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Cardiovascular & Hematological Agents in Medicinal Chemistry

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ISSN (Print): 1871-5257
ISSN (Online): 1875-6182

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Meta-Analysis

Safety and Efficacy of Eltrombopag in Children and Adults with Immune Thrombocytopenia: A Systematic Review and Meta-Analysis

Author(s): Savvas Kolanis, Eleni Vasileiou, Emmanuel Hatzipantelis, Marina Economou and Athanasios Tragiannidis*

Volume 19, Issue 1, 2021

Published on: 10 September, 2020

Page: [83 - 92] Pages: 10

DOI: 10.2174/1871525718666200910161540

Price: $65

Abstract

Immune thrombocytopenia is an immune condition where antibodies are produced against platelets. Eltrombopag is a thrombopoietin receptor agonist that stimulates and promotes platelet production approved for treating thrombocytopenia in patients with chronic immune thrombocytopenia, where other treatments such as corticosteroids, splenectomy or immunoglobulins are inadequate. The aim of this meta-analysis was to evaluate the efficacy and safety of the eltrombopag in adults and children with immune thrombocytopenia. We included 7 studies with a total of 765 patients (606 adults and 159 children). We evaluated the number of patients that achieved a post-treatment platelet count equal or above 50x109/L (primary result-target) without the need of rescue treatment for at least 4 weeks. Our data showed that patients who received eltrombopag were almost 4 times more probable in achieving the primary target when compared to patients who received placebo (RR 3.84, 95% CI 2.39 to 6.14; I2 = 46%). The number of patients needed rescue treatment and the number of bleeding incidents were reduced in the group that received eltrombopag when compared to those who received placebo (RR 0.40, 95% CI 0.25 to 0.62; I2 = 40%) (RR 0.74, 95% CI 0.62 to 0.89; I2 = 68%). The total number of side effects did not statistically differ between the two groups (RR 0.99, 95% CI 0.90 to 1.08; I2 = 14%). Our findings were similar to previously published studies and confirm that eltrombopag is safe and efficient in immune thrombocytopenia. However, more clinical trials are needed in order to enhance our findings.

Keywords: Immune thrombocytopenia, eltrombopag, thrombocytopenia, aplastic anemia, antibodies, megakaryocytes.

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[1]
Buchanan, G.R. Immune thrombocytopenia during childhood: New approaches to classification and management. J. Pediatr., 2014, 165(3), 437-439.
[http://dx.doi.org/10.1016/j.jpeds.2014.05.030] [PMID: 24973290]
[2]
Merli, P.; Strocchio, L.; Vinti, L.; Palumbo, G.; Locatelli, F. Eltrombopag for treatment of thrombocytopenia-associated disorders. Expert Opin. Pharmacother., 2015, 16(14), 2243-2256.
[http://dx.doi.org/10.1517/14656566.2015.1085512] [PMID: 26364898]
[3]
Mahévas, M.; Fain, O.; Ebbo, M.; Roudot-Thoraval, F.; Limal, N.; Khellaf, M.; Schleinitz, N.; Bierling, P.; Languille, L.; Godeau, B.; Michel, 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), 865-869.
[http://dx.doi.org/10.1111/bjh.12888] [PMID: 24725224]
[4]
Kolonić, S.O.; Patekar, M.B.; Milunović, V. [Diagnostic approach and treatment of immune thrombocytopenia in adults]. Acta Med. Croatica, 2013, 67(1), 3-11.http://www.ncbi.nlm.nih.gov/pubmed/24279250
[PMID: 24279250]
[5]
Garnock-Jones, K.P. Eltrombopag: A review of its use in treatment-refractory chronic primary immune thrombocytopenia. Drugs, 2011, 71(10), 1333-1353.
[http://dx.doi.org/10.2165/11207390-000000000-00000] [PMID: 21770480]
[6]
Zeller, B.; Helgestad, J.; Hellebostad, M. Immune thrombocytopenic purpura in childhood in Norway: A prospective, population based registration. Pediatr Hematol Oncol. , 17(7), 551-558. [Online: http://www.ncbi.nlm.nih.gov/pubmed/11033730] [Accessed: February 17, 2019].
[http://dx.doi.org/10.1080/08880010050122816]
[7]
Ramaswamy, K.; Hsieh, L.; Leven, E.; Thompson, M.V.; Nugent, D.; Bussel, J.B. Thrombopoietic agents for the treatment of persistent and chronic immune thrombocytopenia in children. J. Pediatr., 2014, 165(3), 600-5.e4.
[http://dx.doi.org/10.1016/j.jpeds.2014.03.060] [PMID: 24857517]
[8]
Reid, M.M. Chronic idiopathic thrombocytopenic purpura: Incidence, treatment, and outcome. Arch. Dis. Child., 1995, 72(2), 125-128.
[http://dx.doi.org/10.1136/adc.72.2.125] [PMID: 7702373]
[9]
Grainger, J.D.; Locatelli, F.; Chotsampancharoen, T.; Donyush, E.; Pongtanakul, B.; Komvilaisak, P.; Sosothikul, D.; Drelichman, G.; Sirachainan, N.; Holzhauer, S.; Lebedev, V.; Lemons, R.; Pospisilova, D.; Ramenghi, U.; Bussel, J.B.; Bakshi, K.K.; Iyengar, M.; Chan, G.W.; Chagin, K.D.; Theodore, D.; Marcello, L.M.; Bailey, C.K. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): A randomised, multicentre, placebo-controlled trial. Lancet, 2015, 386(10004), 1649-1658.
[http://dx.doi.org/10.1016/S0140-6736(15)61107-2] [PMID: 26231455]
[10]
Bussel, J.B.; de Miguel, P.G.; Despotovic, J.M.; Grainger, J.D.; Sevilla, J.; Blanchette, V.S.; Krishnamurti, L.; Connor, P.; David, M.; Boayue, K.B.; Matthews, D.C.; Lambert, M.P.; Marcello, L.M.; Iyengar, M.; Chan, G.W.; Chagin, K.D.; Theodore, D.; Bailey, C.K.; Bakshi, K.K. Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): A randomised, multicentre, placebo-controlled study. Lancet Haematol., 2015, 2(8), e315-e325.
[http://dx.doi.org/10.1016/S2352-3026(15)00114-3] [PMID: 26688484]
[11]
Tomiyama, Y.; Miyakawa, Y.; Okamoto, S.; Katsutani, S.; Kimura, A.; Okoshi, Y.; Ninomiya, H.; Kosugi, H.; Nomura, S.; Ozaki, K.; Ikeda, Y.; Hattori, T.; Katsura, K.; Kanakura, Y. A lower starting dose of eltrombopag is efficacious in Japanese patients with previously treated chronic immune thrombocytopenia. J. Thromb. Haemost., 2012, 10(5), 799-806.
[http://dx.doi.org/10.1111/j.1538-7836.2012.04695.x] [PMID: 22409309]
[12]
Bussel, J.B.; Cheng, G.; Saleh, M.N.; Psaila, B.; Kovaleva, L.; Meddeb, B.; Kloczko, J.; Hassani, H.; Mayer, B.; Stone, N.L.; Arning, M.; Provan, D.; Jenkins, J.M. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N. Engl. J. Med., 2007, 357(22), 2237-2247.
[http://dx.doi.org/10.1056/NEJMoa073275] [PMID: 18046028]
[13]
Cheng, G.; Saleh, M.N.; Marcher, C.; Vasey, S.; Mayer, B.; Aivado, M.; Arning, M.; Stone, N.L.; Bussel, J.B. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet, 2011, 377(9763), 393-402.
[http://dx.doi.org/10.1016/S0140-6736(10)60959-2] [PMID: 20739054]
[14]
Kuter, D.J. The biology of thrombopoietin and thrombopoietin receptor agonists. Int. J. Hematol., 2013, 98(1), 10-23.
[http://dx.doi.org/10.1007/s12185-013-1382-0] [PMID: 23821332]
[15]
Kuter, D.J. Milestones in understanding platelet production: A historical overview. Br. J. Haematol., 2014, 165(2), 248-258.
[http://dx.doi.org/10.1111/bjh.12781] [PMID: 24528208]
[16]
Justiz Vaillant, A.A.; Gupta, N. Thrombocytopenic Purpura Immune., StatPearls Publishing; 2018. [Online: http://www.ncbi.nlm.nih.gov/pubmed/30725925], [Accessed February 18, 2019].
[17]
Hedman, A.; Henter, J.I.; Hedlund, I.; Elinder, G. Prevalence and treatment of chronic idiopathic thrombocytopenic purpura of childhood in Sweden. Acta Paediatr., 1997, 86(2), 226-227.http://www.ncbi.nlm.nih.gov/pubmed/9055900
[http://dx.doi.org/10.1111/j.1651-2227.1997.tb08876.x] [PMID: 9055900]
[18]
Fogarty, P.F.; Tarantino, M.D.; Brainsky, A.; Signorovitch, J.; Grotzinger, K.M. Selective validation of the WHO bleeding scale in patients with chronic immune thrombocytopenia. Curr. Med. Res. Opin., 2012, 28(1), 79-87.
[http://dx.doi.org/10.1185/03007995.2011.644849] [PMID: 22117897]
[19]
Neunert, C.; Lim, W.; Crowther, M.; Cohen, A.; Solberg, L., Jr; Crowther, M.A. American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood, 2011, 117(16), 4190-4207.
[http://dx.doi.org/10.1182/blood-2010-08-302984] [PMID: 21325604]
[20]
Bergmann, S. Proactive use of eltrombopag before the onset of clinical bleeding in two children with immune thrombocytopenia and lifestyle restrictions. Clin. Case Rep., 2017, 5(10), 1660-1663.
[http://dx.doi.org/10.1002/ccr3.1086] [PMID: 29026567]
[21]
Mantadakis, E.; Farmaki, E.; Buchanan, G.R. Thrombocytopenic purpura after measles-mumps-rubella vaccination: A systematic review of the literature and guidance for management. J. Pediatr., 2010, 156(4), 623-628.
[http://dx.doi.org/10.1016/j.jpeds.2009.10.015] [PMID: 20097358]
[22]
Boyers, D.; Jia, X.; Jenkinson, D. Lancet; Eltrombopag, Duan X., Ed.; , 2011, 373, pp. 1333-1353.
[23]
Zhang, J.; Liang, Y.; Ai, Y.; Li, X.; Xie, J.; Li, Y.; Zheng, W.; He, R. Eltrombopag versus romiplostim in treatment of children with persistent or chronic immune thrombocytopenia: A systematic review incorporating an indirect-comparison meta-analysis. Sci. Rep., 2018, 8(1), 576.
[http://dx.doi.org/10.1038/s41598-017-19099-8] [PMID: 29330464]
[24]
Dmytrijuk, A.; Robie-Suh, K.; Rieves, D.; Pazdur, R. Eltrombopag for the treatment of chronic immune (idiopathic) thrombocytopenic purpura. Oncology (Williston Park), 2009, 23(13), 1171-1177. [Online: http://www.ncbi.nlm.nih.gov/pubmed/20043468]
[PMID: 20043468]
[25]
Panzer, S.; Pabinger, I. Eltrombopag in chronic idiopathic thrombocytopenic purpura. Lancet, 2009, 373(9664), 607-608.
[http://dx.doi.org/10.1016/S0140-6736(09)60377-9] [PMID: 19231614]
[26]
Yang, R.; Li, J.; Jin, J.; Huang, M.; Yu, Z.; Xu, X.; Zhang, X.; Hou, M. Multicentre, randomised phase III study of the efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia. Br. J. Haematol., 2017, 176(1), 101-110.
[http://dx.doi.org/10.1111/bjh.14380] [PMID: 27734464]
[27]
Garnock-Jones, K.P.; Keam, S.J. Eltrombopag. Drugs, 2009, 69(5), 567-576.
[http://dx.doi.org/10.2165/00003495-200969050-00005] [PMID: 19368418]
[28]
Bussel, J.B.; Provan, D.; Shamsi, T.; Cheng, G.; Psaila, B.; Kovaleva, L.; Salama, A.; Jenkins, J.M.; Roychowdhury, D.; Mayer, B.; Stone, N.; Arning, M. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: A randomised, double-blind, placebo-controlled trial. Lancet, 2009, 373(9664), 641-648.
[http://dx.doi.org/10.1016/S0140-6736(09)60402-5] [PMID: 19231632]
[29]
Burness, C.B.; Keating, G.M.; Garnock-Jones, K.P. Eltrombopag: A review in paediatric chronic immune thrombocytopenia. Drugs, 2016, 76(8), 869-878.
[http://dx.doi.org/10.1007/s40265-016-0581-4] [PMID: 27151255]
[30]
Tripathi, A.K.; Shukla, A.; Mishra, S.; Yadav, Y.S.; Yadav, D.K. Eltrombopag therapy in newly diagnosed steroid non-responsive ITP patients. Int. J. Hematol., 2014, 99(4), 413-417.
[http://dx.doi.org/10.1007/s12185-014-1533-y] [PMID: 24526570]
[31]
Kühne, T.; Imbach, P. Eltrombopag: An update on the novel, non-peptide thrombopoietin receptor agonist for the treatment of immune thrombocytopenia. Ann. Hematol., 2010, 89(S1)(Suppl. 1), 67-74.
[http://dx.doi.org/10.1007/s00277-010-0953-x] [PMID: 20405290]
[32]
González, K.J.; Zuluaga, S.O.; DaRos, C.V.; Rodríguez, P.P.; Martí, A.C. Sequential treatment with thrombopoietin-receptor agonists (TPO-RAs) in immune thrombocytopenia (ITP): Experience in our center. Ann. Hematol., 2017, 96(3), 507-508.
[http://dx.doi.org/10.1007/s00277-016-2896-3] [PMID: 27975127]
[33]
Garzon, A.M.; Mitchell, W.B. Use of thrombopoietin receptor agonists in childhood immune thrombocytopenia. Front Pediatr., 2015, 3, 70.
[http://dx.doi.org/10.3389/fped.2015.00070] [PMID: 26322297]
[34]
Neunert, C.; Despotovic, J.; Haley, K.; Lambert, M.P.; Nottage, K.; Shimano, K.; Bennett, C.; Klaassen, R.; Stine, K.; Thompson, A.; Pastore, Y.; Brown, T.; Forbes, P.W.; Grace, R.F. Pediatric ITP Consortium of North America (ICON). Thrombopoietin receptor agonist use in children: Data from the pediatric ITP Consortium of North America ICON2 study. Pediatr. Blood Cancer, 2016, 63(8), 1407-1413.
[http://dx.doi.org/10.1002/pbc.26003] [PMID: 27135461]
[35]
Osman, M.E. Chronic immune thrombocytopenia in a child responding only to thrombopoietin receptor agonist. Sudan. J. Paediatr., 2012, 12(2), 60-64. [Online: http://www.ncbi.nlm.nih.gov/pubmed/27493347]
[PMID: 27493347]
[36]
Ehrlich, L.A.; Kwitkowski, V.E.; Reaman, G.; Ko, C.W.; Nie, L.; Pazdur, R.; Farrell, A.T. U.S. Food and drug administration approval summary: Eltrombopag for the treatment of pediatric patients with chronic immune (idiopathic) thrombocytopenia. Pediatr. Blood Cancer, 2017, 64(12), e26657.
[http://dx.doi.org/10.1002/pbc.26657] [PMID: 28627134]
[37]
Revolade 75 mg film-coated tablets - Summary of Product Characteristics (SmPC) - (eMC). [Online: https://www.medicines.org.uk/emc/product/508/smpc], [Accessed: February 23, 2019].
[38]
Miano, M.; Dufour, C. The diagnosis and treatment of aplastic anemia: a review. Int. J. Hematol., 2015, 101(6), 527-535.
[http://dx.doi.org/10.1007/s12185-015-1787-z] [PMID: 25837779]
[39]
Killick, S.B.; Bown, N.; Cavenagh, J.; Dokal, I.; Foukaneli, T.; Hill, A.; Hillmen, P.; Ireland, R.; Kulasekararaj, A.; Mufti, G.; Snowden, J.A.; Samarasinghe, S.; Wood, A.; Marsh, J.C. British Society for standards in haematology. Guidelines for the diagnosis and management of adult aplastic anaemia. Br. J. Haematol., 2016, 172(2), 187-207.
[http://dx.doi.org/10.1111/bjh.13853] [PMID: 26568159]
[40]
Boyers, D.; Jia, X.; Jenkinson, D.; Mowatt, G. Eltrombopag for the treatment of chronic immune or idiopathic thrombocytopenic purpura: A NICE single technology appraisal. Pharmacoeconomics, 2012, 30(6), 483-495.
[http://dx.doi.org/10.2165/11591550-000000000-00000] [PMID: 22480381]
[41]
PRISMA-P (Preferred reporting items for systematic review and meta-analysis protocols) 2015 Checklist: Recommended items to address in a systematic review protocol* section and topic item no checklist item. [Online: http://www.prisma-statement.org/docu- ments/PRISMA-P-checklist.pdf] [Accessed February 7, 2019].
[42]
Tarantino, M.D.; Fogarty, P.; Mayer, B.; Vasey, S.Y.; Brainsky, A. Efficacy of eltrombopag in management of bleeding symptoms associated with chronic immune thrombocytopenia. Blood Coagul. Fibrinolysis, 2013, 24(3), 284-296.
[http://dx.doi.org/10.1097/MBC.0b013e32835fac99] [PMID: 23492914]
[43]
Zeng, Y.; Duan, X.; Xu, J.; Ni, X. TPO receptor agonist for chronic idiopathic thrombocytopenic purpura. Cochrane Database Syst Rev; Duan, X., Ed.; , 2011, 7, p. CD008235.
[http://dx.doi.org/10.1002/14651858.CD008235.pub2]
[44]
Zhang, Y.; Kolesar, J.M. Eltrombopag: An oral thrombopoietin receptor agonist for the treatment of idiopathic thrombocytopenic purpura. Clin. Ther., 2011, 33(11), 1560-1576.
[http://dx.doi.org/10.1016/j.clinthera.2011.10.004] [PMID: 22054810]
[45]
Elgebaly, A.S.; Ashal, G.E.; Elfil, M.; Menshawy, A. Tolerability and efficacy of eltrombopag in chronic immune thrombocytopenia: Meta-Analysis of Randomized Controlled Trials. Clin. Appl. Thromb. Hemost., 2017, 23(8), 928-937.
[http://dx.doi.org/10.1177/1076029616663849] [PMID: 27572890]
[46]
Meta-analysis - Eltrombopag - Full Text View - ClinicalTrials.gov. [Online: https://clinicaltrials.gov/ct2/show/NCT01235988? term=eltrombopag&draw=2&rank=102 ], [Accessed: August 16, 2018].
[47]
Favier, R.; Feriel, J.; Favier, M.; Denoyelle, F.; Martignetti, J.A. First successful use of eltrombopag before surgery in a child with MYH9-related thrombocytopenia. Pediatrics, 2013, 132(3), e793-e795.
[http://dx.doi.org/10.1542/peds.2012-3807] [PMID: 23940247]
[48]
Gerrits, A.J.; Leven, E.A.; Frelinger, A.L., III; Brigstocke, S.L.; Berny-Lang, M.A.; Mitchell, W.B.; Revel-Vilk, S.; Tamary, H.; Carmichael, S.L.; Barnard, M.R.; Michelson, A.D.; Bussel, J.B. Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia. Blood, 2015, 126(11), 1367-1378.
[http://dx.doi.org/10.1182/blood-2014-09-602573] [PMID: 26224646]
[49]
Desborough, M.; Hadjinicolaou, A.V.; Chaimani, A. Alternative agents to prophylactic platelet transfusion for preventing bleeding in people with thrombocytopenia due to chronic bone marrow failure: A meta-analysis and systematic review. Cochrane Database of Systematic Reviews; Desborough, M., Ed.; John Wiley & Sons, Ltd: Chichester, UK, 2016.
[http://dx.doi.org/10.1002/14651858.CD012055]
[50]
Zhang, X.; Chuai, Y.; Nie, W.; Wang, A.; Dai, G. Thrombopoietin receptor agonists for prevention and treatment of chemotherapy-induced thrombocytopenia in patients with solid tumours. Cochrane Database Syst. Rev., 2017, 11, CD012035.
[http://dx.doi.org/10.1002/14651858.CD012035.pub2] [PMID: 29178132]

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