Eltrombopag, a thrombopoietin- receptor agonist in the treatment of adult chronic immune thrombocytopenia: A review of the efficacy and safety profile

Therapeutic Advances in Hematology

Volumn 3, Issue 3, 2012, Pages 155-164

  Cheng, Gregory ^a  

^a Dr Stanley Ho Medical Development Foundation   (Hong Kong)

Author keywords

eltrombopag; immune thrombocytopenia; thrombopoietin receptor agonist

Indexed keywords

AZATHIOPRINE; CORTICOSTEROID; CYCLOSPORIN A; DANAZOL; ELTROMBOPAG; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PLACEBO;

AUTOIMMUNE THROMBOCYTOPENIA; CHRONIC IMMUNE THROMBOCYTOPENIA; DOSE CALCULATION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG HALF LIFE; DRUG MECHANISM; DRUG SAFETY; DRUG WITHDRAWAL; HUMAN; MULTIPLE CYCLE TREATMENT; NEPHROTOXICITY; NONHUMAN; PATIENT COMPLIANCE; PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW; THROMBOEMBOLISM;

EID: 84993709956     PISSN: 20406207     EISSN: 20406215     Source Type: Journal    
DOI: 10.1177/2040620712442525     Document Type: Article

References (46)

1. Bae S.H. Ryoo H.M. Lee W.S. Joo Y.D. Lee K.H. Lee J.H. et al. (2011) High dose dexamrthasone vs conventional dose prednisolone for adults with immune thrombocytopenia: a prospective multicenter phase III trial. Blood 116: 1512.
2. Basser R.L. O'Flaherty E. Green M. Edmonds M. Nichol J. Menchaca D.M. et al. (2002) Development of pancytopenia with neutralizing antibodies to thrombopoietin after multicycle chemotherapy supported by megakaryocyte growth and development factor. Blood 99: 2599–2602.
3. Ben-Yehuda D. Gillis S. Eldor A. (1994) Clinical and therapeutic experience in 712 Israeli patients with idiopathic thrombocytopenic purpura. Israeli ITP Study Group. Acta Haematol 91: 1–6.
4. Boruchov D.M. Gururangan S. Driscoll M.C. Bussel J.B. (2007) Multiagent induction and maintenance therapy for patients with refractory immune thrombocytopenic purpura (ITP). Blood 110: 3526–3531.
5. Bussel J.B. Cheng G. Saleh M.N. Psaila B. Kovaleva L. Meddeb B. et al. (2007) Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 357: 2237–2247.
6. Bussel J.B. Provan D. Shamsi T. Cheng G. Psaila B. Kovaleva L. et al. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. The Lancet 373: 641–648.
7. Bussel J. Psaila B. Saleh M. Vasey S. Mayer B. Stone N. et al. (2008) Efficacy and safety of repeated intermittent treatment with eltrombopag in patients with chronic idiopathic thrombocytopenic purpura. Blood 112: 1176.
8. Carson K.R. Evens A.M. Richey E.A. Habermann T.M. Focosi D. Seymour J.F. et al. (2009) Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood 113: 4834–4840.
9. Chang M. Nakagawa P.A. Williams S.A. Schwartz M.R. Imfeld K.L. Buzby J.S. et al. (2003) Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro. Blood 102: 887–895.
10. Cheng G. Federiksen H. Bakshi K. Bailey C. Brainsky A. (2011 a) Prolonged response to eltrombopag in patients with chronic ITP. Haematologica 96 (Suppl. 2): 331.
11. Cheng G. Saleh M. Marcher C. Vasey S. Mayer B. Aivado M. et al. (2011 b) Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomized phase 3 study. The Lancet 377: 393–402.
12. Cheng Y. Wong R.S. Soo Y.O. Chui C.H. Lau F.Y. Chan N. et al. (2003) Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med 349: 831–836.
13. Cines D.B. Blanchette V.S. (2002) Immune thrombocytopenic purpura. N Engl J Med 346: 995–1008.
14. Cohen Y.C. Djulbegovic B. Shamai-Lubovitz O. Mozes B. (2000) The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch Intern Med 160: 1630–1638.
15. Douglas V. Tallman M. Cripe L. Peterson L.C. (2002) Thrombopoietin administered during induction chemotherapy to patients with acute myeloid leukemia induces transient morphologic changes that may resemble chronic myeloproliferative disorders. Am J Clin Pathol 117: 844–850.
16. Erhardt J. Erickson-Miller C.L. Tapley P. (2004) SB 497115-GR, a low molecular weight TPOR agonist, does not induce platelet activation or enhance agonist-induced platelet aggregation in vitro. Blood 104: 59b.
17. Erickson-Miller C.L. de Lorme E. Tian S.S. Hopson C.B. Stark K. Giampa L. et al. (2005) Discovery and characterization of a selective, nonpeptidyl thrombopoietin receptor agonist. Exp Hematol 33: 85–93.
18. European Medicine Agency (2009) Revolade (eltrombopag). London: European Medicines agency. Available at http://www.ema.europa.eu (accessed 1 March 2012).
19. Fianchi L. Rossi E. Murri R. de Stefano V. Pagano L. Leone G. (2007) Severe infectious complications in a patient treated with rituximab for idiopathic thrombocytopenic purpura. Ann Hematol 86: 225–226.
20. George J.N. Raskob G.E. Vesely S.K. Moore D. Jr Lyons R.M. Cobos E. et al. (2003) Initial management of immune thrombocytopenic purpura in adults: a randomized controlled trial comparing intermittent anti-D with routine care. Am J Hematol 74: 161–169.
21. Glaxo Smith Kline (2011) Promacta (eltrombopag tablets): US prescribing information. Available at http://us.gsk.com/products/assets/us_promacta.pdf (accessed 31 October 2011).
22. Godeau B. Porcher R. Fain O. Lefrère F. Fenaux P. Cheze S. et al. (2008) Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study. Blood 112: 999–1004.
23. Hernández F. Linares M. Colomina P. Pastor E. Cerveró A. Pérez A. et al. (1995) Dapsone for refractory chronic idiopathic thrombocytopenic purpura. Br J Haematol 90: 473–475.
24. Hoffman R. Zaknoen S. Yang H.H. Bruno E. Lo Buglio A.F. Arrowsmith J.B. et al. (1985) An antibody cytotoxic to megakaryocyte progenitor cells in a patient with immune thrombocytopenic purpura. N Engl J Med 312: 1170–1174.
25. Houwerzijl E.J. Blom N.R. van der Want J.J. Louwes H. Esselink M.T. Smit J.W. et al. (2004) Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura. Blood 103: 500–506.
26. Kappers-Klunne M.C. van't Veer M.B. (2001) Cyclosporin A for the treatment of patients with chronic idiopathic thrombocytopenic purpura refractory to corticosteroids or splenectomy. Br J Haematol 114: 121–125.
27. Kojouri K. Vesely S.K. Terrell D.R. George J.N. (2004) Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood 104: 2623–2634.
28. Kotb R. Pinganaud C. Trichet C. Lambotte O. Dreyfus M. Delfraissy J.F. et al. (2005) Efficacy of mycophenolate mofetil in adult refractory auto-immune cytopenias: a single center preliminary study. Eur J Haematol 75: 60–64.
29. Li J. Yang C. Xia Y. Bertino A. Glaspy J. Roberts M. et al. (2001) Thrombocytopenia caused by the development of antibodies to thrombopoietin. Blood 98: 3241–3248.
30. Maloisel F. Andres E. Zimmer J. Noel E. Zamfir A. Koumarianou A. et al. (2004) Danazol therapy in patients with chronic idiopathic thrombocytopenic purpura: long-term results. Am J Med 116: 590–594.
31. Mazzucconi M.G. Fazi P. Bernasconi S. de Rossi G. Leone G. Gugliotta L. et al. (2007) Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood 109: 1401–1407.
32. McMillan R. Wang L. Tomer A. Nichol J. Pistillo J. (2004) Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood 103: 1364–1369.
33. Nomura S. Dan K. Hotta T. Fujimura K. Ikeda Y. (2002) Effects of pegylated recombinant human megakaryocyte growth and development factor in patients with idiopathic thrombocytopenic purpura. Blood 100: 728–730.
34. Pizzuto J. Ambriz R. (1984) Therapeutic experience on 934 adults with idiopathic thrombocytopenic purpura: multicentric trial of the Cooperative Latin American Group on Hemostasis and Thrombosis. Blood 64: 1179–1183.
35. Portielje J.E. Westendorp R.G. Kluin-Nelemans H.C. Brand A. (2001) Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood 97: 2549–2554.
36. Provan D. Stasi R. Newland A.C. Blanchette V. Bolton-Maggs P. Bussel J. et al. (2010) International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 115: 168–186.
37. Reiner A. Gernsheimer T. Slichter S.J. (1995) Pulse cyclophosphamide therapy for refractory autoimmune thrombocytopenic purpura. Blood 85: 351–358.
38. Rodeghiero F. Stasi R. Gernsheimer T. Michel M. Provan D. Arnold D.M. et al. (2008) Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura (ITP) of adults and children: report from an international working group. Blood 113: 2386–2393.
39. Saleh M. Cheng G. Bussel J. Burgess P. Marcello L. Bailey C. et al. (2011) EXTEND study update: safety and efficacy of eltrombopag in adults with chronic immune thrombocytopenia (ITP) from June 2006 to February 2011. Blood 118: 24.
40. Sarpatwari A. Bennett D. Logie J.W. Shukla A. Beach K.J. Newland A.C. et al. (2010) Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database. Haematologica 95: 1167–1175.
41. Scaradavou A. Woo B. Woloski B.M. Cunningham-Rundles S. Ettinger L.J. Aledort L.M. et al. (1997) Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients. Blood 89: 2689–2700.
42. Schwartz J. Leber M.D. Gillis S. Giunta A. Eldor A. Bussel J.B. (2003) Long term follow-up after splenectomy performed for immune thrombocytopenic purpura (ITP). Am J Hematol 72: 94–98.
43. Spahr J.E. Rodgers G.M. (2008) Treatment of immune-mediated thrombocytopenia purpura with concurrent intravenous immunoglobulin and platelet transfusion: a retrospective review of 40 patients. Am J Hematol 83: 122–125.
44. Wang B. Nichol J.L. Sullivan J.T. (2004) Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther 76: 628–638.
45. Zaja F. Baccarani M. Mazza P. Bocchia M. Gugliotta L. Zaccaria A. et al. (2010) Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia. Blood 115: 2755–2762.
46. Zhao Y.Q. Wang Q.Y. Zhai M. Xu J. Chen X.Q. Liu W.L. et al. (2004) A multi-center clinical trial of recombinant human thrombopoietin in chronic refractory idiopathic thrombocytopenic purpura. Zhonghua Nei Ke Za Zhi 43: 608–610.