Safety of non-peptide thrombopoietin receptor agonists in patients with immune thrombocytopenia: A systematic review and meta-analysis of short-term double-blind randomized clinical trials

The aim of the present study was to analyze the safety of non-peptide thrombopoietin receptor agonists (TPO-RAs) for immune thrombocytopenia (ITP) treatment. All studies reporting adverse events (AEs) in relation to ITP treatment with eltrombopag, avatrombopag, and hetrombopag were retrieved from PubMed, Web of Science, and Embase databases. RevMan 5.4.1 was used for meta-analysis, heterogeneity and bias analyses. A total of 1,078 patients from seven eligible studies were enrolled. In the enrolled clinical trials, the double-blind period was between 6 weeks and 6 months. The results revealed that the chances of any AEs [relative risk (RR)=1.16; 95% confidence interval (CI), 0.90-1.51; I-2=78%; P=0.26], grade 3/4 AEs (RR=1.07; 95% CI, 0.63-1.80; I-2=0%; P=0.81), elevated transaminase levels (RR=1.09; 95% CI, 0.68-1.74; I-2=0%; P=0.72), thrombosis (RR=1.92; 95% CI, 0.55-6.66; I-2=0%; P=0.31) and cataracts (RR=0.83; 95% CI, 0.38-1.83; I-2=0%; P=0.65) were not significantly higher in patients with ITP that received non-peptide TPO-RAs compared with patients with ITP treated with a placebo. The present study indicated that non-peptide TPO-RAs were relatively safe for patients with ITP, at least within 6 months of administration.