Efficacy and safety of open-label caplacizumab in patients with exacerbations of acquired thrombotic thrombocytopenic purpura in the HERCULES study
Por:
Knoebl P, Cataland S, Peyvandi F, Coppo P, Scully M, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Minkue Mi Edou J, De Winter H and Callewaert F
Publicada:
1 feb 2020
Ahead of Print:
9 dic 2019
Resumen:
Background Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, life-threatening autoimmune thrombotic microangiopathy. Caplacizumab, an anti-von Willebrand Factor Nanobody (R), is effective for treating aTTP episodes and is well tolerated. Objectives and methods In the phase 3 HERCULES trial (NCT02553317), patients with aTTP received double-blind caplacizumab or placebo during daily therapeutic plasma exchange (TPE) and for >= 30 days thereafter. Patients who experienced an exacerbation while on blinded study drug treatment switched to receive open-label caplacizumab plus re-initiation of daily TPE. Exacerbations were defined as recurrence of disease occurring within 30 days after cessation of daily TPE.
Results Thirty-one patients (placebo, n = 28; caplacizumab, n = 3) had an exacerbation during double-blind treatment. Twenty-eight patients switched to open-label caplacizumab (placebo, n = 26; caplacizumab, n = 2); the three others discontinued upon exacerbation. Median time to platelet count response (>= 150 x 10(9)/L) was 3.49 days upon receiving caplacizumab. There were no deaths. During open-label treatment, further exacerbation or a major thromboembolic event (vena cava thrombosis) was experienced by one patient (3.6%) each. Consistent with the double-blind phase, the most frequent treatment-emergent adverse events were catheter site hemorrhage (28.6%), headache (21.4%), and epistaxis (17.9%). Conclusions These results suggest that caplacizumab was efficacious and well tolerated in patients with aTTP who experienced a disease exacerbation during double-blind treatment in HERCULES.
Filiaciones:
Knoebl P:
Department of Medicine 1, Division of Hematology and Hemostasis, Medical University of Vienna, Austria
Cataland S:
Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
Peyvandi F:
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, and Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
Coppo P:
Department of Hematology, Reference Center for Thrombotic Microangiopathies (CNR-MAT), Saint-Antoine University Hospital, AP-HP, Paris, France
Scully M:
Department of Haematology, University College London Hospital, Cardiometabolic Programme-NIHR UCLH/UCL BRC, London, United Kingdom
Kremer Hovinga JA:
Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Metjian A:
Department of Medicine, Duke University School of Medicine, Durham, NC, USA
:
Hematology Department, Internal Medicine, School of Medicine and Dentistry, Catholic University of Valencia and Hospital Doctor Peset, Valencia, Spain
Pavenski K:
Departments of Medicine and Laboratory Medicine, St. Michael's Hospital and University of Toronto, Toronto, ON, Canada
Minkue Mi Edou J:
Clinical Development, Ablynx, a Sanofi company, Ghent, Belgium
De Winter H:
Formerly Clinical Development, Ablynx, a Sanofi company, Ghent, Belgium
Callewaert F:
Medical Affairs, Sanofi, Diegem, Belgium
Green Published, hybrid
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