Key Points

• This industry-promoted, phase-2, randomized, parallel-group trial compared the efficacy and safety of abelacimab, a fully human monoclonal antibody against factor XI (FXI), with enoxaparin in 412 patients undergoing elective, unilateral total knee arthroplasty (TKA). Patients (mean age, 67 years; 81% female) were randomly assigned in a 1:1:1:1 ratio to receive one of three regimens of abelacimab (30, 75, or 150 mg in a single intravenous infusion, 5 h after surgery) or enoxaparin 40 mg administered subcutaneously once daily (starting either the evening before or 12 hours after surgery) for a median of 9 days. Assignment to enoxaparin or abelacimab was open label, whereas assignment to an abelacimab regimen was blinded.
• Adjudicated venous thromboembolism (VTE) was the primary efficacy outcome. VTE was defined as a composite of asymptomatic deep-vein thrombosis (DVT; detected by mandatory unilateral venography performed between day 8 and day 12 after surgery), confirmed symptomatic VTE (symptomatic DVT of the leg or nonfatal pulmonary embolism (PE)], fatal PE, or unexplained death for which PE could not be ruled out. Adjudicated clinically relevant bleeding, a composite of major or clinically relevant nonmajor bleeding up to 30 days after surgery, was the principal safety outcome.
• VTE occurred in 4%, 5%, and 13% of patients in the 150-, 75-, and 30-mg abelacimab groups, respectively, compared with 22% of patients in the enoxaparin group. All three abelacimab regimens met the primary criterion for noninferiority to enoxaparin. The 75- and 150-mg regimens were both superior to enoxaparin (P < 0.001). Clinically relevant bleeding occurred in 2 of 102 patients (2%) assigned to receive abelacimab 30 mg, 2 of 104 (2%) patients assigned to receive 75 mg, none of 99 patients in the 150-mg group, and none of 104 patients in the enoxaparin group. Serious adverse events occurred during the trial in 1%, 3% and 1% of the patients in the 30-, 75-, and 150-mg abelacimab groups, respectively, and in none of the patients in the enoxaparin group.
• FXI activity and free FXI levels were inversely correlated with plasma concentrations of abelacimab, which increased in a dose-dependent fashion and declined slowly over 110 days.

The results of Abelacimab for Prevention of Venous Thromboembolism have been published in N Engl J Med. doi:10.1056/NEJMoa2105872.

中文翻译：

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Abelacimab 和因子 XI 抑制：预防静脉血栓栓塞的新机制

关键点

• 这项行业推广的 2 期随机平行组试验在 412 名接受选择性单侧全膝关节置换术 (TKA) 的患者中比较了 abelacimab（一种针对因子 XI (FXI) 的全人源单克隆抗体）与依诺肝素的疗效和安全性. 患者（平均年龄 67 岁；81% 女性）以 1:1:1:1 的比例随机分配接受三种 abelacimab 方案之一（30、75 或 150 mg，单次静脉输注，5 小时后手术）或依诺肝素 40 mg 每天一次皮下给药（从手术前一晚或手术后 12 小时开始），中位时间为 9 天。依诺肝素或 abelacimab 的分配是开放标签，而 abelacimab 方案的分配是不知情的。
• 经裁定的静脉血栓栓塞 (VTE) 是主要疗效结果。VTE 被定义为无症状深静脉血栓形成（DVT；通过在手术后第 8 天和第 12 天之间进行的强制性单侧静脉造影检测）、确诊的有症状的 VTE（腿部有症状的 DVT 或非致命性肺栓塞（PE））、致命的PE，或不能排除 PE 的不明原因死亡。经判定的临床相关出血，包括手术后 30 天内的大出血或临床相关的非大出血的复合，是主要的安全结果。
• 150、75 和 30 毫克 abelacimab 组的 VTE 发生率分别为 4%、5% 和 13%，而依诺肝素组为 22%。所有三种 abelacimab 方案均符合非劣效于依诺肝素的主要标准。75 和 150 毫克方案均优于依诺肝素（P < 0.001）。分配到接受 abelacimab 30 mg 的 102 名患者中的 2 名 (2%)、分配到 75 mg 的 104 名患者中的 2 名 (2%)、150 毫克组中的 99 名患者中均未发生临床相关出血，以及 104 名患者中均未发生临床相关出血在依诺肝素组。在试验期间，30-、75- 和 150-mg abelacimab 组中 1%、3% 和 1% 的患者发生严重不良事件，依诺肝素组中没有患者发生。
• FXI 活性和游离 FXI 水平与 abelacimab 的血浆浓度呈负相关，后者以剂量依赖性方式增加，并在 110 天内缓慢下降。

Abelacimab 用于预防静脉血栓栓塞的结果已发表在N Engl J Med 上。doi:10.1056/NEJMoa2105872。