Department of Medicine, Division of Rheumatology, George Washington University School of Medicine and Health Sciences, Washington DC.
Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington DC.
Arthritis Rheumatol. 2023 Jul;75(7):1229-1237. doi: 10.1002/art.42450. Epub 2023 Jun 7.
This open-label, 24-week study was conducted to evaluate the safety and efficacy of abatacept in patients with refractory juvenile dermatomyositis (DM).
Ten patients ≥7 years of age with moderate disease activity were enrolled in a 24-week study to examine the safety of subcutaneous abatacept and patient responses to the treatment. The primary endpoint was the International Myositis Assessment and Clinical Studies (IMACS) group Definition Of Improvement (DOI). Secondary endpoints included safety, changes in the core set activity measures (CSMs) of the IMACS group and the Pediatric Rheumatology International Trials Organization, and improvements in disease activity based on the American College of Rheumatology (ACR)/EULAR response criteria for juvenile DM. Radiologists blinded with regard to participant data assessed magnetic resonance images (MRIs) of patient thigh muscles. Interferon (IFN)-regulated gene score was performed on whole-blood RNA samples using a NanoString assay, and cytokines were assessed using a Luminex assay.
Five patients achieved DOI at week 12, and 9 patients achieved DOI at week 24, including 2 patients with minimal, 4 patients with moderate, and 3 patients with major improvement by the 2016 ACR/EULAR response criteria for juvenile DM when patients were assessed using the CSMs of the IMACS Group. Improvements from baseline were seen in all CSMs at weeks 12 and 24, except in muscle enzymes. Daily glucocorticoid doses decreased from a mean of 16.7 mg at baseline to 10.2 mg at week 24 (P = 0.002). Average MRI muscle edema scores decreased from a mean baseline score of 5.3 to 2.3 at week 24 (P = 0.01). Six patients had down-trending IFN-regulated gene scores and galectin-9 expression at week 24. Decreases in IFN-regulated gene scores and in levels of interferon-γ-inducible protein 10kDa, galectin-9, and interleukin-2 correlated with improvements in disease activity and in muscle edema shown on MRI. Eleven grade 2 or 3 treatment-emergent adverse events were observed.
This open-label study demonstrated that abatacept may be beneficial for patients with treatment-refractory juvenile DM.
本开放性、24 周研究旨在评估阿巴西普治疗难治性幼年特发性皮肌炎（DM）患者的安全性和疗效。
10 名年龄≥7 岁、疾病活动度中度的患者参与了 24 周研究，以检查皮下阿巴西普的安全性和患者对治疗的反应。主要终点是国际肌炎评估和临床研究（IMACS）组的定义改善（DOI）。次要终点包括安全性、IMACS 组和儿科风湿病国际试验组织的核心活动测量（CSM）的变化，以及根据美国风湿病学会（ACR）/幼年特发性皮肌炎欧洲联盟研究组（EULAR）反应标准评估的疾病活动改善。对患者大腿肌肉进行磁共振成像（MRI）评估的放射科医生对患者数据进行盲法评估。使用 NanoString 分析对全血 RNA 样本进行干扰素（IFN）调节基因评分，并使用 Luminex 分析评估细胞因子。
5 名患者在第 12 周时达到 DOI，9 名患者在第 24 周时达到 DOI，包括 2 名患者根据 2016 年 ACR/EULAR 反应标准评估为幼年特发性皮肌炎的患者时，达到最小、中度和重度改善的患者各有 4 名和 3 名。在第 12 周和第 24 周，除肌肉酶外，所有 CSM 均见从基线改善。从基线时的平均 16.7mg 每日糖皮质激素剂量降至第 24 周时的 10.2mg（P=0.002）。平均 MRI 肌肉水肿评分从基线时的 5.3 分降至第 24 周时的 2.3 分（P=0.01）。6 名患者在第 24 周时出现 IFN 调节基因评分和半乳糖凝集素-9 表达下降趋势。IFN 调节基因评分下降以及干扰素-γ诱导蛋白 10kDa、半乳糖凝集素-9 和白细胞介素-2 水平降低与 MRI 上显示的疾病活动改善和肌肉水肿减少相关。观察到 11 例 2 级或 3 级治疗后出现的不良事件。
本开放性研究表明，阿巴西普可能对治疗难治性幼年特发性皮肌炎患者有益。
