Relative potency of the thrombopoietin receptor agonists eltrombopag, avatrombopag and romiplostim in a patient with chronic immune thrombocytopenia

A 64-year-old woman with chronic autoimmune thrombocytopenia (ITP) secondary to systemic lupus erythematosus presented with platelet counts persistently ≤20 × 109/l with lower-extremity petechiae and frequent spontaneous ecchymoses. She had previously been treated with glucocorticoids, intravenous immunoglobulin, rituximab, anti-Rh D immune globulin and azathioprine, each without a durable response. She was initiated on a clinical trial of avatrombopag (E5501, previously known as AKR-501 and YM477), which, following dose titration to 30 mg daily, increased the platelet count to ≥100 × 109/l and caused mucocutaneous bleeding to stop. After 6 months of treatment with avatrombopag, the clinical trial ended and the patient was transitioned to eltrombopag. On a dose of eltrombopag 50–75 mg daily the platelet count stabilized in the 20–50 × 109/l range, and the patient's bleeding symptoms returned when the platelet count was ≤30 × 109/l. Because of this, she was transitioned to romiplostim, resulting in a platelet count in the 200–300 × 109/l range. The patient received no rescue treatment over this clinical course. The graph demonstrates the patient's platelet count response to three different thrombopoietin receptor agonists, with the magnitude of the response being comparable to that seen at usual ITP doses with each drug when administered to healthy volunteers. At maximal doses tested in healthy volunteers, daily 20 mg doses of avatrombopag (red) produced a peak platelet count 3–5 times higher than with daily 75 mg doses of eltrombopag (green), and romiplostim (blue) at maximal doses produced a peak platelet count 8–10 times higher than with maximal doses of eltrombopag. Dosing for each agent is shown above the platelet trend line, and median platelet counts demonstrating the treatment effect for each agent are given in an inset bar graph.