Long-term follow-up of patients treated with caplacizumab and safety and efficacy of repeat caplacizumab use: Post-HERCULES study.
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BORIS DOI
Publisher DOI
PubMed ID
36138517
Description
INTRODUCTION
Caplacizumab demonstrated efficacy and safety in patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) in the Phase 3 HERCULES trial. However, data on long-term outcomes following caplacizumab treatment are limited.
OBJECTIVES
The post-HERCULES trial (NCT02878603) evaluated long-term outcomes of patients with iTTP treated with caplacizumab in HERCULES and safety and efficacy of repeated caplacizumab use.
PATIENTS/METHODS
Over 3 years' follow-up, patients could receive open-label caplacizumab with therapeutic plasma exchange (TPE) and immunosuppressive therapy (IST) in case of recurrence. Adverse events (AEs) were assessed during the overall study period (intention-to-observe [ITO] population) and during recurrences (recurrence population). TTP-related events (TTP-related death, recurrence, major thromboembolic events) were assessed in the efficacy ITO population (patients without recurrence during HERCULES or before post-HERCULES).
RESULTS
Among 104 enrolled patients, incidences of AEs and serious AEs were similar between patients who had received caplacizumab+TPE+IST during HERCULES (n=75) and those treated with placebo+TPE+IST (placebo; n=29). TTP-related events occurred in 8% of patients (4/49) randomized to caplacizumab during HERCULES versus 38% (11/29) randomized to placebo. Nineteen patients had ≥1 recurrence; 13 of these were treated with caplacizumab. First recurrence episode was resolved or resolving for all patients treated with caplacizumab, including 9 patients with repeat caplacizumab use. All second recurrences (6/6) were resolved. Safety profile of caplacizumab for treatment of recurrence was consistent with HERCULES; most bleeding events were non-serious. No major cases of organ dysfunction were observed.
CONCLUSIONS
Long-term follow-up supports the safety and efficacy of caplacizumab for iTTP and its repeated use for recurrences.
Caplacizumab demonstrated efficacy and safety in patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) in the Phase 3 HERCULES trial. However, data on long-term outcomes following caplacizumab treatment are limited.
OBJECTIVES
The post-HERCULES trial (NCT02878603) evaluated long-term outcomes of patients with iTTP treated with caplacizumab in HERCULES and safety and efficacy of repeated caplacizumab use.
PATIENTS/METHODS
Over 3 years' follow-up, patients could receive open-label caplacizumab with therapeutic plasma exchange (TPE) and immunosuppressive therapy (IST) in case of recurrence. Adverse events (AEs) were assessed during the overall study period (intention-to-observe [ITO] population) and during recurrences (recurrence population). TTP-related events (TTP-related death, recurrence, major thromboembolic events) were assessed in the efficacy ITO population (patients without recurrence during HERCULES or before post-HERCULES).
RESULTS
Among 104 enrolled patients, incidences of AEs and serious AEs were similar between patients who had received caplacizumab+TPE+IST during HERCULES (n=75) and those treated with placebo+TPE+IST (placebo; n=29). TTP-related events occurred in 8% of patients (4/49) randomized to caplacizumab during HERCULES versus 38% (11/29) randomized to placebo. Nineteen patients had ≥1 recurrence; 13 of these were treated with caplacizumab. First recurrence episode was resolved or resolving for all patients treated with caplacizumab, including 9 patients with repeat caplacizumab use. All second recurrences (6/6) were resolved. Safety profile of caplacizumab for treatment of recurrence was consistent with HERCULES; most bleeding events were non-serious. No major cases of organ dysfunction were observed.
CONCLUSIONS
Long-term follow-up supports the safety and efficacy of caplacizumab for iTTP and its repeated use for recurrences.
Date of Publication
2022-12
Publication Type
Article
Subject(s)
600 - Technology::610 - Medicine & health
300 - Social sciences, sociology & anthropology::340 - Law
Keyword(s)
Blood platelets caplacizumab follow-up studies thrombotic thrombocytopenic purpura von Willebrand factor
Language(s)
en
Contributor(s)
Scully, Marie | |
de la Rubia, Javier | |
Pavenski, Katerina | |
Metjian, Ara | |
Knöbl, Paul | |
Peyvandi, Flora | |
Cataland, Spero | |
Coppo, Paul | |
Minkue Mi Edou, Jessica | |
De Passos Sousa, Rui | |
Callewaert, Filip | |
Gunawardena, Sriya | |
Lin, Julie |
Additional Credits
Universitätsklinik für Hämatologie und Hämatologisches Zentrallabor
Series
Journal of thrombosis and haemostasis
Publisher
Wiley-Blackwell
ISSN
1538-7836
Access(Rights)
open.access