Efficacy and Safety Study of Switching from Hetrombopag or Eltrombopag to Avatrombopag in Childhood ITP

Background: Primary immune thrombocytopenia (ITP) in children is an acquired, immunologic, hemorrhagic disorder of childhood characterized by an isolated decrease in platelet count without a clear trigger. The main pathogenesis is an immune intolerance that mediates platelet immunodestruction and underproduction. The first-line treatment options for ITP are glucocorticoids and immunoglobulins, and TPO-RAs are the first choice for second-line treatment, including eltrombopag, hetrombopag, and avatrombopag and romiplostim. The 2019 International Consensus Report on the Investigation and Management of Primary Immune thrombocytopenia recommends that switching from one TPO-RA to another TPO-RA and sequential therapy in adult patients with multiple treatment failure have been shown to have positive effects on response and adverse events. However, in the treatment of childhood ITP, the experience of the conversion between TPO-RAs is insufficient. In this study, we retrospectively analyzed the treatment status of conversion of hetrombopag or eltrombopag to avatrombopag in children with ITP in our center, and explored the efficacy and safety of conversion therapy of avatrombopag.

Methods: A total of 11 patients with primary ITP who switched from hetrombopag or eltrombopag to avatrombopag for any reason between May 2021 and May 2023 were included in this study. Patients were ≤15 years of age, had been treated with hetrombopag or eltrombopag for at least 4 weeks, and the interval between discontinuation of hetrombopag or eltrombopag and initiation of avatrombopag was no more than 1 month. The secondary endpoint of observation was 2 weeks after switching to avatrombopa, and the primary endpoint was 3 months after switching to avatrombopa. Observations included platelet reactions, dose of avatrombopag, tapering of other immunosuppressive agents, and treatment-related adverse events.

Results: The median platelet count of patients was 30.1×10 ⁹/L (8.4×10 ⁹/L,89×10 ⁹/L) before treatment with avatrombopag, 253×10 ⁹/L (25×10 ⁹/L,1179×10 ⁹/L) after 2 weeks of avatrombopag（ P=0.003）, and after 3 months of avatrombopag the median platelet count was 343×10 ⁹/L (53×10 ⁹/L,803×10 ⁹/L) （ P=0.008）. The platelet response rate was 90.9% after 2 weeks of treatment with avatrombopag, with a complete response rate of 63.6%, a partial response rate of 27.3%, and a no response rate of 9.1%; the platelet response rate was 100% after 3 months of treatment with avatrombopag, with a complete response rate of 88.9% and a partial response rate of 11.1%. The median onset of action was 9 (3,21) days. During the observation period, 8 of 11 patients were able to achieve avatrombopag dose reduction therapy with a median time to dose reduction of 13 days (4,86).

Eight patients who were receiving concurrent immunosuppressive therapy prior to switching to avatrombopag, including six on prednisone and two on cyclosporine, were able to discontinue immunosuppressive therapy after switching to avatrombopag, with a median time to discontinuation of 18 days (12,24). The monitoring of liver and kidney functions, etc. during the observation period did not show any significant abnormality, and no thrombotic manifestations were found.

Conclusion: The results of the pediatric data analysis in this study validate the potential value of switching between TPO-RAs: when one TPO-RA fails to provide sufficient efficacy, switching to another TPO-RA treatment may have a positive effect.