Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura

BACKGROUND Acquired thrombotic thrombocytopenic purpura (TTP) is caused by aggregation of platelets on ultralarge von Willebrand factor multimers. This microvascular thrombosis causes multiorgan ischemia with potentially life-threatening complications. Daily plasma exchange and immunosuppressive the...

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Autores: Peyvandi, F, Scully, M, Hovinga, JAK, Cataland, S, Knobl, P, Wu, HF, Artoni, A, Westwood, JP, Taleghani, MM, Jilma, B, Callewaert, F, Ulrichts, H, Duby, C, Tersago, D, TITAN Investigators
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Recursos:INCLIVA
Repositorio:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p4707
Acesso em linha:https://incliva.portalinvestigacion.com/publicaciones/4707
Access Level:acceso abierto
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spelling Caplacizumab for Acquired Thrombotic Thrombocytopenic PurpuraPeyvandi, FScully, MHovinga, JAKCataland, SKnobl, PWu, HFArtoni, AWestwood, JPTaleghani, MMJilma, BCallewaert, FUlrichts, HDuby, CTersago, DTITAN InvestigatorsBACKGROUND Acquired thrombotic thrombocytopenic purpura (TTP) is caused by aggregation of platelets on ultralarge von Willebrand factor multimers. This microvascular thrombosis causes multiorgan ischemia with potentially life-threatening complications. Daily plasma exchange and immunosuppressive therapies induce remission, but mortality and morbidity due to microthrombosis remain high. METHODS Caplacizumab, an anti-von Willebrand factor humanized single-variable-domain immunoglobulin (Nanobody), inhibits the interaction between ultralarge von Willebrand factor multimers and platelets. In this phase 2, controlled study, we randomly assigned patients with acquired TTP to subcutaneous caplacizumab (10 mg daily) or placebo during plasma exchange and for 30 days afterward. The primary end point was the time to a response, defined as confirmed normalization of the platelet count. Major secondary end points included exacerbations and relapses. RESULTS Seventy-five patients underwent randomization (36 were assigned to receive caplacizumab, and 39 to receive placebo). The time to a response was significantly reduced with caplacizumab as compared with placebo (39% reduction in median time, P = 0.005). Three patients in the caplacizumab group had an exacerbation, as compared with 11 patients in the placebo group. Eight patients in the caplacizumab group had a relapse in the first month after stopping the study drug, of whom 7 had ADAMTS13 activity that remained below 10%, suggesting unresolved autoimmune activity. Bleeding-related adverse events, most of which were mild to moderate in severity, were more common with caplacizumab than with placebo (54% of patients vs. 38%). The frequencies of other adverse events were similar in the two groups. Two patients in the placebo group died, as compared with none in the caplacizumab group. CONCLUSIONS Caplacizumab induced a faster resolution of the acute TTP episode than did placebo. The platelet-protective effect of caplacizumab was maintained during the treatment period. Caplacizumab was associated with an increased tendency toward bleeding, as compared with placebo. (Funded by Ablynx; ClinicalTrials. gov number, NCT01151423.)MASSACHUSETTS MEDICAL SOC2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/4707NEW ENGLAND JOURNAL OF MEDICINEISSN: 00284793ISSNe: 15334406reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p47072026-06-07T16:35:31Z
dc.title.none.fl_str_mv Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura
title Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura
spellingShingle Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura
Peyvandi, F
title_short Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura
title_full Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura
title_fullStr Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura
title_full_unstemmed Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura
title_sort Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura
dc.creator.none.fl_str_mv Peyvandi, F
Scully, M
Hovinga, JAK
Cataland, S
Knobl, P
Wu, HF
Artoni, A
Westwood, JP
Taleghani, MM
Jilma, B
Callewaert, F
Ulrichts, H
Duby, C
Tersago, D
TITAN Investigators
author Peyvandi, F
author_facet Peyvandi, F
Scully, M
Hovinga, JAK
Cataland, S
Knobl, P
Wu, HF
Artoni, A
Westwood, JP
Taleghani, MM
Jilma, B
Callewaert, F
Ulrichts, H
Duby, C
Tersago, D
TITAN Investigators
author_role author
author2 Scully, M
Hovinga, JAK
Cataland, S
Knobl, P
Wu, HF
Artoni, A
Westwood, JP
Taleghani, MM
Jilma, B
Callewaert, F
Ulrichts, H
Duby, C
Tersago, D
TITAN Investigators
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
description BACKGROUND Acquired thrombotic thrombocytopenic purpura (TTP) is caused by aggregation of platelets on ultralarge von Willebrand factor multimers. This microvascular thrombosis causes multiorgan ischemia with potentially life-threatening complications. Daily plasma exchange and immunosuppressive therapies induce remission, but mortality and morbidity due to microthrombosis remain high. METHODS Caplacizumab, an anti-von Willebrand factor humanized single-variable-domain immunoglobulin (Nanobody), inhibits the interaction between ultralarge von Willebrand factor multimers and platelets. In this phase 2, controlled study, we randomly assigned patients with acquired TTP to subcutaneous caplacizumab (10 mg daily) or placebo during plasma exchange and for 30 days afterward. The primary end point was the time to a response, defined as confirmed normalization of the platelet count. Major secondary end points included exacerbations and relapses. RESULTS Seventy-five patients underwent randomization (36 were assigned to receive caplacizumab, and 39 to receive placebo). The time to a response was significantly reduced with caplacizumab as compared with placebo (39% reduction in median time, P = 0.005). Three patients in the caplacizumab group had an exacerbation, as compared with 11 patients in the placebo group. Eight patients in the caplacizumab group had a relapse in the first month after stopping the study drug, of whom 7 had ADAMTS13 activity that remained below 10%, suggesting unresolved autoimmune activity. Bleeding-related adverse events, most of which were mild to moderate in severity, were more common with caplacizumab than with placebo (54% of patients vs. 38%). The frequencies of other adverse events were similar in the two groups. Two patients in the placebo group died, as compared with none in the caplacizumab group. CONCLUSIONS Caplacizumab induced a faster resolution of the acute TTP episode than did placebo. The platelet-protective effect of caplacizumab was maintained during the treatment period. Caplacizumab was associated with an increased tendency toward bleeding, as compared with placebo. (Funded by Ablynx; ClinicalTrials. gov number, NCT01151423.)
publishDate 2016
dc.date.none.fl_str_mv 2016
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://incliva.portalinvestigacion.com/publicaciones/4707
url https://incliva.portalinvestigacion.com/publicaciones/4707
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-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
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repository.mail.fl_str_mv
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