumab: post hoc analysis of a randomized controlled trial.
机构信息
Department of Vascular Physiology, National Cerebral and Cardiovascular Centre Research Institute, Suita.
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
出版信息
Rheumatology (Oxford). 2022 May 30;61(6):2360-2368. doi: 10.1093/rheumatology/keab684.
OBJECTIVES
Tocilizumab, an anti-IL-6 receptor antibody, was investigated in patients with refractory Takayasu arteritis (TAK) in a phase 3 randomized controlled trial. In this post hoc analysis, we investigated whether tocilizumab treatment inhibited the progression of vascular lesions caused by TAK in these patients.
METHODS
Included patients received at least one dose of tocilizumab and underwent CT at baseline and at week 48 after tocilizumab initiation. Three radiologists not involved in the original trial independently evaluated the CT images. Twenty-two arteries from each patient were assessed for change from baseline in wall thickness (primary endpoint), dilatation/aneurysm, stenosis/occlusion or wall enhancement for at least 96 weeks after tocilizumab initiation. Patient-level assessments were also conducted.
RESULTS
In 28 patients, 86.7% of 22 arteries had improved or stable wall thickness at week 96. Proportions of patients with improved or stable, partially progressed or newly progressed lesions were 57.1%, 10.7% and 28.6%, respectively, for wall thickness; proportions with improved or stable lesions were 92.9% for dilatation/aneurysm, and 85.7% for stenosis/occlusion. Patients with newly progressed lesions, reflecting more refractory disease, were prescribed glucocorticoids at dosages that could not be reduced below 0.1 mg/kg/day at week 96.
CONCLUSIONS
Approximately 60% of patients with TAK did not experience progression in wall thickness within 96 weeks after initiation of tocilizumab treatment. Few patients experienced progressed dilatation/aneurysm, or stenosis/occlusion. Wall thickness progression likely resulted from refractory TAK. Patients who experience this should be monitored regularly by imaging, and additional glucocorticoid or immunosuppressive treatment should be considered to avoid vascular progression.
TRIAL REGISTRATION
Japan Pharmaceutical Information Centre number, JapicCTI-142616.
目的
托珠单抗是一种抗白细胞介素 6 受体抗体，在一项 3 期随机对照试验中对难治性大动脉炎（TAK）患者进行了研究。在这项事后分析中，我们研究了托珠单抗治疗是否抑制了这些患者的 TAK 引起的血管病变进展。
方法
纳入的患者至少接受了一剂托珠单抗，并在基线和托珠单抗起始后第 48 周进行 CT 检查。3 名未参与原试验的放射科医生独立评估 CT 图像。从每位患者的 22 条动脉评估从基线开始的管壁厚度变化（主要终点）、扩张/动脉瘤、狭窄/闭塞或壁强化，至少在托珠单抗起始后 96 周进行评估。还进行了患者水平的评估。
结果
在 28 名患者中，86.7%的 22 条动脉在第 96 周时管壁厚度改善或稳定。管壁厚度改善或稳定、部分进展或新进展病变的患者比例分别为 57.1%、10.7%和 28.6%；扩张/动脉瘤的改善或稳定比例为 92.9%，狭窄/闭塞的比例为 85.7%。新进展病变的患者反映出疾病更具难治性，在第 96 周时给予的糖皮质激素剂量不能减少至低于 0.1mg/kg/天。
结论
约 60%的 TAK 患者在托珠单抗治疗起始后 96 周内，管壁厚度无进展。少数患者出现进展性扩张/动脉瘤或狭窄/闭塞。管壁厚度进展可能是由于难治性 TAK 所致。有此进展的患者应定期通过影像学进行监测，并应考虑额外的糖皮质激素或免疫抑制治疗，以避免血管进展。
临床试验注册
日本医药信息中心编号，JapicCTI-142616。
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