Thromboembolic Risk of Thrombopoietin Receptor Agonists for Adult Primary Immune Thrombocytopenia: A Systematic...

Although randomized controlled trials (RCTs) have established evidence regarding thromboembolic risks of thrombopoietin receptor agonists (TPO-RAs) in immune thrombocytopenia (ITP) during short-term follow-up, the long-term risks remain uncertain. This meta-analysis integrates data from prospective studies and RCTs to provide a comprehensive evaluation of thromboembolic risks associated with TPO-RA therapy.

PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to January 23, 2025 for RCTs and prospective studies reporting thromboembolic events in patients treated with TPO-RAs. The primary outcome was the risk of any thromboembolism. Subgroup analyses separately assessed the incidence of venous and arterial thrombosis. Short-term (≤ 6 months) evidence was derived from RCTs, while long-term (6-12 months and > 12 months) evidence was supplemented by prospective studies. Data from RCTs were analyzed using the Peto odds ratio (OR) with 95% confidence intervals (CIs), and data from prospective studies were pooled to calculate the incidence of thromboembolic events.

The analysis included 12 RCTs (involving 1530 patients) and 11 prospective studies (involving 1820 patients). TPO-RAs significantly increased thromboembolic risk compared to placebo in the short-term (0.72% vs. 0.23%, Peto OR = 3.25, 95% CI = 1.11-9.51, p = 0.03). Pooled results from prospective studies demonstrated thromboembolism incidence of 3.84% at 6 to 12 months and 5.59% beyond 12 months of treatment with TPO-RAs. The reported incidence of arterial thrombosis increased from 0.14% (≤ 6 months) to 1.51% (6-12 months), and further to 4.2% (> 12 months). Whereas the reported incidence of venous thrombosis increased from 0.18% (≤ 6 months) to 2.50% (6-12 months), and plateaued at 2.55% beyond 12 months.

This analysis demonstrates that TPO-RAs therapy increases the risk of thromboembolism, with the risk of arterial events becoming particularly pronounced during long-term use. These findings highlight the need for individualized risk assessment and vigilant monitoring in patients receiving TPO-RAs.