Response to Hetrombopag Among patients with acute and persistent primary immune thrombocytopenia: A real-world study in China

Abstract Background: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet counts (PC), which increases the risk of severe bleeding events in patients. ITP can be classified into acute ( 3 months) and persistent (3-12 months) based on the course of the disease. Thrombopoietin receptor agonist (TPO-RA) therapy aims to elevate PC to a target threshold level, thereby minimizing bleeding risk. Hetrombopag (HET), as a new TPO-RA agent, was approved in China in 2021 for the treatment of chronic ITP in adults. However, real-world data have demonstrated its efficacy in acute and persistent ITP. In this study, we report the treatment outcomes of acute and persistent ITP patients treated with HET in real-world clinical practice. Objective: To describe the response to HET in patients with acute and persistent ITP. Methods: The study included patients who initiated HET treatment between January 2022 and February 2025. The index date was defined as the start date of HET, and the follow-up period is from the start date to the end of data availability or the end of the study. Patients with a disease duration of less than 3 months who received HET treatment were classified into the acute ITP group. Those receiving HET treatment for 3-12 months were categorized as the persistent ITP group. Therapeutic effect evaluation: 1. Complete response (CR): Platelet count ≥100×109/L after treatment and no bleeding manifestations. 2. Effective (R): After treatment, the platelet count was ≥30×109/L, which was at least twice the basal platelet count, and there was no bleeding manifestation. 3. Ineffective (NR): After treatment, the platelet count is less than 30×109/L, or the increase in platelet count is less than twice the baseline value, or there is bleeding. Results: A total of 34 patients were enrolled, including 16 (47%) with acute ITP and 18 (53%) with persistent ITP. The median age was 57 years (30–69) in the acute ITP group and 50 years (20–73) in the persistent ITP group. The male-to-female ratio was 3:13 in the acute group and 2:16 in the persistent group. The median follow-up time was 15.5 months (4-23) in the acute ITP group and 7.5 months (1-25) in the persistent ITP group. In the acute ITP group, the initial dose of HET were 2.5 mg/day (n=3), 5 mg/day (n=9), and 7.5 mg/day (n=4). In the persistent ITP group, starting doses were 2.5 mg/day (n=2), 5 mg/day (n=15), and 7.5 mg/day (n=1). All acute ITP patients had prior steroid exposure, with 2 receiving concurrent HET + steroids. Persistent ITP patients had received steroids within the first 3 months but were switched to HET monotherapy thereafter. The mean baseline platelet count was (19.81±17.67) ×10⁹/L in the acute group and (19.22±11.61) ×10⁹/L in the persistent group. The median time to response was 10.5 days (7-42) in the acute ITP group and 14.0 days (6-48) in the persistent ITP group (p0.05). The ORR(CR+PR) rates at 1, 2, 4, 8, and 12 weeks in the acute ITP group were 66.67%, 71.43%, 81.25%, 93.75%, and 93.33%, respectively, with corresponding CR rates of 25.00%, 42.86%, 43.75%, 75.00%, and 66.67%. In contrast, the persistent ITP group had ORR rates of 57.14%, 61.54%, 75.00%, 75.00%, and 81.82% at the same time points, with CR rates of 14.29%, 30.77%, 50.00%, 41.67%, and 36.36%, respectively. These results indicate that the therapeutic efficacy was better in the acute ITP group than in the persistent ITP group. Mean platelet counts at weeks 1, 2, 4, 8, and 12 were: Acute ITP group:(80.92±82.14) ×10⁹/L, (105.71±87.61) ×10⁹/L, (113.31±80.82) ×10⁹/L, (117.25±50.64) ×10⁹/L, and (148.8±84.46) ×10⁹/L ×10⁹/L. Persistent ITP group: (50.43±30.40) ×10⁹/L, (93.69±133.97) ×10⁹/L, (111.69±98.71) ×10⁹/L, (107.83±86.09) ×10⁹/L, and (87.27±53.39) ×10⁹/L. No severe adverse events were observed; mild headache occurred in 1 patient and liver injury in 1 patient. Conclusions: Most patients with acute and persistent ITP achieved a treatment response with hetrombopag therapy. Acute ITP patients showed better therapeutic outcomes when treated with hetrombopag. The average platelet count increased with prolonged treatment duration.