Department of Neurology and Clinical Neurophysiology, Amsterdam UMC Locatie AMC, University of Amsterdam, Amsterdam, The Netherlands
Department of Epidemiology and Data Science, Amsterdam UMC - Locatie AMC, University of Amsterdam, Amsterdam, The Netherlands.
BMJ Open. 2023 Jul 10;13(7):e067435. doi: 10.1136/bmjopen-2022-067435.
For idiopathic inflammatory myopathies (IIM) ('myositis') standard initial treatment is high-dosed glucocorticoids, which results in relatively slow improvement of muscle strength. Early immunosuppression or modulation by intensive treatment ('hit-early, hit-hard') may induce faster reduction of disease activity and prevent chronic disability due to disease-induced structural muscle damage. Intravenous immunoglobulin (IVIg) in addition to standard glucocorticoid treatment may be promising in this regard as was shown in various studies: add-on IVIg improved symptoms and muscle strength in refractory myositis patients and monotherapy IVIg improved outcomes after 9 weeks, in about half of treatment-naive patients.
We hypothesise that early add-on IVIg leads to a greater clinical response after 12 weeks in patients with newly diagnosed myositis, in comparison to prednisone monotherapy. Second, we expect that early treatment with add-on IVIg leads to a faster time to improvement and sustained positive effects on multiple secondary outcomes.
The Time Is Muscle trial is a phase-2 double-blind placebo-controlled randomised trial. Forty-eight patients with IIM will be treated with IVIg or placebo at baseline (within 1 week after diagnosis) and after 4 and 8 weeks, in addition to standard therapy with prednisone. The primary outcome is the Total Improvement Score (TIS) of the myositis response criteria at 12 weeks. At baseline, and after 4, 8, 12, 26 and 52 weeks, relevant secondary outcomes will be assessed, including time to moderate improvement (TIS≥40), mean daily prednisone dosage, physical activity, health-related quality of life, fatigue and MRI muscle imaging parameters.
Ethical approval was obtained from the medical ethics committee of the Academic Medical Centre, University of Amsterdam, the Netherlands (2020_180; including a first amendment approval at the 12 April 2023; A2020_180_0001). The results will be distributed through conference presentations and peer-reviewed publications.
EU Clinical trials register (2020-001710-37).
对于特发性炎性肌病（IIM）（“肌炎”），标准初始治疗是高剂量糖皮质激素，这导致肌肉力量的改善相对缓慢。早期免疫抑制或强化治疗（“早打、重打”）可能会更快地降低疾病活动度，并防止由于疾病引起的结构性肌肉损伤导致的慢性残疾。静脉注射免疫球蛋白（IVIg）除了标准的糖皮质激素治疗外，在这方面可能很有前途，因为在各种研究中已经表明：IVIg 附加治疗改善了难治性肌炎患者的症状和肌肉力量，单药 IVIg 治疗可改善约一半未经治疗的患者在 9 周后的结局。
我们假设与单独使用泼尼松龙相比，新诊断的肌炎患者在接受早期 IVIg 附加治疗后 12 周的临床反应更大。其次，我们期望早期使用 IVIg 附加治疗能更快地改善病情，并对多个次要结局产生持续的积极影响。
Time Is Muscle 试验是一项 2 期双盲安慰剂对照随机试验。48 例 IIM 患者将在基线时（诊断后 1 周内）接受 IVIg 或安慰剂治疗，并在第 4 周和第 8 周时接受 IVIg 或安慰剂治疗，此外还接受标准的泼尼松龙治疗。主要结局是 12 周时肌炎反应标准的总改善评分（TIS）。在基线时，以及第 4、8、12、26 和 52 周时，将评估相关的次要结局，包括中度改善的时间（TIS≥40）、平均每日泼尼松龙剂量、身体活动、健康相关生活质量、疲劳和 MRI 肌肉成像参数。
荷兰阿姆斯特丹学术医学中心医学伦理委员会已批准该研究（2020_180；包括 2023 年 4 月 12 日的第一次修正案批准；A2020_180_0001）。结果将通过会议报告和同行评议的出版物进行传播。
欧盟临床试验注册处（2020-001710-37）。
