Latest news on Eltrombopag/Eltrombopag

During the COVID-19 epidemic, the classic subsequent treatment regimen of immune thrombocytopenia (ITP) with immunosuppressives and/or steroids may increase patients' susceptibility to viral infection. To minimize the risk and improve treatment efficacy for ITP patients during the COVID-19 global crisis, non-immunosuppressive therapies (mainly including thrombopoietin mimetics such as eltrombopag or recombinant human thrombopoietin (rhTPO)) may be better for patients.

Eltrombopag, a small molecule agonist of thrombopoietin receptor (TPO-RA), is recommended for the subsequent treatment of ITP patients, and this treatment has also shown strong efficacy. However, serious problems with eltrombopag in the treatment of corticosteroid-resistant or recurrent ITP are ineffectiveness, loss of response, and platelet count fluctuations during treatment. RhTPO is a full-length glycosylated TPO produced from Chinese hamster ovary cells and has shown effectiveness in multiple studies on ITP. Due to the difference between rh-TPO and eltrombopag, it has different molecular structure, therapeutic mechanism and pharmacokinetic characteristics, and therefore has different response patterns and side effects. Previous studies have demonstrated the safety and efficacy of switching between rh-TPO and eltrombopag in patients with ITP who failed to respond or experienced adverse events with first-time TPO-RA. The researchers hypothesized that a combination of these two drugs might be a promising option for treating ITP.

The inclusion criteria are as follows: clinically proven corticosteroid resistance or relapsed primary ITP; platelet count less than 30×10^9/L twice or platelet count greater than 30×10^9/L combined with bleeding manifestations (World Health Organization Bleeding Scale level 2 or above); ≥18 years. For patients treated with the combination of eltrombopag and rhTPO, they received eltrombopag 25-75 mg orally and rhTPO 300 U/kg subcutaneously once a day for 7 days, and then gradually reduced the dose during maintenance treatment to maintain platelet counts between 50-150×10^9/L.

From September 2020 to July 2023, a total of 29 patients with corticosteroid-resistant or recurrent ITP were enrolled to receive eltrombopag plusrhTPO, including 11 male and 18 female patients. The median age is 55 years. Baseline platelet count is 7 (1-17) × 10^9/L. Most patients (69.0%) had severe ITP (platelet count ≤10×109/L or bleeding score ≥5). Efficacy was defined as a platelet count ≥30×10^9/L and ≥2 times the baseline platelet count after at least one treatment. The response rates at 1 week (early response) and 1 month (initial response) were 37.9% and 62.1%, respectively. After 6 weeks of treatment, 82.8% of patients achieved relief, and most patients (89.7%) had their bleeding symptoms improved. No thromboembolic events occurred during treatment.

Eltrombopag andrhTPO are safe and effective treatments for corticosteroid-resistant or recurrent ITP, especially severe ITP.