Real-world clinical trial of hetrombopag (TPO-RA) in the treatment of primary immune thrombocytopenia (ITP)

Abstract Background: Primary immune Thrombocytopenia (ITP) is an acquired autoimmune hemorrhagic disorder characterized by isolated peripheral thrombocytopenia without identifiable causes. Its primary pathogenesis involves increased platelet destruction and reduced platelet production due to various humoral and cellular immune dysfunctions. Hetrombopag, a small-molecule non-peptide thrombopoietin receptor agonist (TPO-RA), promotes platelet production by activating downstream pathways (e.g., JAK/STAT) in megakaryocytes. Existing literature lacks real-world studies on the efficacy and safety of Hetrombopag in treating ITP patients across different disease phases. This study aimed to validate the real-world efficacy and safety of Hetrombopag in ITP treatment and explore its therapeutic benefits among patients with varying ITP stages. Methods: In this prospective clinical study, 167 patients were enrolled based on the following criteria: 1) Confirmed diagnosis of primary immune thrombocytopenia; 2) Baseline platelet count <30×10⁹/L. After enrollment, investigators determined the initial Hetrombopag dose and adjusted it according to platelet counts, targeting levels of 50–150×10⁹/L. Treatment continued until successful tapering and discontinuation, treatment failure, or other investigator-determined withdrawal criteria. The primary endpoint was the platelet response rate (platelet count≥30×10⁹/L) at Week 6. Secondary endpoints included platelet response rate (platelet count ≥30×10⁹/L) at Weeks 12, 16, and 24; and platelet response rate(platelet counts ≥100×10⁹/L) at Weeks 6 and 24; and incidence of adverse events (AEs). Results: As of April 14, 2025, 167 patients were enrolled. The median age was 47 years, with 66% females and median baseline platelet count of 9×10⁹/L. Median ITP duration was 12 months, including 53 newly diagnosed, 25 persistent, and 89 chronic ITP cases. WHO Bleeding Scale scores of 0 and 1 accounted for 44% and 55%, respectively. The median starting dose of Hetrombopag was 5 mg (range: 2.5–10 mg), with a median treatment duration of 9 months (range: 1–24 months). The primary endpoint is platelet response rate at Week 6 was 76%（121/160）. Secondary endpoints are platelet response rate(platelet count ≥30×10⁹/L) at Weeks 12, 16, and 24 were 78%(109/139) , 83%(96/115) , 88%(91/104) , and platelet response rate(platelet count ≥100×10⁹/L) at Weeks 6 and 24 were 31%(49/160) , 44%(46/104) , and No ≥Grade 3 hepatic dysfunction was observed during treatment. Platelet response rates (platelet count ≥30×10⁹/L) were analyzed by stratification according to disease stage, with the following results per subgroup:Newly diagnosed ITP patients: 80% (41/51) at Week 6, 76% (31/41) at Week 12, 87% (26/30) at Week 16, and 96% (26/27) at Week 24.Persistent ITP patients: 75% (18/24) at Week 6, 82% (18/22) at Week 12, 95% (18/19) at Week 16, and 94% (17/18) at Week 24.Chronic ITP patients: 73% (62/85) at Week 6, 79% (60/76) at Week 12, 79% (52/66) at Week 16, and 81% (48/59) at Week 24. Conclusion: This real-world study further validates the overall efficacy and favorable safety profile of Hetrombopag in ITP treatment. Consistent therapeutic benefits were observed across all ITP stages, indicating comparable efficacy in newly diagnosed, persistent, and chronic ITP patients.