Eltrombopag plus rhtpo versus eltrombopag for itp during the covid-19 pandemic (elaborate-19)
Authors: Z. Y. An, Y. He, X. L. Zhu, H. X. Fu, T. T. Han, X. Y. Zhao, X. L. Dou, Y. J. Chang, X. H. Zhang
Journal: HemaSphere (2021)

Background: Immune thrombocytopenia (ITP) is an acquired thrombocytopenia caused by immune-mediated platelet destruction and impaired platelet production. Recombinant human thrombopoietin (rhTPO) and Eltrombopag, a small molecule agonist of thrombopoietin receptor (TPO-RA), are both recommended as the subsequent treatment for ITP patients, which also already showed robust efficacy. They increase the number of platelets through different mechanisms, and previous studies demonstrated that they might exert synergic effect. During the COVID- 19 pandemic, the classical subsequent treatment regimen for ITP of immunosuppressants and/or steroids might increase patients' susceptibility of virus infections. The investigators hypothesized that the combination of these two agents could be a promising option for ITP treatment during the COVID-19 pandemic. To minimize ITP patients' risk during the COVID-19 global crisis and to improve treatment efficacy, this treatment regimen of Eltrombopag plus rhTPO should be investigated. This trial is registered with ClinicalTrials.gov, number NCT01667263. Aims: This study aimed to evaluate the sustained responses at 6 months and safety of Eltrombopag plus rhTPO as treatment for corticosteroid- resistant or relapsed ITP patients during the COVID-19 pandemic. Methods: In this open-label, randomized, phase 2 trial, we enrolled confirmed corticosteroid-resistant or relapsed adult ITP patients from 5 different tertiary medical centers in China. They were randomly assigned 1:1 with an interactive web-based response system to receive either Eltrombopag 25-75 mg oral daily according to platelet response plus rh-TPO 300U/kg subcutaneous injection once daily for 7 consecutive days, followed by a tapering dose in maintenance therapy or Eltrombopag monotherapy for 12 weeks (Figure 1). The primary endpoint was 6-month sustained response (SR) defined as platelet counts maintained > 30×109/L and at least a doubling of baseline platelet count. Key secondary endpoints were initial response by day 14, duration of response (DOR), TTR, bleeding scores, and adverse events (AEs). Results: Between August 2020, and March 2021, 60 patients were randomly allocated into either rh-TPO plus Eltrombopag (n=30) or Eltrombopag monotherapy (n=30). At the 6-month follow-up, the proportion of patients with SR was significantly higher in the rh-TPO plus Eltrombopag group than in the Eltrombopag monotherapy group (66.7% vs 36.7%, p= 0.020). The combination of rh-TPO and Eltrombopag resulted in a higher incidence of initial response by day 14 compared with Eltrombopag monotherapy (76.7% vs 60%, p= 0.165). Throughout the follow-up period, overall DOR was greater in the combination group, estimated by the Kaplan-Meier analysis. Bleeding was more effectively controlled in the rh-TPO plus Eltrombopag arm, with fewer bleeding events and lower bleeding scores. There was no difference between the 2 groups in terms of rescue treatments. All subjects tolerated the treatment well, and no grade 4 adverse events or treatment- related death were reported. No statistically significant differences were observed in the incidence of treatment-related AEs between the two groups. Summary/Conclusion: Rh-TPO plus Eltrombopag is an effective and safe treatment for corticosteroid-resistant or relapsed ITP patients during the COVID-19 pandemic. (NCT04516837).