Avatrombopag for the Treatment of Adult Patients with Chronic Immune Thrombocytopenia (cITP): Focus on Patient Selection and Perspectives

Overview

Journal Ther Clin Risk Manag

Publisher Dove Medical Press

Date 2022 Apr 7

PMID 35386180

Authors

Galina Tsykunova

Waleed Ghanima

Affiliations

Soon will be listed here.

Abstract

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a reduced number of circulating platelets due to immune-mediated destruction and decreased platelet production in the bone marrow. Thrombopoietin receptor agonists (TPO-RAs) are highly effective and widely used in the treatment of patients with steroid treatment failure or dependency. Avatrombopag represents a new supplement to the TPO-RAs family. It was originally approved for the treatment of thrombocytopenia in patients with chronic liver disease who are scheduled to undergo an invasive procedure. However, labeled indications for avatrombopag have been relatively recently expanded to include treatment of chronic ITP in adults with insufficient response to the previous treatments. In this article, we provide an overview of pharmacodynamics and pharmacokinetics of avatrombopag as well as results of the clinical trials related to safety and efficacy of avatrombopag with a perspective on current clinical use. Available data so far suggests that avatrombopag can be effectively used in ITP patients and has a favorable safety profile. Though further studies are needed to affirm the efficacy and safety, avatrombopag has the potential to become a TPO agonist of choice for many patients with ITP.

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References

Ghanima W, Gernsheimer T, Kuter D . How I treat primary ITP in adult patients who are unresponsive to or dependent on corticosteroid treatment. Blood. 2021; 137(20):2736-2744. DOI: 10.1182/blood.2021010968. View

Cooper N, Ghanima W . Immune Thrombocytopenia. N Engl J Med. 2019; 381(10):945-955. DOI: 10.1056/NEJMcp1810479. View

Cooper N, Kruse A, Kruse C, Watson S, Morgan M, Provan D . Immune thrombocytopenia (ITP) World Impact Survey (iWISh): Patient and physician perceptions of diagnosis, signs and symptoms, and treatment. Am J Hematol. 2020; 96(2):188-198. PMC: 7898610. DOI: 10.1002/ajh.26045. View

Frederiksen H, Schmidt K . The incidence of idiopathic thrombocytopenic purpura in adults increases with age. Blood. 1999; 94(3):909-13. View

Gonzalez-Lopez T, Pascual C, Alvarez-Roman M, Fernandez-Fuertes F, Sanchez-Gonzalez B, Caparros I . Successful discontinuation of eltrombopag after complete remission in patients with primary immune thrombocytopenia. Am J Hematol. 2014; 90(3):E40-3. DOI: 10.1002/ajh.23900. View

Fukushima-Shintani M, Suzuki K, Iwatsuki Y, Abe M, Sugasawa K, Hirayama F . AKR-501 (YM477) a novel orally-active thrombopoietin receptor agonist. Eur J Haematol. 2009; 82(4):247-54. DOI: 10.1111/j.1600-0609.2008.01198.x. View

Wang L, Gao Z, Chen X, Zhang H, Yang N, Wang F . Efficacy and safety of thrombopoietin receptor agonists in patients with primary immune thrombocytopenia: A systematic review and meta-analysis. Sci Rep. 2016; 6:39003. PMC: 5171907. DOI: 10.1038/srep39003. View

cervinek L, Mayer J, Doubek M . Sustained remission of chronic immune thrombocytopenia after discontinuation of treatment with thrombopoietin-receptor agonists in adults. Int J Hematol. 2015; 102(1):7-11. DOI: 10.1007/s12185-015-1793-1. View

Mahevas M, Fain O, Ebbo M, Roudot-Thoraval F, Limal N, Khellaf M . The temporary use of thrombopoietin-receptor agonists may induce a prolonged remission in adult chronic immune thrombocytopenia. Results of a French observational study. Br J Haematol. 2014; 165(6):865-9. DOI: 10.1111/bjh.12888. View

10.

Al-Samkari H . Avatrombopag maleate for the treatment of periprocedural thrombocytopenia in patients with chronic liver disease. Drugs Today (Barc). 2018; 54(11):647-655. DOI: 10.1358/dot.2018.54.11.2899441. View

11.

Terrault N, Hassanein T, Howell C, Joshi S, Lake J, Sher L . Phase II study of avatrombopag in thrombocytopenic patients with cirrhosis undergoing an elective procedure. J Hepatol. 2014; 61(6):1253-9. DOI: 10.1016/j.jhep.2014.07.007. View

12.

Gonzalez-Porras J, Godeau B, Carpenedo M . Switching thrombopoietin receptor agonist treatments in patients with primary immune thrombocytopenia. Ther Adv Hematol. 2019; 10:2040620719837906. PMC: 6515841. DOI: 10.1177/2040620719837906. View

13.

Li J, Yang C, Xia Y, Bertino A, Glaspy J, Roberts M . Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood. 2001; 98(12):3241-8. DOI: 10.1182/blood.v98.12.3241. View

14.

Neunert C, Terrell D, Arnold D, Buchanan G, Cines D, Cooper N . American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019; 3(23):3829-3866. PMC: 6963252. DOI: 10.1182/bloodadvances.2019000966. View

15.

Michelson A, Smolensky Koganov E, Forde E, Carmichael S, Frelinger 3rd A . Avatrombopag increases platelet count but not platelet activation in patients with thrombocytopenia resulting from liver disease. J Thromb Haemost. 2018; 16(12):2515-2519. DOI: 10.1111/jth.14295. View

16.

Fukushima-Shintani M, Suzuki K, Iwatsuki Y, Abe M, Sugasawa K, Hirayama F . AKR-501 (YM477) in combination with thrombopoietin enhances human megakaryocytopoiesis. Exp Hematol. 2008; 36(10):1337-42. DOI: 10.1016/j.exphem.2008.04.020. View

17.

Makar R, Zhukov O, Sahud M, Kuter D . Thrombopoietin levels in patients with disorders of platelet production: diagnostic potential and utility in predicting response to TPO receptor agonists. Am J Hematol. 2013; 88(12):1041-4. DOI: 10.1002/ajh.23562. View

18.

Kuter D . The structure, function, and clinical use of the thrombopoietin receptor agonist avatrombopag. Blood Rev. 2021; 53:100909. DOI: 10.1016/j.blre.2021.100909. View

19.

Kaushansky K . The molecular mechanisms that control thrombopoiesis. J Clin Invest. 2005; 115(12):3339-47. PMC: 1297257. DOI: 10.1172/JCI26674. View

20.

Cooper N, Kruse A, Kruse C, Watson S, Morgan M, Provan D . Immune thrombocytopenia (ITP) World Impact Survey (I-WISh): Impact of ITP on health-related quality of life. Am J Hematol. 2020; 96(2):199-207. PMC: 7898815. DOI: 10.1002/ajh.26036. View