Real-world safety and effectiveness of hetrombopag in patients with primary immune thrombocytopenia

Abstract Introduction: Primary Immune Thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder characterized by isolated thrombocytopenia without identifiable etiologies, resulting in decreased platelet counts (PLT) and increased bleeding risk. Management of ITP remains challenging, particularly for patients who are refractory or intolerant to first-line treatments such as corticosteroids or intravenous immunoglobulin (IVIg). Thrombopoietin receptor agonists (TPO-RAs) have emerged as an effective second-line options by stimulating platelet production. Hetrombopag is a novel oral, small-molecule, non-peptide TPO-RA approved in China for the treatment of chronic ITP. However, real-world data on its effectiveness in routine clinical practice is still insufficient. Here, we report preliminary findings from an observational study which aims to evaluate the safety and effectiveness of hetrombopag for ITP patients in real-world setting. Methods: In this multi-center, real-world study (ClinicalTrials.gov identifier: NCT05333861), patients with a confirmed diagnosis of ITP and baseline PLT <30×10⁹/L were included. As part of their routine medical care, patients would receive hetrombopag for the treatment of ITP, with the initial dose determined by the investigator based on the individual clinical conditions and subsequently adjusted according to PLT. Observational data were collected for all routine visits throughout the study period, including baseline characteristics, hetrombopag dosing, concomitant therapy, and longitudinal PLT. The outcome were safety and effectiveness; effectiveness, as reported here, was assessed by the change in PLT over time and the proportion of responders (PLT ≥30×10⁹/L). Results: As of April 16, 2025, 334 patients treated with hetrombopag for ITP were evaluable for analysis. The median age was 61 years (range 20–84), with the majority of female patients (59%). The median baseline PLT was 11.5 ×10⁹/L (range 1–29×10⁹/L). The median initial dose of hetrombopag was 5 mg/day, with 52% and 31% of patients starting at 5 mg/day and 7.5 mg/day, respectively. Regarding safety, no grade ≥3 AEs were reported, and no unexpected AEs were observed. As early as week 2 (first follow-up), the median PLT increased rapidly from 11.5×10⁹/L at baseline to 50×10⁹/L. By week 6 (second follow-up), it further rose to 56.5×10⁹/L. The median PLT peaked at 89×10⁹/L by week 12 (third follow-up) and remained elevated at 77×10⁹/L at week 24 (fifth follow-up), representing a sustained improvement compared with baseline. By week 2, 65% of patients responded (PLT ≥ 30×10⁹/L), and 49% exceeded >50×10⁹/L. These proportions increased slightly by week 6, reaching to 67% and 54%, respectively, and continued to rise by week 24 to 79% and 68%. Additionally, at treatment initiation, 13% of patients received concomitant therapy, primarily low-dose corticosteroids or recombinant human thrombopoietin (rhTPO). By week 24, only six patients remained on combination therapy (five with low-dose corticosteroids, one with rhTPO).Conclusions: Hetrombopag demonstrated favorable real-world safety and effectiveness in patients with ITP, leading to sustained improvements in platelet counts and reduced reliance on concomitant therapies. These findings provide meaningful evidence supporting the use of hetrombopag in routine clinical practice and underscore its potential as a core component in the long-term management of ITP.