Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura

BACKGROUND In acquired thrombotic thrombocytopenic purpura (TTP), an immune-mediated deficiency of the von Willebrand factor-cleaving protease ADAMTS13 allows unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis, which result in thrombocytopenia, hemolytic anemia...

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Authors: Scully, M, Cataland, SR, Peyvandi, F, Coppo, P, Knöbl, P, Hovinga, JAK, Metjian, A, de la Rubia, J, Pavenski, K, Callewaert, F, Biswas, D, De Winter, H, Zeldin, RK
Format: article
Status:Published version
Publication Date:2019
Country:España
Institution:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repository:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p19122
Online Access:https://fisabio.portalinvestigacion.com/publicaciones/19122
Access Level:Open access
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spelling Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic PurpuraScully, MCataland, SRPeyvandi, FCoppo, PKnöbl, PHovinga, JAKMetjian, Ade la Rubia, JPavenski, KCallewaert, FBiswas, DDe Winter, HZeldin, RKBACKGROUND In acquired thrombotic thrombocytopenic purpura (TTP), an immune-mediated deficiency of the von Willebrand factor-cleaving protease ADAMTS13 allows unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis, which result in thrombocytopenia, hemolytic anemia, and tissue ischemia. Caplacizumab, an anti-von Willebrand factor humanized, bivalent variable-domain-only immunoglobulin fragment, inhibits interaction between von Willebrand factor multimers and platelets. METHODS In this double-blind, controlled trial, we randomly assigned 145 patients with TTP to receive caplacizumab (10-mg intravenous loading bolus, followed by 10 mg daily subcutaneously) or placebo during plasma exchange and for 30 days thereafter. The primary outcome was the time to normalization of the platelet count, with discontinuation of daily plasma exchange within 5 days thereafter. Key secondary outcomes included a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the trial treatment period; recurrence of TTP at any time during the trial; refractory TTP; and normalization of organ-damage markers. RESULTS The median time to normalization of the platelet count was shorter with caplacizumab than with placebo (2.69 days [95% confidence interval {CI}, 1.89 to 2.83] vs. 2.88 days [95% CI, 2.68 to 3.56], P = 0.01), and patients who received caplacizumab were 1.55 times as likely to have a normalization of the platelet count as those who received placebo. The percentage of patients with a composite outcome event was 74% lower with caplacizumab than with placebo (12% vs. 49%, P<0.001). The percentage of patients who had a recurrence of TTP at any time during the trial was 67% lower with caplacizumab than with placebo (12% vs. 38%, P<0.001). Refractory disease developed in no patients in the caplacizumab group and in three patients in the placebo group. Patients who received caplacizumab needed less plasma exchange and had a shorter hospitalization than those who received placebo. The most common adverse event was mucocutaneous bleeding, which was reported in 65% of the patients in the caplacizumab group and in 48% in the placebo group. During the trial treatment period, three patients in the placebo group died. One patient in the caplacizumab group died from cerebral ischemia after the end of the treatment period. CONCLUSIONS Among patients with TTP, treatment with caplacizumab was associated with faster normalization of the platelet count; a lower incidence of a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the treatment period; and a lower rate of recurrence of TTP during the trial than placebo.MASSACHUSETTS MEDICAL SOC2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/19122NEW ENGLAND JOURNAL OF MEDICINEISSN: 00284793ISSNe: 15334406reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p191222026-06-11T12:45:17Z
dc.title.none.fl_str_mv Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura
title Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura
spellingShingle Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura
Scully, M
title_short Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura
title_full Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura
title_fullStr Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura
title_full_unstemmed Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura
title_sort Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura
dc.creator.none.fl_str_mv Scully, M
Cataland, SR
Peyvandi, F
Coppo, P
Knöbl, P
Hovinga, JAK
Metjian, A
de la Rubia, J
Pavenski, K
Callewaert, F
Biswas, D
De Winter, H
Zeldin, RK
author Scully, M
author_facet Scully, M
Cataland, SR
Peyvandi, F
Coppo, P
Knöbl, P
Hovinga, JAK
Metjian, A
de la Rubia, J
Pavenski, K
Callewaert, F
Biswas, D
De Winter, H
Zeldin, RK
author_role author
author2 Cataland, SR
Peyvandi, F
Coppo, P
Knöbl, P
Hovinga, JAK
Metjian, A
de la Rubia, J
Pavenski, K
Callewaert, F
Biswas, D
De Winter, H
Zeldin, RK
author2_role author
author
author
author
author
author
author
author
author
author
author
author
description BACKGROUND In acquired thrombotic thrombocytopenic purpura (TTP), an immune-mediated deficiency of the von Willebrand factor-cleaving protease ADAMTS13 allows unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis, which result in thrombocytopenia, hemolytic anemia, and tissue ischemia. Caplacizumab, an anti-von Willebrand factor humanized, bivalent variable-domain-only immunoglobulin fragment, inhibits interaction between von Willebrand factor multimers and platelets. METHODS In this double-blind, controlled trial, we randomly assigned 145 patients with TTP to receive caplacizumab (10-mg intravenous loading bolus, followed by 10 mg daily subcutaneously) or placebo during plasma exchange and for 30 days thereafter. The primary outcome was the time to normalization of the platelet count, with discontinuation of daily plasma exchange within 5 days thereafter. Key secondary outcomes included a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the trial treatment period; recurrence of TTP at any time during the trial; refractory TTP; and normalization of organ-damage markers. RESULTS The median time to normalization of the platelet count was shorter with caplacizumab than with placebo (2.69 days [95% confidence interval {CI}, 1.89 to 2.83] vs. 2.88 days [95% CI, 2.68 to 3.56], P = 0.01), and patients who received caplacizumab were 1.55 times as likely to have a normalization of the platelet count as those who received placebo. The percentage of patients with a composite outcome event was 74% lower with caplacizumab than with placebo (12% vs. 49%, P<0.001). The percentage of patients who had a recurrence of TTP at any time during the trial was 67% lower with caplacizumab than with placebo (12% vs. 38%, P<0.001). Refractory disease developed in no patients in the caplacizumab group and in three patients in the placebo group. Patients who received caplacizumab needed less plasma exchange and had a shorter hospitalization than those who received placebo. The most common adverse event was mucocutaneous bleeding, which was reported in 65% of the patients in the caplacizumab group and in 48% in the placebo group. During the trial treatment period, three patients in the placebo group died. One patient in the caplacizumab group died from cerebral ischemia after the end of the treatment period. CONCLUSIONS Among patients with TTP, treatment with caplacizumab was associated with faster normalization of the platelet count; a lower incidence of a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the treatment period; and a lower rate of recurrence of TTP during the trial than placebo.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/19122
url https://fisabio.portalinvestigacion.com/publicaciones/19122
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MASSACHUSETTS MEDICAL SOC
publisher.none.fl_str_mv MASSACHUSETTS MEDICAL SOC
dc.source.none.fl_str_mv NEW ENGLAND JOURNAL OF MEDICINE
ISSN: 00284793
ISSNe: 15334406
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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