Abelacimab Effective in Prevention of VTE, Including Low Bleeding Risk

Jeffrey I. Weitz, MD

Data has shown the effectiveness of factor XI in postoperative venous thromboembolism (VTE) is still unknown, particularly when compared to preoperative inhibition.

A recent phase 2 study compared the efficacy and safety of abelcaimab administered postoperative in comparison to the efficacy and safety of enoxaparin in patients undergoing total knee arthroplasty.

Investigators, led by Jeffrey I. Weitz, MD, Thrombosis and Atherosclerosis Research Institute, found a single intravenous dose of abelacimab after total knee arthroplasty was effective in the prevention of venous thromboembolism, including a low risk of bleeding.

Study

The team performed a phase 2, prospective, randomized, parallel group trial and compared 3 regimens of abelacimab at 30 mg, 75 mg, or 150 mg to 40 mg of enoxaparin.

They noted that assignment to either agent was conducted as open-label and the assignment to abelacimab was blinded.

In addition, abelacimab was administered in a single intravenous infusion over 30-60 minutes in a period 4 - 8 hours after surgery.

Further, enoxaparin was administered subcutaneously once daily, either the evening before or approximately 12 hours after surgery.

Patients aged 18 - 80 years undergoing elective primary unilateral total knee arthroplasty, with a body weight of 50 to 130 kg were eligible for the trial.

Exclusion criteria included high risk of bleeding, history of VTE, estimate glomerular filtration rate >60ml/m/1.73mm2and clinically significant liver disease.

The team’s primary efficacy outcome was VTE, defined as a composite of asymptomatic deep-vein thrombosis, confirmed symptomatic VTE, fatal pulmonary embolism, or unexplained death. It was detected by venography of the leg or confirmation of symptomatic events.

Safety outcomes included adjudicated clinically relevant bleeding from randomization until venography was completed and from randomization through day 30 after surgery.

Results

A total of 412 patients at 16 centers in 5 countries were randomized from June - November 2020.

Investigators obtained venograms from 400 of 409 (98%) patients who received trial medication.

They noted that VTE occurred in 13 of 102 patients (13%) in the 30-mg abelacimab group, 5 of 99 patients (5%) in the 75-mg abelacimab group, and 4 of 98 patients (4%) in the 150-mg abelacimab group.

In comparison, 22 of 101 patients (22%) had VTE occur in the enoxaparin group.

Further, the difference in risk (abelacimab minus enoxaparin) with the 30-mg abelacimab regimen was -9.2% (95% CI, -19.4 - 1.1, P = .08).

In addition, the difference with the 75-mg abelacimab regimen was -16.8% (95% CI, -26.0 to -7.6, P <.001) and the difference with the 150-mg abelacimab regimen was -17.8% (95% CI, -26.7 to -8.8, P <.001).

The team observed bleeding occurred in 2% in the 30-mg, 2% in the 75-mg, and none of the patients in the 150-mg abelacimab groups. No bleeding occurred in patients in the enoxaparin group.

Conclusion

Investigators concluded abelacimab reduced the risk of postoperative thromboembolism at a greater extent compared to conventional anticoagulants, such as enoxaparin.

“Therefore, this trial showed that the postoperative initiation of factor XI inhibition was an effective method for reducing the risk of venous thromboembolism after total knee arthroplasty and was associated with a low risk of bleeding,” investigators wrote.

The study, “Abelacimab for Prevention of Venous Thromboembolism,” was published online in the New England Journal of Medicine.