Abelacimab for Prevention of Venous Thromboembolism.

Adult Aged Aged, 80 and over Antibodies, Monoclonal, Humanized / administration & dosage Anticoagulants / administration & dosage Arthroplasty, Replacement, Knee Dose-Response Relationship, Drug Enoxaparin / adverse effects Factor XI / antagonists & inhibitors Female Hemorrhage / chemically induced Humans Infusions, Intravenous Injections, Subcutaneous Male Middle Aged Partial Thromboplastin Time Postoperative Complications / prevention & control Venous Thromboembolism / prevention & control

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
12 08 2021
Historique:
pubmed: 24 7 2021
medline: 24 8 2021
entrez: 23 7 2021
Statut: ppublish

Résumé

The role of factor XI in the pathogenesis of postoperative venous thromboembolism is uncertain. Abelacimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precursor) conformation. In this open-label, parallel-group trial, we randomly assigned 412 patients who were undergoing total knee arthroplasty to receive one of three regimens of abelacimab (30 mg, 75 mg, or 150 mg) administered postoperatively in a single intravenous dose or to receive 40 mg of enoxaparin administered subcutaneously once daily. The primary efficacy outcome was venous thromboembolism, detected by mandatory venography of the leg involved in the operation or objective confirmation of symptomatic events. The principal safety outcome was a composite of major or clinically relevant nonmajor bleeding up to 30 days after surgery. Venous thromboembolism 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, as compared with 22 of 101 patients (22%) in the enoxaparin group. The 30-mg abelacimab regimen was noninferior to enoxaparin, and the 75-mg and 150-mg abelacimab regimens were superior to enoxaparin (P<0.001). Bleeding occurred in 2%, 2%, and none of the patients in the 30-mg, 75-mg, and 150-mg abelacimab groups, respectively, and in none of the patients in the enoxaparin group. This trial showed that factor XI is important for the development of postoperative venous thromboembolism. Factor XI inhibition with a single intravenous dose of abelacimab after total knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding. (Funded by Anthos Therapeutics; ANT-005 TKA EudraCT number, 2019-003756-37.).

Sections du résumé

BACKGROUND
The role of factor XI in the pathogenesis of postoperative venous thromboembolism is uncertain. Abelacimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precursor) conformation.
METHODS
In this open-label, parallel-group trial, we randomly assigned 412 patients who were undergoing total knee arthroplasty to receive one of three regimens of abelacimab (30 mg, 75 mg, or 150 mg) administered postoperatively in a single intravenous dose or to receive 40 mg of enoxaparin administered subcutaneously once daily. The primary efficacy outcome was venous thromboembolism, detected by mandatory venography of the leg involved in the operation or objective confirmation of symptomatic events. The principal safety outcome was a composite of major or clinically relevant nonmajor bleeding up to 30 days after surgery.
RESULTS
Venous thromboembolism 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, as compared with 22 of 101 patients (22%) in the enoxaparin group. The 30-mg abelacimab regimen was noninferior to enoxaparin, and the 75-mg and 150-mg abelacimab regimens were superior to enoxaparin (P<0.001). Bleeding occurred in 2%, 2%, and none of the patients in the 30-mg, 75-mg, and 150-mg abelacimab groups, respectively, and in none of the patients in the enoxaparin group.
CONCLUSIONS
This trial showed that factor XI is important for the development of postoperative venous thromboembolism. Factor XI inhibition with a single intravenous dose of abelacimab after total knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding. (Funded by Anthos Therapeutics; ANT-005 TKA EudraCT number, 2019-003756-37.).

Identifiants

DOI: 10.1056/NEJMoa2105872 PMID: 34297496
pubmed: 34297496
doi: 10.1056/NEJMoa2105872
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
Anticoagulants 0
Enoxaparin 0
Factor XI 9013-55-2
abelacimab KX1N4TV7UY

Banques de données

EudraCT
['2019-003756-37']

Types de publication

Comparative Study Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

609-617

Investigateurs

Peter Verhamme (P)
Harry Buller (H)
Gary Raskob (G)
Jeffrey Weitz (J)
Annelise Segers (A)
Dan Bloomfield (D)
Deb Freedholm (D)
Thomas Vanassche (T)
Ruse S Angelov (RS)
Plovdiv V Stavrev (PV)
Sofia P Kinov (SP)
Liepāja U Argalis (LU)
Valmiera A Baurovskis (VA)
Riga A Peredistijs (RA)
Riga S Petronis (RS)
Riga M Zambrans (RM)
Kaunas J Belickas (KJ)
Klaipėda A Cebatorius (KA)
Vilnius G Kvederas (VG)
Kaunas A Smailys (KA)
Nizhny Novgorod V Zagrekov (NNV)
Kyiv M Ankin (KM)
Ivano-Frankivsk V Sulyma (IV)
Chernivtsi Y Vasylchyshyn (CY)

Commentaires et corrections

Type : CommentIn
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Informations de copyright

Copyright © 2021 Massachusetts Medical Society.

Auteurs

Peter Verhamme (P)

From KU Leuven Department of Cardiovascular Sciences, Vascular Medicine and Hemostasis, Leuven, Belgium (P.V.); Anthos Therapeutics, Cambridge, MA (B.A.Y., J.S., D.B.); International Trial Expertise Advisory and Services (A.S.) and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam (H.R.B.) - both in Amsterdam; Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.); and the Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada (J.I.W.).

B Alexander Yi (BA)

From KU Leuven Department of Cardiovascular Sciences, Vascular Medicine and Hemostasis, Leuven, Belgium (P.V.); Anthos Therapeutics, Cambridge, MA (B.A.Y., J.S., D.B.); International Trial Expertise Advisory and Services (A.S.) and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam (H.R.B.) - both in Amsterdam; Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.); and the Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada (J.I.W.).

Annelise Segers (A)

From KU Leuven Department of Cardiovascular Sciences, Vascular Medicine and Hemostasis, Leuven, Belgium (P.V.); Anthos Therapeutics, Cambridge, MA (B.A.Y., J.S., D.B.); International Trial Expertise Advisory and Services (A.S.) and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam (H.R.B.) - both in Amsterdam; Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.); and the Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada (J.I.W.).

Janeen Salter (J)

From KU Leuven Department of Cardiovascular Sciences, Vascular Medicine and Hemostasis, Leuven, Belgium (P.V.); Anthos Therapeutics, Cambridge, MA (B.A.Y., J.S., D.B.); International Trial Expertise Advisory and Services (A.S.) and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam (H.R.B.) - both in Amsterdam; Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.); and the Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada (J.I.W.).

Daniel Bloomfield (D)

From KU Leuven Department of Cardiovascular Sciences, Vascular Medicine and Hemostasis, Leuven, Belgium (P.V.); Anthos Therapeutics, Cambridge, MA (B.A.Y., J.S., D.B.); International Trial Expertise Advisory and Services (A.S.) and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam (H.R.B.) - both in Amsterdam; Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.); and the Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada (J.I.W.).

Harry R Büller (HR)

From KU Leuven Department of Cardiovascular Sciences, Vascular Medicine and Hemostasis, Leuven, Belgium (P.V.); Anthos Therapeutics, Cambridge, MA (B.A.Y., J.S., D.B.); International Trial Expertise Advisory and Services (A.S.) and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam (H.R.B.) - both in Amsterdam; Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.); and the Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada (J.I.W.).

Gary E Raskob (GE)

From KU Leuven Department of Cardiovascular Sciences, Vascular Medicine and Hemostasis, Leuven, Belgium (P.V.); Anthos Therapeutics, Cambridge, MA (B.A.Y., J.S., D.B.); International Trial Expertise Advisory and Services (A.S.) and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam (H.R.B.) - both in Amsterdam; Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.); and the Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada (J.I.W.).

Jeffrey I Weitz (JI)

From KU Leuven Department of Cardiovascular Sciences, Vascular Medicine and Hemostasis, Leuven, Belgium (P.V.); Anthos Therapeutics, Cambridge, MA (B.A.Y., J.S., D.B.); International Trial Expertise Advisory and Services (A.S.) and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam (H.R.B.) - both in Amsterdam; Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.); and the Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada (J.I.W.).

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents hématologiques › Anticoagulants › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › Procédures de chirurgie opératoire › Implantation de prothèse › Arthroplastie prothétique › Arthroplastie prothétique de genou › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes toxicologiques › Relation dose-effet des médicaments › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › Glucides › Polyosides › Glycosaminoglycanes › Héparine › Héparine bas poids moléculaire › Énoxaparine › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › Facteurs biologiques › Facteurs de la coagulation sanguine › Facteur XI › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Hémorragie › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Perfusions parentérales › Perfusions veineuses › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Injections › Injections sous-cutanées › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Temps partiel de thromboplastine › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Complications postopératoires › Abelacimab for Prevention of Venous Thromboembolism.
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Embolie et thrombose › Thromboembolie › Thromboembolisme veineux › Abelacimab for Prevention of Venous Thromboembolism.