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
Date of Publication
December 2022
Publication Type
Article
Division/Institute
Contributor
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 |
Series
Journal of thrombosis and haemostasis
ISSN or ISBN (if monograph)
1538-7836
Publisher
Wiley-Blackwell
Language
English
Publisher DOI
PubMed ID
36138517
Uncontrolled Keywords
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.
File(s)
| File | File Type | Format | Size | License | Publisher/Copright statement | Content | |
|---|---|---|---|---|---|---|---|
| J_of_Thrombosis_Haemost_-_2022_-_Scully_-_Long_term_follow_up_of_patients_treated_with_caplacizumab_and_safety_and_efficacy.pdf | text | Adobe PDF | 2.32 MB | accepted |