Real-world experience with caplacizumab in the management of acute TTP.

Abstract

The cornerstone of life-saving therapy in immune-mediated thrombotic thrombocytopenic purpura (iTTP) has been plasma exchange (PEX) combined with immunomodulatory strategies. Caplacizumab, a novel anti-von Willebrand factor nanobody trialed in 2 multicenter randomized controlled trials (RCTs) leading to European Union and US Food and Drug Administration approval, has been available in the United Kingdom (UK) through a patient access scheme. Data were collected retrospectively from 2018 to 2020 for 85 patients (4 children) receiving caplacizumab from 22 UK hospitals. Patient characteristics and outcomes in the real-world clinical setting were compared with caplacizumab trial end points and historical outcomes in the precaplacizumab era. Eighty-four of 85 patients received steroid and rituximab alongside PEX; 26% required intubation. Median time to platelet count normalization (3 days), duration of PEX (7 days), and hospital stay (12 days) were comparable with RCT data. Median duration of PEX and time from PEX initiation to platelet count normalization were favorable compared with historical outcomes (P < .05). Thrombotic thrombocytopenic purpura (TTP) recurred in 5 of 85 patients; all had persistent ADAMTS13 activity < 5 IU/dL. Of 31 adverse events in 26 patients, 17 of 31 (55%) were bleeding episodes, and 5 of 31 (16%) were thrombotic events (2 unrelated to caplacizumab); mortality was 6% (5/85), with no deaths attributed to caplacizumab. In 4 of 5 deaths, caplacizumab was introduced >48 hours after PEX initiation (3-21 days). This real-world evidence represents the first and largest series of TTP patients, including pediatric patients, receiving caplacizumab outside of clinical trials. Representative of true clinical practice, the findings provide valuable information for clinicians treating TTP globally.

• Authors: Tina Dutt, Rebecca J Shaw, Matthew Stubbs, Jun Yong, Benjamin Bailiff, Tanya Cranfield, Maeve P Crowley, Michael Desborough, Toby A Eyre, Richard Gooding, John Grainger, John Hanley, Joanna Haughton, Joannes Hermans, Quentin Hill, Louise Humphrey, Gillian Lowe, Hamish Lyall, Muhammad Mohsin, Phillip L R Nicolson, Nicole Priddee, Alexandros Rampotas, Rachel Rayment, Susan Rhodes, Alice Taylor, William Thomas, Oliver Tomkins, Joost J Van Veen, Steven Lane, Cheng-Hock Toh, Marie Scully
• Journal: Blood (Blood) Vol. 137 Issue 13 Pg. 1731-1740 (04 01 2021) ISSN: 1528-0020 [Electronic] United States
• PMID: 33150355 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © 2021 by The American Society of Hematology.

Chemical References

• Fibrinolytic Agents
• Single-Domain Antibodies
• von Willebrand Factor
• caplacizumab

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Child
• Child, Preschool
• Disease Management
• Female
• Fibrinolytic Agents (adverse effects, therapeutic use)
• Humans
• Male
• Middle Aged
• Purpura, Thrombotic Thrombocytopenic (drug therapy, epidemiology)
• Single-Domain Antibodies (adverse effects, therapeutic use)
• Treatment Outcome
• United Kingdom (epidemiology)
• Young Adult
• von Willebrand Factor (antagonists & inhibitors)