Impact of first-line use of caplacizumab on treatment outcomes in immune thrombotic thrombocytopenic purpura.

Humans Purpura, Thrombotic Thrombocytopenic Retrospective Studies Single-Domain Antibodies Purpura, Thrombocytopenic, Idiopathic Treatment Outcome Thrombosis ADAMTS13 Protein
ADAMTS13 protein observational study purpura thrombotic microangiopathies thrombotic thrombocytopenic von Willebrand factor

Journal

Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508

Informations de publication

Date de publication:
03 2023
Historique:
received: 01 07 2022
revised: 14 11 2022
accepted: 23 11 2022
pubmed: 26 1 2023
medline: 4 3 2023
entrez: 25 1 2023
Statut: ppublish

Résumé

The von Willebrand factor-directed nanobody caplacizumab has greatly changed the treatment of immune thrombotic thrombocytopenic purpura (iTTP) in recent years. Data from randomized controlled trials established efficacy and safety. This study aims to address open questions regarding patient selection, tailoring of therapy duration, obstacles in prescribing caplacizumab in iTTP, effect on adjunct treatment, and outcomes in the real-world setting. We report retrospective, observational cohorts of 113 iTTP episodes treated with caplacizumab and 119 historical control episodes treated without caplacizumab. We aggregated data from the caplacizumab phase II/III trials and real-world data from France, the United Kingdom, Germany, and Austria (846 episodes, 396 treated with caplacizumab, and 450 historical controls). Caplacizumab was efficacious in iTTP, independent of the timing of therapy initiation, but curtailed the time of active iTTP only when used in the first-line therapy within 72 hours after diagnosis and until at least partial ADAMTS13-activity remission. Aggregated data from multiple study populations showed that caplacizumab use resulted in significant absolute risk reduction of 2.87% for iTTP-related mortality (number needed to treat 35) and a relative risk reduction of 59%. Caplacizumab should be used in first line and until ADAMTS13-remission, lowers iTTP-related mortality and refractoriness, and decreases the number of daily plasma exchange and hospital stay. This trial is registered at www. gov as #NCT04985318.

Sections du résumé

BACKGROUND
The von Willebrand factor-directed nanobody caplacizumab has greatly changed the treatment of immune thrombotic thrombocytopenic purpura (iTTP) in recent years. Data from randomized controlled trials established efficacy and safety.
OBJECTIVES
This study aims to address open questions regarding patient selection, tailoring of therapy duration, obstacles in prescribing caplacizumab in iTTP, effect on adjunct treatment, and outcomes in the real-world setting.
METHODS
We report retrospective, observational cohorts of 113 iTTP episodes treated with caplacizumab and 119 historical control episodes treated without caplacizumab. We aggregated data from the caplacizumab phase II/III trials and real-world data from France, the United Kingdom, Germany, and Austria (846 episodes, 396 treated with caplacizumab, and 450 historical controls).
RESULTS
Caplacizumab was efficacious in iTTP, independent of the timing of therapy initiation, but curtailed the time of active iTTP only when used in the first-line therapy within 72 hours after diagnosis and until at least partial ADAMTS13-activity remission. Aggregated data from multiple study populations showed that caplacizumab use resulted in significant absolute risk reduction of 2.87% for iTTP-related mortality (number needed to treat 35) and a relative risk reduction of 59%.
CONCLUSION
Caplacizumab should be used in first line and until ADAMTS13-remission, lowers iTTP-related mortality and refractoriness, and decreases the number of daily plasma exchange and hospital stay. This trial is registered at www.
CLINICALTRIALS
gov as #NCT04985318.

Identifiants

DOI: 10.1016/j.jtha.2022.11.010 PMID: 36696206
pubmed: 36696206
pii: S1538-7836(22)07624-3
doi: 10.1016/j.jtha.2022.11.010
pii:
doi:

Substances chimiques

caplacizumab 2R27AB6766
Single-Domain Antibodies 0
ADAMTS13 Protein EC 3.4.24.87

Banques de données

ClinicalTrials.gov
['NCT04985318']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

559-572

Investigateurs

Fedai Özcan (F)
Silke Markau (S)
Matthias Girndt (M)
Helmut Felten (H)
Martin Hausberg (M)
Marcus Brand (M)
Jens Gerth (J)
Martin Bommer (M)
Stefan Zschiedrich (S)
Johanna Schneider (J)
Saban Elitok (S)
Alexander Gawlik (A)
Vedat Schwenger (V)
Maximilian Roeder (M)
Jörg Radermacher (J)
Anke Morgner (A)
Regina Herbst (R)
Charis von Auer (C)

Informations de copyright

Copyright © 2022 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interests L.A.V. received speaker honoraria and consultant fees from Sanofi-Genzyme and AstraZeneca. J.K. reports speaker honoraria and participation on advisory boards from Alexion, Sanofi, and Chiesi. W.M. reports grants from Takeda/Shire and CSL Behring and received speaker honoraria and consultant fees from Takeda/Shire and CSL Behring. P.T.B. received speaker honoraria and consultant fees from Sanofi-Genzyme, AstraZeneca, Alexion, Bayer, Travere, Pfizer, Novartis, Roche, and participated in advisory boards for Alexion, Sanofi-Genzyme, Novartis, Travere, and Bayer. He declares research funding from the German Research Foundation BR-2955/8. R.W. received speaker honoraria and consultant fees from Sanofi-Genzyme. He additionally declares research funding from the German Federal Ministry of Education and Research and the German Federal Ministry of Health. U.S. reports study fees and/or consultancy/advisory board fees from Chemocentryx/Vifor, Ablynx/Genzyme-Sanofi, Alexion, Travere, Alynlam Pharmaceuticals, and Allena Pharmaceuticals. J.M. received speaker honoraria and consultant fees from Ablynx, Alexion, and Sanofi-Genzyme. D.A.Eichenhauer has received speaker honoraria from Sanofi-Genzyme and Takeda. K.S. has received speaker honoraria from AbbVie, Merck, Pfizer, and Roche, consultant fees from AbbVie, Amgen, Bristol-Myers Squibb, Merck, Novartis, and Roche, and travel and congress fee compensation from AbbVie, Bristol-Myers Squibb, Celgene, Janssen Cilag, Lilly, and Servier. M.H. reports travel and congress fee compensation and speaker honoraria from Jazz Pharmaceuticals. P.K. reports travel support, participation in data safety monitoring boards and advisory boards, and consulting fees and/or speaker honoraria from Ablynx/Sanofi, Shire Roche, Novo Nordisk, CSL-Behring, and Biotest. F.B. reports speaker honoraria and consulting fees from Sanofi-Genzyme. A.G. reports consulting fees from Sanofi-Genzyme and Alexion and participation in advisory boards for Alexion. T.M. reports speaker honoraria from Sanofi-Aventis Deutschland GmbH. A.S. reports advisory board fees from Sanofi-Genzyme. K.S. reports speaker honoraria from AstraZeneca, Novartis, Takeda/Shire, and Vifor. M. K. reports speaker honoraria from Sanofi-Genzyme. All other authors report no conflict of interest.

Auteurs

Linus A Völker (LA)

Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Cologne Cluster of Excellence on Cellular Stress Responses in Ageing-Associated Diseases, Cologne, Germany.

Jessica Kaufeld (J)

Department of Nephrology and Hypertension, Medical School Hannover, Hannover, Germany.

Gesa Balduin (G)

Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Lena Merkel (L)

Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Lucas Kühne (L)

Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Dennis A Eichenauer (DA)

First Department of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf, University of Cologne, Cologne, Germany.

Thomas Osterholt (T)

Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Holger Hägele (H)

Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Martin Kann (M)

Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Cologne Cluster of Excellence on Cellular Stress Responses in Ageing-Associated Diseases, Cologne, Germany.

Franziska Grundmann (F)

Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

Benedikt Kolbrink (B)

Department of Nephrology and Hypertension, University Hospital Schleswig-Holstein, Kiel, Germany.

Kevin Schulte (K)

Department of Nephrology and Hypertension, University Hospital Schleswig-Holstein, Kiel, Germany.

Anja Gäckler (A)

Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Andreas Kribben (A)

Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Kristina Boss (K)

Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Sebastian A Potthoff (SA)

University Hospital Düsseldorf, Department of Nephrology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany, Germany.

Lars C Rump (LC)

University Hospital Düsseldorf, Department of Nephrology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany, Germany.

Tilman Schmidt (T)

Department of Medicine, University Medical Center Hamburg-Eppendorf, Germany.

Anja S Mühlfeld (AS)

Uniklinik RWTH Aachen, Department of Medicine, Division of Nephrology, Aachen, Germany.

Karsten Schulmann (K)

Klinik für Hämatologie, Onkologie Palliativmedizin und Stammzelltransplantation, Klinikum Hochsauerland GmbH, Walburga Krankenhaus Meschede, Meschede, Germany; MVZ Hochsauerland GmbH, Praxis für Hämatologie und Onkologie, Arnsberg, Germany.

Matthias Hermann (M)

Medizinische Klinik V, Hämatologie/Onkologie, Sozialstiftung Bamberg, Klinikum am Bruderwald, Bamberg.

Jens Gaedeke (J)

Department of Nephrology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.

Kristin Sauerland (K)

Klinik für Innere Medizin, Hämatologie/Onkologie, Stammzelltransplantation und Palliativmedizin, Johannesstift, Bielefeld, Germany.

Jörn Bramstedt (J)

Medizinische Klinik II Sektion Nephrologie, Klinikum Bremerhaven Reinkenheide, Bremerhaven, Germany.

Ulrich P Hinkel (UP)

Klinik für Nephrologie, Zentralklinik Bad Berka GmbH, Bad Berka, Germany.

Wolfgang Miesbach (W)

Department of Hemostaseology-Hemophilia Center, University Hospital Frankfurt, Frankfurt, Germany.

Frederic Bauer (F)

Medical Department I, Marien Hospital Herne, Ruhr-University Bochum, Germany.

Timm H Westhoff (TH)

Medical Department I, Marien Hospital Herne, Ruhr-University Bochum, Germany.

Heike Bruck (H)

Medical Clinic III, Helios Hospital Krefeld, Krefeld, Germany.

Veronika Buxhofer-Ausch (V)

Department of Internal Medicine I with Hematology, Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz Elisabethinen, Linz, Austria; Medical Faculty, Johannes Kepler University Linz, Linz, Austria.

Tobias J Müller (TJ)

Department of Neurology, University Hospital Ruppin-Brandenburg, Brandenburg Medical School, Neuruppin, Germany.

Ralph Wendt (R)

Department of Infectious Diseases/Tropical Medicine, Nephrology/KfH Renal Unit and Rheumatology, St. Georg Hospital Leipzig, Germany.

Ana Harth (A)

Department of Nephrology, Transplantation, and Medical Intensive Care, University Witten/Herdecke, Medical Centre Cologne-Merheim, Cologne, Germany.

Adrian Schreiber (A)

Department of Nephrology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany; Experimental and Clinical Research Center, Charité, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.

Evelyn Seelow (E)

Department of Nephrology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany; Experimental and Clinical Research Center, Charité, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.

Markus Tölle (M)

Charité-Universitätsmedizin Berlin, Cooperate Member of Freie Universität and Humboldt Universität, Department of Nephrology and Medical Intensive Care, Berlin, Germany.

Christopher Gohlisch (C)

Charité-Universitätsmedizin Berlin, Cooperate Member of Freie Universität and Humboldt Universität, Department of Nephrology and Medical Intensive Care, Berlin, Germany.

Markus Bieringer (M)

Department of Cardiology and Nephrology, Helios Klinik Berlin-Buch, Berlin, Germany.

Gesa Geuther (G)

Nordbadpraxis München-Praxis für Innere Medizin, Schwerpunktpraxis für Hämatologie, Onkologie, HIV und Palliativmedizin, München, Germany.

Wolfram J Jabs (WJ)

Department of Nephrology, Vivantes Klinikum im Friedrichshain, Berlin, Germany.

Michael Fischereder (M)

Nephrology Division, Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany.

Anke von Bergwelt-Baildon (A)

Nephrology Division, Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany.

Ulf Schönermarck (U)

Nephrology Division, Department of Medicine IV, University Hospital, LMU Munich, Munich, Germany.

Paul Knoebl (P)

Division of Hematology and Hemostasis, Department of Medicine 1, Medical University of Vienna, Vienna, Austria.

Jan Menne (J)

KRH Klinikum Mitte-Location Siloah, Hannover, Germany.

Paul T Brinkkoetter (PT)

Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Cologne Cluster of Excellence on Cellular Stress Responses in Ageing-Associated Diseases, Cologne, Germany. Electronic address: paul.brinkkoetter@uk-koeln.de.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Impact of first-line use of caplacizumab on...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations cutanées › Purpura › Purpura thrombopénique › Purpura thrombotique thrombocytopénique › Impact of first-line use of caplacizumab on...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études rétrospectives › Impact of first-line use of caplacizumab on...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Fragments d'immunoglobuline › Fragments Fab d'immunoglobuline › Anticorps à domaine unique › Impact of first-line use of caplacizumab on...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Manifestations cutanées › Purpura › Purpura thrombopénique › Purpura thrombopénique idiopathique › Impact of first-line use of caplacizumab on...
questionsmedicales.fr › Qualité, accès, évaluation des soins de santé › Qualité des soins de santé › Mécanismes d'évaluation des soins de santé › Évaluation des résultats et des processus en soins de santé › Évaluation de résultat (soins) › Résultat thérapeutique › Impact of first-line use of caplacizumab on...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Embolie et thrombose › Thrombose › Impact of first-line use of caplacizumab on...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Protéines ADAMTS › Protéine ADAMTS13 › Impact of first-line use of caplacizumab on...