University of Pittsburgh School of Medicine, Pittsburgh, PA.
University of California, Los Angeles, CA.
Medicine (Baltimore). 2021 Jan 8;100(1):e23677. doi: 10.1097/MD.0000000000023677.
Dermatomyositis (DM) is an inflammatory myopathy characterized by distinct skin manifestations and muscle weakness. Intravenous immunoglobulin (IVIg) has been used off-label as adjuvant therapy in DM, but is not indicated for DM, due to lack of proven efficacy in a large randomized controlled trial. The objective of the ProDERM (Progress in DERMatomyositis) study was to evaluate the efficacy, safety and long-term tolerability of IVIg (Octagam 10%) in patients with DM in a randomized, placebo-controlled, double-blind, Phase III study.
Adult patients with active DM who were continuing standard therapy at a stable dose were eligible for this study. Patients were randomized 1:1 to receive either 2 g/kg of IVIg or placebo, administered every 4 weeks until week 16 (First Period). Patients were switched to the alternate treatment if they showed clinical deterioration in the First Period. After response assessment at week 16, all patients on placebo and those without deterioration on IVIg entered the open-label Extension Period, receiving 2 g/kg IVIg every 4 weeks for 24 weeks.
The primary efficacy endpoint was the proportion of responders in the IVIg vs placebo arm at week 16, where response was defined per 2016 ACR/EULAR Myositis Response Criteria of at least minimal improvement [Total Improvement Score (TIS) ≥20] and without deterioration at 2 consecutive visits up to week 16. TIS consists of composite response criteria, combining weighted improvement in 6 core set measures (CSMs), Global Disease Activity (Physician and Patient), manual muscle testing-8 (MMT-8), Health Assessment Questionnaire, extra-muscular disease activity, and muscle enzymes. Secondary endpoints included the mean change in individual CSMs, time to improvement in TIS, time to confirmed deterioration in the First Period, and the overall proportion of patients with deteriorations. Adverse events, including infusion reactions and thromboembolic events, were recorded.
The ProDERM study was the first to assess the long-term efficacy and safety of IVIg (Octagam 10%) in a placebo-controlled, blinded, randomized trial in DM. The study aimed to inform on the use of IVIg in the treatment of DM, and results are expected in Q3 2020.
NCT02728752.
皮肌炎（DM）是一种以独特的皮肤表现和肌肉无力为特征的炎症性肌病。静脉注射免疫球蛋白（IVIg）已被作为 DM 的辅助治疗方法在标签外使用，但由于在大型随机对照试验中缺乏疗效证据，因此不用于 DM。ProDERM（皮肌炎进展）研究的目的是评估在一项随机、安慰剂对照、双盲、III 期研究中，IVIg（Octagam 10%）在 DM 患者中的疗效、安全性和长期耐受性。
正在接受标准治疗且剂量稳定的活动性 DM 成年患者符合本研究条件。患者以 1:1 的比例随机接受 2g/kg 的 IVIg 或安慰剂，每 4 周给药 1 次，直至第 16 周（第 1 期）。如果患者在第 1 期出现临床恶化，则转换为另一种治疗方法。在第 16 周进行疗效评估后，所有安慰剂组患者和 IVIg 组无恶化的患者进入开放标签扩展期，每 4 周接受 2g/kg IVIg 治疗，共 24 周。
主要疗效终点为第 16 周 IVIg 组与安慰剂组的应答者比例，应答定义为 2016 年 ACR/EULAR 肌炎应答标准至少有微小改善[总改善评分（TIS）≥20]且在第 16 周前的 2 次连续访视中无恶化。TIS 由复合应答标准组成，包括 6 个核心集测量（CSMs）的加权改善，包括整体疾病活动度（医生和患者）、徒手肌力测试-8（MMT-8）、健康评估问卷、肌外疾病活动度和肌肉酶。次要终点包括各 CSM 的平均变化、TIS 改善时间、第 1 期确认恶化的时间以及恶化患者的总体比例。记录了不良事件，包括输注反应和血栓栓塞事件。
ProDERM 研究是首次在 DM 的安慰剂对照、盲法、随机试验中评估 IVIg（Octagam 10%）的长期疗效和安全性。该研究旨在为 IVIg 在 DM 治疗中的应用提供信息，预计将于 2020 年第三季度公布结果。
临床试验.gov 标识符：NCT02728752。
