Primary immune thrombocytopenia is an autoimmune disorder mediated partly by platelet autoantibodies, resulting in thrombocytopenia, bleeding, and constitutional symptoms. Efgartigimod, a first-in-class novel human IgG1 Fc fragment, binds the neonatal Fc receptor with high affinity and thus reduces serum IgG concentrations, including autoantibodies. The objective of this study was to evaluate the efficacy and safety of efgartigimod in adults with persistent and chronic primary immune thrombocytopenia. This phase 3, multicentre, randomised, double-blinded, placebo-controlled, 24-week study evaluated the efficacy and safety of intravenous efgartigimod in adults aged 18 years or older with chronic or persistent primary immune thrombocytopenia who had an average platelet count of less than 30 000, had responded to at least one previous immune thrombocytopenia therapy, and were on a concurrent therapy at baseline or had received at least a second previous immune thrombocytopenia therapy. The study took place in 71 participating sites from Asia, Europe, and North America. Patients were randomly assigned 2:1 to receive either efgartigimod (10 mg/kg) or placebo intravenously for the first 4 weeks, after which the dosing schedule could be altered to once per week or every other week depending on the patients' platelet count. The primary endpoint, evaluated in the chronic population, was sustained platelet count response (≥50 × 10 for at least 4 of the last 6 weeks). This study is registered with () and is completed. A total of 205 patients were screened from Dec 9, 2019, to Feb 3, 2022, and 131 (86 in the efgartigimod group; 45 in the placebo group) were randomly assigned. These patients represented a population with long-term disease who had a mean time since diagnosis of 10·6 years and 67% (88/131) of whom had received at least three previous immune thrombocytopenia treatments. 22% (17/78) of patients with chronic immune thrombocytopenia receiving efgartigimod reached the primary endpoint compared with 5% (2/40) of those receiving placebo (p=0·032; adjusted difference in response, 16% [95% CI 2·6–26·4]). The median number of weeks of disease control in patients with chronic immune thrombocytopenia was 2·0 (IQR 0·0–11·0) for efgartigimod versus 0·0 (0·0–1·0) for placebo (p=0·0009). Efgartigimod was well tolerated; most adverse events were mild to moderate in severity. The most common adverse events of interest in both groups were headache (16% in efgartigimod and 13% in placebo), haematuria (16% in efgartigimod and 16% in placebo), and petechiae (15% in efgartigimod and 27% in placebo). Efgartigimod significantly increased sustained platelet count responses compared with placebo in patients with chronic immune thrombocytopenia, including those who had received multiple previous immune thrombocytopenia therapies. Upon completion of the ADVANCE IV study, patients could enroll in the ongoing open-label extension. Subcutaneous efgartigimod is currently being evaluated in patients with immune thrombocytopenia in the ADVANCE SC+ trial. argenx.

中文翻译：

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新生儿 Fc 受体抑制剂 efgartigimod 对成人原发性免疫性血小板减少症 (ADVANCE IV) 的疗效和安全性：一项多中心、随机、安慰剂对照 3 期试验

原发性免疫性血小板减少症是一种部分由血小板自身抗体介导的自身免疫性疾病，导致血小板减少、出血和全身症状。Efgartigimod 是一种首创的新型人 IgG1 Fc 片段，以高亲和力结合新生儿 Fc 受体，从而降低血清 IgG 浓度，包括自身抗体。本研究的目的是评估 efgartigimod 对成人持续性和慢性原发性免疫性血小板减少症的疗效和安全性。这项 3 期、多中心、随机、双盲、安慰剂对照、为期 24 周的研究评估了静脉注射 efgartigimod 对 18 岁或以上患有慢性或持续性原发性免疫性血小板减少症且平均血小板计数低于超过 30,000 人，对至少一种先前的免疫性血小板减少症治疗有反应，并且在基线时正在接受同步治疗，或至少接受过第二种先前的免疫性血小板减少症治疗。该研究在来自亚洲、欧洲和北美的 71 个参与地点进行。患者以 2:1 的比例随机分配，在前 4 周内静脉注射 efgartigimod (10 mg/kg) 或安慰剂，之后根据患者的血小板计数，可以将给药方案更改为每周一次或每隔一周一次。在慢性人群中评估的主要终点是持续的血小板计数反应（过去 6 周中至少有 4 周≥50 × 10）。本研究已在（）处注册并已完成。2019年12月9日至2022年2月3日期间，共筛选了205名患者，其中131名患者（efgartigimod组86名；安慰剂组45名）被随机分配。这些患者代表了患有长期疾病的人群，自诊断以来平均时间为 10·6 年，其中 67% (88/131) 之前接受过至少 3 次免疫性血小板减少症治疗。接受 efgartigimod 治疗的慢性免疫性血小板减少症患者中有 22% (17/78) 达到主要终点，而接受安慰剂的患者只有 5% (2/40) 达到主要终点 (p=0·032；调整后的反应差异为 16% [95% CI 2·6–26·4]）。慢性免疫性血小板减少症患者的疾病控制中位周数，艾加替莫德组为 2·0 (IQR 0·0–11·0)，安慰剂组为 0·0 (0·0–1·0) (p=0·0) 0009）。Efgartigimod 耐受性良好；大多数不良事件的严重程度为轻度至中度。两组中最常见的不良事件是头痛（efgartigimod 中 16%，安慰剂 13%）、血尿（efgartigimod 中 16%，安慰剂 16%）和瘀点（efgartigimod 中 15%，安慰剂 27%） 。与安慰剂相比，Efgartigimod 显着增加了慢性免疫性血小板减少症患者的持续血小板计数反应，包括那些既往接受过多次免疫性血小板减少症治疗的患者。ADVANCE IV 研究完成后，患者可以参加正在进行的开放标签扩展。目前正在 ADVANCE SC+ 试验中对免疫性血小板减少症患者皮下注射 efgartigimod 进行评估。阿尔根克斯。