Eltrombopag in Immune Thrombocytopenia, Aplastic Anemia, and Myelodysplastic Syndrome: From Megakaryopoiesis to Immunomodulation
Autor: | Wilma Barcellini, Ramona Cassin, Giorgia Levati, Bruno Fattizzo |
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Rok vydání: | 2019 |
Předmět: |
medicine.medical_treatment
Eltrombopag Context (language use) Benzoates Immunomodulation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine hemic and lymphatic diseases medicine Humans Pharmacology (medical) Aplastic anemia Megakaryopoiesis Immunosuppression Therapy Thrombopoietin receptor Purpura Thrombocytopenic Idiopathic business.industry Myelodysplastic syndromes Anemia Aplastic Immunosuppression medicine.disease Hydrazines medicine.anatomical_structure chemistry Myelodysplastic Syndromes 030220 oncology & carcinogenesis Immunology Pyrazoles Bone marrow business Megakaryocytes Receptors Thrombopoietin 030217 neurology & neurosurgery |
Zdroj: | Drugs. 79:1305-1319 |
ISSN: | 1179-1950 0012-6667 |
Popis: | Eltrombopag is an orally available thrombopoietin receptor agonist indicated for the treatment of immune thrombocytopenia (ITP). Beyond the effect on megakaryopoiesis, the drug also showed a stimulating effect on the hematopoietic stem cell with consistent clinical efficacy in aplastic anemia (AA) and myelodysplastic syndromes (MDS). Eltrombopag is highly effective in ITP and less so in AA and MDS. This observation underlines the importance of residual normal hematopoiesis, which is maximal in ITP, minimal/absent in AA, and dysregulated in MDS. In ITP, the drug at 50-75 mg daily induced up to 85% responses both in clinical trials and real-life studies, with the possibility of tapering and discontinuation. In AA, eltrombopag at 150 mg daily was effective in about 40% of cases relapsed/refractory to standard immunosuppression or ineligible for bone marrow transplant. In MDS, the drug seems less effective, with responses in about a quarter of patients at various schedules. The efficacy of eltrombopag in ITP, AA, and MDS suggests the existence of common immune-pathological mechanisms in these diseases, including autoimmunity against peripheral blood cells and bone marrow precursors, as well as a possible evolution of one condition into the other. Additional mechanisms of action emerging from the clinical use of eltrombopag include modulation of T-regulatory cells, restoration of Fc-γ receptor balance in phagocytes, and an iron-mobilizing effect. In this review, we analyzed the most recent literature on eltrombopag use and efficacy in patients with ITP, AA, and MDS, exploring the basis for different dosing, combined treatments, and discontinuation in each context. |
Databáze: | OpenAIRE |
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