• Introduction

Primary immune thrombocytopenia (ITP) is classically associated with bleeding risk but also presents a relevant incidence of thromboembolic events (TEEs), particularly in patients with comorbidities. The use of thrombopoietin receptor agonists (TPO-RAs) has raised concerns regarding a potential increase in thrombotic risk, prompting multiple studies aimed at characterizing their safety profile. Among these agents, avatrombopag (AVA) remains less extensively studied in routine clinical settings. Most published meta-analyses to date combine data from randomized clinical trials and observational studies, which limits the ability to draw specific conclusions. While its clinical efficacy is generally well accepted, no systematic analysis has exclusively evaluated its performance exclusively in real-world settings. This study aimed to evaluate the safety profile, including the incidence of thromboembolic events, and clinical efficacy of AVA in adults with ITP through a meta-analysis focused solely on real-world studies.

  • Methods

A systematic review and meta-analysis were conducted in accordance with the PRISMA 2020 guidelines. Observational studies published since 2020 were included if they reported TEEs in adult patients with ITP treated with AVA and had a defined follow-up period. The databases consulted were PubMed/MEDLINE, Embase, Scopus, Google Scholar, and conference abstracts from ASH, EHA, and ISTH. Primary outcomes included thromboembolic complications, reported both as crude incidence and as events per 100 patient-years, and treatment response, defined as complete response (CR) when the platelet count (PC) was equal to or greater than 100 × 10⁹/L without the need for rescue therapy, and partial response (PR) when the PC was equal to or greater than 50 × 10⁹/L without rescue therapy. Secondary outcomes included time to response, treatment discontinuation, and adverse events (AE) related to AVA. Methodological quality was assessed using the ROBINS-I version 2 tool. Two independent reviewers performed study selection and quality assessment, with any discrepancies resolved through consensus. Statistical analysis was performed using random-effects models with R software version 4.4.1.

  • Results

A total of 58 records were identified through a comprehensive search strategy that combined biomedical databases and other relevant sources. After screening, 17 studies met the eligibility criteria and were included in the meta-analysis. Nine studies, comprising 763 patients, reported TEEs. The pooled proportion of patients experiencing at least one event during AVA treatment was 2.82% (95% CI: 1.61–4.27), with no heterogeneity (I² = 0.0%). The incidence rate, adjusted for exposure time, was 3.29 per 100 patient-years (95% CI: 1.81–5.08), with no heterogeneity.

Treatment response was assessed in ten studies. CR was assessed in 425 patients, yielding a pooled rate of 80.03% (95% CI: 72.94–86.35; I² = 62.3%). PR was evaluated in 629 patients across nine studies, with a pooled rate of 91.99% (95% CI: 89.25–94.41; I² = 11.3%).

Regarding secondary outcomes, time to response was reported in six studies; four used a threshold of ≥50 × 10⁹/L and two ≥30 × 10⁹/L. The pooled median was 11.1 days (95% CI: 8.2–13.9), with high heterogeneity (I² = 87.7%). The discontinuation rate, reported in twelve studies, was 18.86% (95% CI: 14.46–23.66; I² = 66.3%). AE related to AVA, reported in four studies, had a pooled incidence of 4.05% (95% CI: 1.58–7.43; I² = 55.7%) and an adjusted rate of 4.56 per 100 patient-years (95% CI: 1.47–8.90; I² = 60.1%).

  • Conclusions

This meta-analysis, focused exclusively on real-world evidence, reveals a low and consistent incidence of TEE in adult patients with ITP treated with AVA. These findings contrast positively with those reported in randomized clinical trials, supporting its vascular safety and use in routine clinical practice, even in populations with cardiovascular risk. In addition, the analysis confirms high rates of both complete and partial platelet response, along with favourable data on time to response, treatment discontinuation, and AE. Overall, these results reinforce the real-world safety and efficacy of AVA.

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2025
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