Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura

F. Peyvandi, M. Scully, J. A. Kremer Hovinga, P. Knöbl, S. Cataland, K. De Beuf, F. Callewaert, H. De Winter, R. K. Zeldin

Research output: Contribution to journalArticle

Abstract

Essentials Acquired thrombotic thrombocytopenic purpura (aTTP) is linked with significant morbidity/mortality. Caplacizumab's effect on major thromboembolic (TE) events, exacerbations and death was studied. Fewer caplacizumab-treated patients had a major TE event, an exacerbation, or died versus placebo. Caplacizumab has the potential to reduce the acute morbidity and mortality associated with aTTP. Summary: Background Acquired thrombotic thrombocytopenic purpura (aTTP) is a life-threatening autoimmune thrombotic microangiopathy. In spite of treatment with plasma exchange and immunosuppression, patients remain at risk for thrombotic complications, exacerbations, and death. In the phase II TITAN study, treatment with caplacizumab, an anti-von Willebrand factor Nanobody® was shown to reduce the time to confirmed platelet count normalization and exacerbations during treatment. Objective The clinical benefit of caplacizumab was further investigated in a post hoc analysis of the incidence of major thromboembolic events and exacerbations during the study drug treatment period and thrombotic thrombocytopenic purpura-related death during the study. Methods The Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) for ‘embolic and thrombotic events’ was run to investigate the occurrence of major thromboembolic events and exacerbations in the safety population of the TITAN study, which consisted of 72 patients, of whom 35 received caplacizumab and 37 received placebo. Results Four events (one pulmonary embolism and three aTTP exacerbations) were reported in four patients in the caplacizumab group, and 20 such events were reported in 14 patients in the placebo group (two acute myocardial infarctions, one ischemic stroke, one hemorrhagic stroke, one pulmonary embolism, one deep vein thrombosis, one venous thrombosis, and 13 aTTP exacerbations). Two of the placebo-treated patients died from aTTP during the study. Conclusion In total, 11.4% of caplacizumab-treated patients and 43.2% of placebo-treated patients experienced one or more major thromboembolic events, experienced an exacerbation, or died. This analysis shows the potential for caplacizumab to reduce the risk of major thromboembolic morbidities and mortality associated with aTTP.

Original languageEnglish
Pages (from-to)1448-1452
Number of pages5
JournalJournal of Thrombosis and Haemostasis
Volume15
Issue number7
DOIs
Publication statusPublished - Jul 1 2017

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Placebos
Morbidity
Pulmonary Embolism
Venous Thrombosis
Mortality
Medical Dictionaries
Single-Domain Antibodies
Stroke
Thrombotic Microangiopathies
Acquired Thrombotic thrombocytopenic purpura
caplacizumab
Thrombotic Thrombocytopenic Purpura
Plasma Exchange
von Willebrand Factor
Therapeutics
Platelet Count
Immunosuppression
Myocardial Infarction
Safety
Incidence

Keywords

  • caplacizumab
  • morbidity
  • mortality
  • purpura, thrombotic thrombocytopenic
  • von Willebrand factor

ASJC Scopus subject areas

  • Hematology

Cite this

Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura. / Peyvandi, F.; Scully, M.; Kremer Hovinga, J. A.; Knöbl, P.; Cataland, S.; De Beuf, K.; Callewaert, F.; De Winter, H.; Zeldin, R. K.

In: Journal of Thrombosis and Haemostasis, Vol. 15, No. 7, 01.07.2017, p. 1448-1452.

Research output: Contribution to journalArticle

Peyvandi, F. ; Scully, M. ; Kremer Hovinga, J. A. ; Knöbl, P. ; Cataland, S. ; De Beuf, K. ; Callewaert, F. ; De Winter, H. ; Zeldin, R. K. / Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura. In: Journal of Thrombosis and Haemostasis. 2017 ; Vol. 15, No. 7. pp. 1448-1452.
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abstract = "Essentials Acquired thrombotic thrombocytopenic purpura (aTTP) is linked with significant morbidity/mortality. Caplacizumab's effect on major thromboembolic (TE) events, exacerbations and death was studied. Fewer caplacizumab-treated patients had a major TE event, an exacerbation, or died versus placebo. Caplacizumab has the potential to reduce the acute morbidity and mortality associated with aTTP. Summary: Background Acquired thrombotic thrombocytopenic purpura (aTTP) is a life-threatening autoimmune thrombotic microangiopathy. In spite of treatment with plasma exchange and immunosuppression, patients remain at risk for thrombotic complications, exacerbations, and death. In the phase II TITAN study, treatment with caplacizumab, an anti-von Willebrand factor Nanobody{\circledR} was shown to reduce the time to confirmed platelet count normalization and exacerbations during treatment. Objective The clinical benefit of caplacizumab was further investigated in a post hoc analysis of the incidence of major thromboembolic events and exacerbations during the study drug treatment period and thrombotic thrombocytopenic purpura-related death during the study. Methods The Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) for ‘embolic and thrombotic events’ was run to investigate the occurrence of major thromboembolic events and exacerbations in the safety population of the TITAN study, which consisted of 72 patients, of whom 35 received caplacizumab and 37 received placebo. Results Four events (one pulmonary embolism and three aTTP exacerbations) were reported in four patients in the caplacizumab group, and 20 such events were reported in 14 patients in the placebo group (two acute myocardial infarctions, one ischemic stroke, one hemorrhagic stroke, one pulmonary embolism, one deep vein thrombosis, one venous thrombosis, and 13 aTTP exacerbations). Two of the placebo-treated patients died from aTTP during the study. Conclusion In total, 11.4{\%} of caplacizumab-treated patients and 43.2{\%} of placebo-treated patients experienced one or more major thromboembolic events, experienced an exacerbation, or died. This analysis shows the potential for caplacizumab to reduce the risk of major thromboembolic morbidities and mortality associated with aTTP.",
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T1 - Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura

AU - Peyvandi, F.

AU - Scully, M.

AU - Kremer Hovinga, J. A.

AU - Knöbl, P.

AU - Cataland, S.

AU - De Beuf, K.

AU - Callewaert, F.

AU - De Winter, H.

AU - Zeldin, R. K.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Essentials Acquired thrombotic thrombocytopenic purpura (aTTP) is linked with significant morbidity/mortality. Caplacizumab's effect on major thromboembolic (TE) events, exacerbations and death was studied. Fewer caplacizumab-treated patients had a major TE event, an exacerbation, or died versus placebo. Caplacizumab has the potential to reduce the acute morbidity and mortality associated with aTTP. Summary: Background Acquired thrombotic thrombocytopenic purpura (aTTP) is a life-threatening autoimmune thrombotic microangiopathy. In spite of treatment with plasma exchange and immunosuppression, patients remain at risk for thrombotic complications, exacerbations, and death. In the phase II TITAN study, treatment with caplacizumab, an anti-von Willebrand factor Nanobody® was shown to reduce the time to confirmed platelet count normalization and exacerbations during treatment. Objective The clinical benefit of caplacizumab was further investigated in a post hoc analysis of the incidence of major thromboembolic events and exacerbations during the study drug treatment period and thrombotic thrombocytopenic purpura-related death during the study. Methods The Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) for ‘embolic and thrombotic events’ was run to investigate the occurrence of major thromboembolic events and exacerbations in the safety population of the TITAN study, which consisted of 72 patients, of whom 35 received caplacizumab and 37 received placebo. Results Four events (one pulmonary embolism and three aTTP exacerbations) were reported in four patients in the caplacizumab group, and 20 such events were reported in 14 patients in the placebo group (two acute myocardial infarctions, one ischemic stroke, one hemorrhagic stroke, one pulmonary embolism, one deep vein thrombosis, one venous thrombosis, and 13 aTTP exacerbations). Two of the placebo-treated patients died from aTTP during the study. Conclusion In total, 11.4% of caplacizumab-treated patients and 43.2% of placebo-treated patients experienced one or more major thromboembolic events, experienced an exacerbation, or died. This analysis shows the potential for caplacizumab to reduce the risk of major thromboembolic morbidities and mortality associated with aTTP.

AB - Essentials Acquired thrombotic thrombocytopenic purpura (aTTP) is linked with significant morbidity/mortality. Caplacizumab's effect on major thromboembolic (TE) events, exacerbations and death was studied. Fewer caplacizumab-treated patients had a major TE event, an exacerbation, or died versus placebo. Caplacizumab has the potential to reduce the acute morbidity and mortality associated with aTTP. Summary: Background Acquired thrombotic thrombocytopenic purpura (aTTP) is a life-threatening autoimmune thrombotic microangiopathy. In spite of treatment with plasma exchange and immunosuppression, patients remain at risk for thrombotic complications, exacerbations, and death. In the phase II TITAN study, treatment with caplacizumab, an anti-von Willebrand factor Nanobody® was shown to reduce the time to confirmed platelet count normalization and exacerbations during treatment. Objective The clinical benefit of caplacizumab was further investigated in a post hoc analysis of the incidence of major thromboembolic events and exacerbations during the study drug treatment period and thrombotic thrombocytopenic purpura-related death during the study. Methods The Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) for ‘embolic and thrombotic events’ was run to investigate the occurrence of major thromboembolic events and exacerbations in the safety population of the TITAN study, which consisted of 72 patients, of whom 35 received caplacizumab and 37 received placebo. Results Four events (one pulmonary embolism and three aTTP exacerbations) were reported in four patients in the caplacizumab group, and 20 such events were reported in 14 patients in the placebo group (two acute myocardial infarctions, one ischemic stroke, one hemorrhagic stroke, one pulmonary embolism, one deep vein thrombosis, one venous thrombosis, and 13 aTTP exacerbations). Two of the placebo-treated patients died from aTTP during the study. Conclusion In total, 11.4% of caplacizumab-treated patients and 43.2% of placebo-treated patients experienced one or more major thromboembolic events, experienced an exacerbation, or died. This analysis shows the potential for caplacizumab to reduce the risk of major thromboembolic morbidities and mortality associated with aTTP.

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