Abstract
BACKGROUND: Caplacizumab, a nanobody targeting von Willebrand factor, has transformed the management of immune-mediated thrombotic thrombocytopenic purpura (iTTP) by rapidly restoring platelet counts and improving survival. However, comprehensive real-world evidence regarding its hematologic safety profile remains limited. METHODS: We conducted a post-marketing pharmacovigilance study using reports from the U.S. FDA Adverse Event Reporting System (FAERS) from 2019 to Q1 2025. Disproportionality analyses were performed using four signal-detection algorithms-reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS)-with false discovery rate adjustment. Time-to-onset was assessed among reports with available dates, and Weibull modeling was applied to characterize onset patterns. RESULTS: A total of 1,306 caplacizumab-related reports were identified, predominantly involving adult female patients with iTTP. Frequently reported adverse events included hematologic and hemorrhagic events (e.g., epistaxis and thrombocytopenia), as well as fatigue and laboratory abnormalities. Significant positive signals were consistently observed for bleeding-related preferred terms across multiple algorithms. The median time to onset was 10 days after treatment initiation, and Weibull modeling suggested an early-failure pattern, indicating greater susceptibility during the initial treatment cycles. CONCLUSIONS: In FAERS post-marketing data, caplacizumab-associated adverse events were mainly bleeding-related, generally predictable, and tended to occur early during therapy. Close clinical and laboratory monitoring-particularly of hematologic parameters-during the initial treatment period is warranted to balance bleeding vigilance with therapeutic efficacy. These findings provide real-world evidence to inform hematologists about the safety profile of caplacizumab in iTTP management.