Long-term follow-up of patients treated with caplacizumab and safety and efficacy of repeat caplacizumab use: Post-HERCULES study

Fecha de publicación: 01/01/2022

Autores de IIS La Fe

Javier De La Rubia Comos

Autor

Participantes ajenos a IIS La Fe

Scully M.
Pavenski K.
Metjian A.
Knöbl P.
Peyvandi F.
Cataland S.
Coppo P.
Kremer Hovinga J.A.
Minkue Mi Edou J.
De Passos Sousa R.
Callewaert F.
Gunawardena S.
Lin J.

Grupos

Hematología y Hemoterapia

Abstract

Introduction: Caplacizumab demonstrated efficacy and safety in patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) in the phase 3 HERCULES trial. However, data on long-term outcomes following caplacizumab treatment are limited. Objectives: The post-HERCULES trial (NCT02878603) evaluated long-term outcomes of patients with iTTP treated with caplacizumab in HERCULES and safety and efficacy of repeated caplacizumab use. Patients/Methods: Over 3 years of follow-up, patients could receive open-label caplacizumab with therapeutic plasma exchange (TPE) and immunosuppressive therapy (IST) in case of recurrence. Adverse events (AEs) were assessed during the overall study period (intention-to-observe [ITO] population) and during recurrences (recurrence population). TTP-related events (TTP-related death, recurrence, major thromboembolic events) were assessed in the efficacy ITO population (patients without recurrence during HERCULES or before post-HERCULES). Results: Among 104 enrolled patients, incidences of AEs and serious AEs were similar between patients who had received caplacizumab + TPE + IST during HERCULES (n = 75) and those treated with placebo + TPE + IST (placebo; n = 29). TTP-related events occurred in 8% of patients (4/49) randomized to caplacizumab during HERCULES versus 38% (11/29) randomized to placebo. Nineteen patients had =1 recurrence; 13 of these were treated with caplacizumab. The first recurrence episode was resolved or resolving for all patients treated with caplacizumab, including nine patients with repeat caplacizumab use. All second recurrences (6/6) were resolved. Safety profile of caplacizumab for treatment of recurrence was consistent with HERCULES; most bleeding events were nonserious. No major cases of organ dysfunction were observed. Conclusions: Long-term follow-up supports the safety and efficacy of caplacizumab for iTTP and its repeated use for recurrences. © 2022 Sanofi and The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.

Datos de la publicación

ISSN/ISSNe:: 1538-7933, 1538-7836
Tipo:: Article
Páginas:: 2810-2822
DOI:: 10.1111/jth.15892
PubMed:: 36138517
Enlace a otro recurso:: www.scopus.com
Factor de Impacto:: 3,815 SCImago ℠
Cuartil:: Q1 SCImago ℠

Documentos

No hay documentos

Métricas

Filiaciones

Scully M.:: Department of Haematology, UCLH and NIHR Cardiometabolic BRC, UCLH/UCL, London, United Kingdom

University College London Hospitals, London, United Kingdom
De la Rubia J.:: Hematology Department, Internal Medicine, School of Medicine and Dentistry, Catholic University of Valencia and Hospital LA FE, Valencia, Spain
Pavenski K.:: Departments of Medicine and Laboratory Medicine, St. Michael's Hospital and University of Toronto, Toronto, ON, Canada
Metjian A.:: Division of Hematology, Department of Medicine, University of Colorado–Anschutz Medical Center, Denver, CO, United States
Knöbl P.:: Division of Hematology and Hemostasis, Department of Medicine 1, Medical University of Vienna, Vienna, Austria
Peyvandi F.:: Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Università degli Studi di Milano, Milan, Italy
Cataland S.:: Department of Internal Medicine, Ohio State University, Columbus, OH, United States
Coppo P.:: Department of Hematology, Reference Center for Thrombotic Microangiopathies (CNR-MAT), Saint-Antoine University Hospital, AP-HP, Paris, France
Kremer Hovinga J.A.:: Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Minkue Mi Edou J.:: Formerly Sanofi, Zwijnaarde, Belgium
De Passos Sousa R.:: Formerly Sanofi, Lisbon, Portugal
Callewaert F.:: Formerly Sanofi, Diegem, Belgium
Gunawardena S.:: Sanofi, Cambridge, MA, United States
Lin J.:: Sanofi, Cambridge, MA, United States

Keywords

ADAMTS13 Protein; Follow-Up Studies; Humans; Purpura, Thrombotic Thrombocytopenic; Single-Domain Antibodies; caplacizumab; placebo; von Willebrand factor cleaving proteinase; caplacizumab; nanobody; thiamine triphosphorate; von Willebrand factor cleaving proteinase; acute heart infarction; adult; aged; allergy; Article; clinical feature; clinical practice; constipation; controlled study; diarrhea; drug efficacy; drug safety; epistaxis; female; headache; hematuria; human; hypersensitivity; hypokalemia; immune mediated thrombotic thrombocytopenic purpura; immunosuppressive treatment; injection site pain; ischemic stroke; major clinical study; male; middle aged; nausea; outcome assessment; paresthesia; phase 3 clinical trial; plasma exchange; protein function; pruritus; recurrent disease; rhinopharyngitis; Short Form 36; thromboembolism; thrombotic thrombocytopenic purpura; transient ischemic attack; urinary tract hemorrhage; vein embolism; vomiting; young adult; follow up; randomized con

Cita

Cita Bibliográfica