Cargando…
Adding caplacizumab to standard of care in thrombotic thrombocytopenic purpura: a systematic review and meta-analysis
Immune thrombotic thrombocytopenic purpura (iTTP) is an acquired, fatal microangiopathy if untreated. Randomized controlled trials (RCTs) demonstrated faster time to response with addition of caplacizumab to standard of care (SOC). However, concerns about RCT selection bias and the high cost of capl...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society of Hematology
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196763/ https://www.ncbi.nlm.nih.gov/pubmed/36053773 http://dx.doi.org/10.1182/bloodadvances.2022008443 |
_version_ | 1785044414166466560 |
---|---|
author | Djulbegovic, Mia Tong, Jiayi Xu, Alice Yang, Joanna Chen, Yong Cuker, Adam Pishko, Allyson M. |
author_facet | Djulbegovic, Mia Tong, Jiayi Xu, Alice Yang, Joanna Chen, Yong Cuker, Adam Pishko, Allyson M. |
author_sort | Djulbegovic, Mia |
collection | PubMed |
description | Immune thrombotic thrombocytopenic purpura (iTTP) is an acquired, fatal microangiopathy if untreated. Randomized controlled trials (RCTs) demonstrated faster time to response with addition of caplacizumab to standard of care (SOC). However, concerns about RCT selection bias and the high cost of caplacizumab warrant examination of all evidence, including real-world observational studies. In this systematic review and meta-analysis, we searched for comparative studies evaluating SOC with or without caplacizumab for the treatment of iTTP. We assessed risk of bias using the Cochrane risk-of-bias-2 tool (RCTs) and the Newcastle-Ottawa Scale (observational studies). The primary efficacy and safety outcomes were all-cause mortality and treatment-emergent bleeding, respectively. Secondary outcomes included exacerbation and relapse, refractory iTTP, and time to response. We included 2 high-quality RCTs and 3 observational studies at high risk of bias comprising 632 total participants. Compared with SOC, caplacizumab was associated with a nonsignificant reduction in the relative risk [RR] of death in RCTs (RR, 0.21; 95% confidence interval [CI], 0.05-1.74) and observational studies (RR, 0.62; 95% CI, 0.07-4.41). Compared with SOC, caplacizumab was associated with an increased bleeding risk in RCTs (RR, 1.37; 95% CI, 1.06-1.77). In observational studies, bleeding risk was not significantly increased (RR, 7.10; 95% CI, 0.90-56.14). Addition of caplacizumab was associated with a significant reduction in refractory iTTP and exacerbation risks and shortened response time but increased relapse risk. Frontline addition of caplacizumab does not significantly reduce all-cause mortality compared with SOC alone, although it reduces refractory disease risk, shortens time to response, and improves exacerbation rates at the expense of increased relapse and bleeding risk. |
format | Online Article Text |
id | pubmed-10196763 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-101967632023-05-20 Adding caplacizumab to standard of care in thrombotic thrombocytopenic purpura: a systematic review and meta-analysis Djulbegovic, Mia Tong, Jiayi Xu, Alice Yang, Joanna Chen, Yong Cuker, Adam Pishko, Allyson M. Blood Adv Systematic Review Immune thrombotic thrombocytopenic purpura (iTTP) is an acquired, fatal microangiopathy if untreated. Randomized controlled trials (RCTs) demonstrated faster time to response with addition of caplacizumab to standard of care (SOC). However, concerns about RCT selection bias and the high cost of caplacizumab warrant examination of all evidence, including real-world observational studies. In this systematic review and meta-analysis, we searched for comparative studies evaluating SOC with or without caplacizumab for the treatment of iTTP. We assessed risk of bias using the Cochrane risk-of-bias-2 tool (RCTs) and the Newcastle-Ottawa Scale (observational studies). The primary efficacy and safety outcomes were all-cause mortality and treatment-emergent bleeding, respectively. Secondary outcomes included exacerbation and relapse, refractory iTTP, and time to response. We included 2 high-quality RCTs and 3 observational studies at high risk of bias comprising 632 total participants. Compared with SOC, caplacizumab was associated with a nonsignificant reduction in the relative risk [RR] of death in RCTs (RR, 0.21; 95% confidence interval [CI], 0.05-1.74) and observational studies (RR, 0.62; 95% CI, 0.07-4.41). Compared with SOC, caplacizumab was associated with an increased bleeding risk in RCTs (RR, 1.37; 95% CI, 1.06-1.77). In observational studies, bleeding risk was not significantly increased (RR, 7.10; 95% CI, 0.90-56.14). Addition of caplacizumab was associated with a significant reduction in refractory iTTP and exacerbation risks and shortened response time but increased relapse risk. Frontline addition of caplacizumab does not significantly reduce all-cause mortality compared with SOC alone, although it reduces refractory disease risk, shortens time to response, and improves exacerbation rates at the expense of increased relapse and bleeding risk. The American Society of Hematology 2022-09-05 /pmc/articles/PMC10196763/ /pubmed/36053773 http://dx.doi.org/10.1182/bloodadvances.2022008443 Text en © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Systematic Review Djulbegovic, Mia Tong, Jiayi Xu, Alice Yang, Joanna Chen, Yong Cuker, Adam Pishko, Allyson M. Adding caplacizumab to standard of care in thrombotic thrombocytopenic purpura: a systematic review and meta-analysis |
title | Adding caplacizumab to standard of care in thrombotic thrombocytopenic purpura: a systematic review and meta-analysis |
title_full | Adding caplacizumab to standard of care in thrombotic thrombocytopenic purpura: a systematic review and meta-analysis |
title_fullStr | Adding caplacizumab to standard of care in thrombotic thrombocytopenic purpura: a systematic review and meta-analysis |
title_full_unstemmed | Adding caplacizumab to standard of care in thrombotic thrombocytopenic purpura: a systematic review and meta-analysis |
title_short | Adding caplacizumab to standard of care in thrombotic thrombocytopenic purpura: a systematic review and meta-analysis |
title_sort | adding caplacizumab to standard of care in thrombotic thrombocytopenic purpura: a systematic review and meta-analysis |
topic | Systematic Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196763/ https://www.ncbi.nlm.nih.gov/pubmed/36053773 http://dx.doi.org/10.1182/bloodadvances.2022008443 |
work_keys_str_mv | AT djulbegovicmia addingcaplacizumabtostandardofcareinthromboticthrombocytopenicpurpuraasystematicreviewandmetaanalysis AT tongjiayi addingcaplacizumabtostandardofcareinthromboticthrombocytopenicpurpuraasystematicreviewandmetaanalysis AT xualice addingcaplacizumabtostandardofcareinthromboticthrombocytopenicpurpuraasystematicreviewandmetaanalysis AT yangjoanna addingcaplacizumabtostandardofcareinthromboticthrombocytopenicpurpuraasystematicreviewandmetaanalysis AT chenyong addingcaplacizumabtostandardofcareinthromboticthrombocytopenicpurpuraasystematicreviewandmetaanalysis AT cukeradam addingcaplacizumabtostandardofcareinthromboticthrombocytopenicpurpuraasystematicreviewandmetaanalysis AT pishkoallysonm addingcaplacizumabtostandardofcareinthromboticthrombocytopenicpurpuraasystematicreviewandmetaanalysis |