Osocimab預防膝關節置換術後靜脈血栓栓塞

Osocimab預防膝關節置換術後靜脈血栓栓塞

作者：

小柯機器人

發布時間：2020/1/16 14:14:28

加拿大麥克馬斯特大學Jeffrey I. Weitz聯合美國俄克拉荷馬大學健康科學中心Gary E. Raskob課題組在研究中取得進展。他們的最新研究探索了Osocimab在預防膝關節置換術患者靜脈血栓栓塞中的作用。該研究於2020年1月14日發表於國際一流學術期刊《美國醫學會雜誌》上。

凝血因子XIa抑制血栓形成的療效尚不清楚。Osocimab是一種長效的完全人源化單克隆抗體，可抑制因子XIa。

為了比較不同劑量Osocimab與依諾肝素和阿哌沙班在膝關節置換術後預防血栓形成的作用，2017年10月至2018年8月，研究組在13個國家的54家醫院進行了一項隨機、開放標籤、試驗者盲、臨床2期的非劣效性試驗，共招募了813名接受單側膝關節置換術的成年患者，平均年齡為66.5歲，74.2%為女性。

將這些患者隨機分組，其中107名術後單次靜脈注射Osocimab 0.3mg/kg，65名注射0.6mg/kg，108名注射1.2mg/kg，106名注射1.8mg/kg；109名術前靜脈注射Osocimab 0.3mg/kg，108名注射1.8mg/kg；105名每日一次皮下注射依諾肝素，105名每日口服阿哌沙班，至少為期10天。術後10-13天，採用雙側靜脈造影對深靜脈血栓或肺栓塞進行評估。

共有600名患者納入最終分析。其中術後Osocimab 0.3mg/kg組中有23.7%的患者發生靜脈血栓栓塞，0.6mg/kg組中有15.7%，1.2mg/kg組中有16.5%，1.8mg/kg組中有17.9%；術前Osocimab 0.3mg/kg組中有29.9%，1.8mg/kg組中有11.3%；依諾肝素組中有26.3%，阿哌沙班組中有14.5%。

與依諾肝素相比，術後給予Osocimab符合非劣效性標準，0.6mg/kg劑量的風險差異為10.6%，1.2mg/kg為9.9%，1.8mg/kg為8.4%；術前Osocimab劑量為1.8mg/kg顯著優於依諾肝素，風險差異為15.1%。術後和術前Osocimab劑量為0.3mg/kg均不符合非劣效性標準，風險差異分別為2.6%和-3.6%。Osocimab組中有4.7%的患者出現嚴重或臨床相關的非大出血，依諾肝素組為5.9%，阿哌沙班組為2%。

總之，對於接受膝關節置換術的患者，與依諾肝素相比，術後給予0.6mg/kg、1.2mg/kg和1.8mg/kg的Osocimab在術後10-13天靜脈血栓栓塞方面符合非劣效性標準，而術前1.8mg/kg的Osocimab符合優勢標準。仍需要進一步研究來確定Osimimb預防血栓栓塞的有效性和安全性。

附：英文原文

Title: Effect of Osocimab in Preventing Venous Thromboembolism Among Patients Undergoing Knee Arthroplasty: The FOXTROT Randomized Clinical Trial

Author: Jeffrey I. Weitz, Rupert Bauersachs, Bastian Becker, Scott D. Berkowitz, Maria C. S. Freitas, Michael R. Lassen, Carola Metzig, Gary E. Raskob

Issue&Volume: 2020/01/14

Abstract:

Importance  The efficacy of factor XIa inhibition for thromboprophylaxis is unknown. Osocimab is a long-acting, fully human monoclonal antibody that inhibits factor XIa.

Objective  To compare different doses of osocimab with enoxaparin and apixaban for thromboprophylaxis in patients who have undergone knee arthroplasty.

Design, Setting, and Participants  Randomized, open-label, adjudicator-blinded, phase 2 noninferiority trial with observer blinding for osocimab doses, conducted at 54 hospitals in 13 countries. Adult patients undergoing unilateral knee arthroplasty were randomized from October 2017 through August 2018 and followed up until January 2019.

Interventions  Single intravenous osocimab postoperative doses of 0.3 mg/kg (n = 107), 0.6 mg/kg (n = 65), 1.2 mg/kg (n = 108), or 1.8 mg/kg (n = 106); preoperative doses of 0.3 mg/kg (n = 109) or 1.8 mg/kg (n = 108); or 40 mg of subcutaneous enoxaparin once daily (n = 105) or 2.5 mg of oral apixaban twice daily (n = 105) for at least 10 days or until venography.

Main Outcomes and Measures  The primary outcome was venous thromboembolism incidence between 10 and 13 days postoperatively (assessed by mandatory bilateral venography performed 10 to 13 days after surgery or confirmed symptomatic deep vein thrombosis or pulmonary embolism). A 5% noninferiority margin compared with enoxaparin was chosen. The primary safety outcome of major or clinically relevant nonmajor bleeding was assessed until 10 to 13 days postoperatively.

Results  Of 813 randomized participants (mean [SD] age, 66.5 years [8.2 years]; body mass index, 32.7 [5.7]; and 74.2% women), 600 were included in the per-protocol population used for the primary analysis. The primary outcome occurred in 18 patients (23.7%) receiving 0.3 mg/kg, 8 (15.7%) receiving 0.6 mg/kg, 13 (16.5%) receiving 1.2 mg/kg, and 14 (17.9%) receiving 1.8 mg/kg of osocimab postoperatively; 23 (29.9%) receiving 0.3 mg/kg and 9 (11.3%) receiving 1.8 mg/kg of osocimab preoperatively; 20 (26.3%) receiving enoxaparin; and 12 (14.5%) receiving apixaban. Osocimab given postoperatively met criteria for noninferiority compared with enoxaparin with risk differences (1-sided 95% CIs) of 10.6% (95% CI, –1.2% to ∞) at the 0.6-mg/kg dose; 9.9% (95% CI, –0.9% to ∞) at the 1.2-mg/kg dose, and 8.4% (95% CI, –2.6 to ∞) at the 1.8-mg/kg dose. The preoperative dose of 1.8 mg/kg of osocimab met criteria for superiority compared with enoxaparin with a risk difference of 15.1%; 2-sided 90% CI, 4.9% to 25.2%). Postoperative and preoperative doses of 0.3 mg/kg of osocimab did not meet the prespecified criteria for noninferiority, with risk differences (1-sided 95% CIs) of 2.6% (95% CI, –8.9% to ∞) and –3.6% (95% CI, –15.5% to ∞), respectively. Major or clinically relevant nonmajor bleeding was observed in up to 4.7% of those receiving osocimab, 5.9% receiving enoxaparin, and 2% receiving apixaban.

Conclusions and Relevance  Among patients undergoing knee arthroplasty, postoperative osocimab 0.6 mg/kg, 1.2 mg/kg, and 1.8 mg/kg met criteria for noninferiority compared with enoxaparin, and the preoperative 1.8-mg/kg dose of osocimab met criteria for superiority compared with enoxaparin for the primary outcome of incidence of venous thromboembolism at 10 to 13 days postoperatively. Further studies are needed to establish efficacy and safety of osocimab relative to standard thromboprophylaxis.

DOI: 10.1001/jama.2019.20687

Source: https://jamanetwork.com/journals/jama/article-abstract/2758600