Single abelacimab dose reduces VTE after knee replacement surgery
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A single IV dose of the factor XI monoclonal antibody abelacimab appeared superior to daily enoxaparin for preventing venous thromboembolism after total knee arthroplasty, according to randomized study results.
The results — presented at International Society on Thrombosis and Hemostasis Congress and published in The New England Journal of Medicine — showed abelacimab (Anthos Therapeutics) reduced blood clot risk by about 80% without increasing bleeding risk.
The findings illustrate the importance of factor XI in the development of postoperative VTE, researchers concluded.
“We expect factor XI to be a safer target for new anticoagulants than the targets of currently available anticoagulants because patients with congenital factor XI deficiency are at reduced risk for clots but rarely have spontaneous bleeding," Jeffrey Weitz, MD, FRCP, FACP, FCCP, professor of medicine and professor of biochemistry and biomedical sciences at McMaster University’s Michael G. DeGroote School of Medicine and executive director of the Thrombosis and Atherosclerosis Research Institute, said in a press release.
Patients who undergo knee replacement typically undergo anti-clotting therapy with enoxaparin or other anticoagulants that require daily administration.
Factor XI’s role in the pathogenesis of postoperative VTE has not been established.
Abelacimab — a fully human monoclonal antibody — binds to activated and inactive forms of factor XI, preventing its activation and activity and, thus, halting clot formation.
Weitz and colleagues conducted an open-label, parallel-group trial that included patients undergoing total knee arthroplasty.
Researchers randomly assigned 299 patients to receive abelacimab regimens dosed postoperatively in single IV doses of 30 mg, (n = 102), 75 mg (n = 99) or 150 mg (n = 98). The other 101 patients received 40 mg enoxaparin administered in a once-daily subcutaneous dose.
VTE incidence detected by mandatory venography of the leg or objective confirmation of symptomatic events served as the primary efficacy outcome.
A composite of major or clinically relevant nonmajor bleeding up to 30 days after surgery served as the principal safety outcome.
Researchers reported lower VTE rates in all three abelacimab groups — 13% for the 30-mg dose, 5% for the 75-mg group and 4% of the 150-mg dose — than the enoxaparin group (22%).
The 30-mg abelacimab regimen appeared noninferior to the enoxaparin regimen, whereas the 75-mg and 150-mg abelacimab regimens significantly reduced VTE compared with enoxaparin (P < .001 for both).
Researchers reported bleeding among 2% of patients assigned the 30-mg abelacimab dose and 2% of patients assigned the 75-mg dose. No patients assigned the 150-mg abelacimab dose or enoxaparin experienced bleeding.
“This success of abelacimab in this study provides the foundation for its use for prevention of stroke [among] patients with atrial fibrillation, and for treatment of deep vein thrombosis and pulmonary embolism ... [among] patients with cancer,” Weitz said.
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