Comparison of the efficacy and safety of caplacizumab versus placebo in thrombotic thrombocytopenic purpura: a meta-analysis and systematic review based on randomized controlled trials

Abstract

Background: We conducted this meta-analysis to investigate the efficacy and safety of caplacizumab in patients with thrombotic thrombocytopenic purpura (TTP). TTP is a potentially fatal disorder characterized by systemic microvascular thrombosis.Methods: Randomized controlled trials (RCTs) were conducted from PubMed, Embase, Cochrane Library and Web of Science, China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases. RCTs of caplacizumab treatment for TPP were mainly included. Data from eligible studies were extracted and analyzed using relative effect sizes versus placebo use. The Cochrane bias assessment tool was used to assess the risk of bias of included studies, and the assessment results were presented graphically in Revman5.3.Results: Four RCTs with a total of 416 patients were included, all of which were of high quality.Caplacizumab was associated with improvements in platelet counts normalization time [weighted mean difference (WMD) −1.18, 95% confidence interval (CI): −2.55 to 0.19, I 2 =69.9%, P=0.036], plasma exchange (PE) time (WMD −2.97, 95% CI: −4.44 to −1.50, I 2 =8.2%, P=0.163) and hospital stay (WMD −2.88, 95% CI: −4.56 to −1.21, I 2 =48.7%, P=0.036). In addition, the occurrence of adverse events was also investigated.The difference in mortality between the two groups was not statistically significant [relative risk (RR) 0.56, 95% CI: 0.18 to 1.72, I 2 =22.7%, P=0.275], relapse (RR 0.68, 95% CI: 0.13 to 3.49, I 2 =78.3%, P=0.01), or major thrombotic events (RR 1.01, 95% CI: 0.65 to 1.57, I 2 =43.4%, P=0.151).Conclusions: Caplacizumab shortens the platelet normalization time, PE time, and hospital stay in patients with TTP, and did not significantly increase the risk of adverse events. These results indicate that caplacizumab treatment provides significant benefits to patients with TTP. Even though this is evidence from RCTs, few original studies were included, so more multicenter RCTs are required.

Efficacy and relative safety of caplacizumab in immune-mediated thrombotic thrombocytopenic purpura: a systematic review and meta-analysis

“…None of the studies showed a difference in death rates between the group caplacizumab and group placebo. In the same way, Djulbegovic et al and Chen et al found a similar conclusion that caplacizumab's reduction in death estimates was not significant [20,21].…”

Real-world Experience of Caplacizumab for Adolescents in the First-line Setting: Case Reports

“…Acquired thrombotic thrombocytopenic purpura (aTTP) is a thrombotic microangiopathy caused by severely reduced ADAMTS13 activity. 1,2 Usually, this is mediated by autoantibodies that target ADAMTS13, a protease responsible for cleaving von Willebrand factors (vWF). The absence of ADAMTS13 results in the circulation of ultralarge vWF multimers, which leads to thrombotic emergencies and a mortality rate up to 15% to 20%.…”

“…The absence of ADAMTS13 results in the circulation of ultralarge vWF multimers, which leads to thrombotic emergencies and a mortality rate up to 15% to 20%. 2,3 Caplacizumab is an anti-vWF monoclonal antibody approved in 2019 by the US Food and Drug Administration and European Medicines Agency for the treatment of aTTP in adults. It has demonstrated faster platelet normalization, clinical improvement, and reduced risk of recurrent or refractory disease.…”

“…Acquired thrombotic thrombocytopenic purpura (aTTP) is a thrombotic microangiopathy caused by severely reduced ADAMTS13 activity 1,2 . Usually, this is mediated by autoantibodies that target ADAMTS13, a protease responsible for cleaving von Willebrand factors (vWF).…”

“…Usually, this is mediated by autoantibodies that target ADAMTS13, a protease responsible for cleaving von Willebrand factors (vWF). The absence of ADAMTS13 results in the circulation of ultralarge vWF multimers, which leads to thrombotic emergencies and a mortality rate up to 15% to 20% 2,3 . Caplacizumab is an anti-vWF monoclonal antibody approved in 2019 by the US Food and Drug Administration and European Medicines Agency for the treatment of aTTP in adults.…”