Factor XI inhibition with intravenous abelacimab may prevent venous thromboembolism (VTE) and reduce the risk of bleeding after total knee arthroplasty (TKA), according to findings published in The New England Journal of Medicine,
Researchers from this phase 2, open-label study enrolled patients who were scheduled to undergo elective TKA. Patients were randomly assigned to 3 different doses of abelacimab: 30 mg (n=102), 75 mg (n=99), or 150 mg (n=98). Each dose was administered after operation via a single intravenous infusion. A control group consisted of 101 randomly assigned patients who received subcutaneous 40 mg enoxaparin once per day.
The median age in the 150-mg abelacimab group was 68 years, whereas the median age in each of the other dose and treatment groups was 67 years. The median weight ranged from 86 kg in the 75-mg abelacimab group to 94 kg in the 40-mg enoxaparin group.
The primary efficacy outcome – VTE – was reported in 13% of patients in the 30-mg abelacimab group, 5% in the 75-mg abelacimab group, 4% of patients in the 150-mg abelacimab group, and 22% in the enoxaparin arm. The 3 abelacimab treatment arms were considered noninferior to enoxaparin.
Difference in risk for VTE (abelacimab minus enoxaparin) with 30-mg abelacimab was -9.2 percentage points (95% CI, -19.4 to 1.1; P =.08 for superiority). In contrast, the difference in risk for VTE with 75-mg abelacimab was -16.8 percentage points (95% CI, -26.0 to -7.6; P <.001 for superiority). The difference in risk for VTE with 150-mg abelacimab was -17.8 percentage points (95% CI, -26.7 to -8.8; P <.001 for superiority).
Through day 30, no clinically relevant bleeding events were observed in the enoxaparin group or the 150-mg abelacimab arm. Clinically relevant bleeding through day 30 was reported in 2% of patients in the 30-mg abelacimab group and 2% of patients in the 75-mg abelacimab arm.
Limitations of the study included its modest sample size as well as the open-label design in regard to abelacimab dose assignment.
Given these limitations, the researchers concluded that additional “studies are needed to determine whether anticoagulant strategies targeting factor XI can dissociate thrombosis from hemostasis.”
Disclosure: This clinical trial was supported by Anthos Therapeutics. Please see the original reference for a full list of disclosures.
Verhamme P, Yi BA, Segers A, et al; for the ANT-005 TKA Investigators. Abelacimab for prevention of venous thromboembolism. N Engl J Med. Published online July 19, 2021. doi:10.1056/NEJMoa2105872