Abstract
Eltrombopag (Promacta®; Revolade®) is an orally active thrombopoietin receptor agonist recently approved in the USA and the EU for use in paediatric patients aged ≥1 year with chronic immune thrombocytopenia (ITP) who have had an insufficient response or are refractory to other ITP treatments (e.g. corticosteroids, immunoglobulins or splenectomy). The efficacy of 7 or 13 weeks’ therapy with oral eltrombopag (up to 75 mg/day) was compared with that of placebo in patients aged 1–17 years with previously treated chronic ITP in randomized, double-blind, multicentre phase II and III trials (PETIT and PETIT-2). In these trials, the platelet response rate (primary endpoint of PETIT) and the sustained platelet response rate (primary endpoint of PETIT-2) were significantly higher with eltrombopag than with placebo. A clinical benefit was shown by a reduction in the need for rescue therapy with eltrombopag versus placebo in both trials and a reduction of clinically significant bleeding in PETIT. During longer-term therapy (open-label treatment period for ≥24 weeks), eltrombopag maintained platelet counts above 50 × 109/L in the majority of patients and approximately one-half of patients were able to reduce or discontinue concurrent ITP drugs. Eltrombopag was generally well tolerated. Current evidence suggests that eltrombopag is a valuable addition to the limited treatment options available for the management of chronic ITP in paediatric patients with an inadequate response to first-line therapies.
Similar content being viewed by others
References
Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386–93.
Labarque V, Van Geet C. Clinical practice: immune thrombocytopenia in paediatrics. Eur J Pediatr. 2014;173(2):163–72.
Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190–207.
Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115(2):168–86.
Garnock-Jones KP. Eltrombopag: a review of its use in treatment-refractory chronic primary immune thrombocytopenia. Drugs. 2011;71(10):1333–53.
GlaxoSmithKline. Promacta® (eltrombopag): US prescribing information. 2015. https://www.pharma.us.novartis.com/product/pi/pdf/promacta.pdf. Accessed 17 Mar 2016.
European Medicines Agency. Revolade™ (eltrombopag): EU summary of product characteristics. 2016. http://www.ema.europa.eu. Accessed 26 Apr 2016.
Burness CB. Eltrombopag: a review of its use in the treatment of thrombocytopenia in patients with chronic hepatitis C. Drugs. 2014;74(16):1961–71.
McCormack PL. Eltrombopag: a review of its use in patients with severe aplastic anaemia. Drugs. 2015;75(5):525–31.
Erickson-Miller CL, Delorme E, Tian SS, et al. Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist. Stem Cells. 2009;27(2):424–30.
Jenkins JM, Williams D, Deng Y, et al. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood. 2007;109(11):4739–41.
Bussel JB, De Miguel PG, Despotovic JM. Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study. Lancet Haematol. 2015;2(8):e315–25.
Grainger JD, Locatelli F, Chotsampancharoen T, et al. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet. 2015;386:1649–58.
Bussel JB, Cheng G, Saleh MN, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007;357(22):2237–47.
Erhardt JA, Erickson-Miller CL, Aivado M, et al. Comparative analyses of the small molecule thrombopoietin receptor agonist eltrombopag and thrombopoietin on in vitro platelet function. Exp Hematol. 2009;37(9):1030–7.
Psaila B, Bussel JB, Linden MD, et al. In vivo effects of eltrombopag on platelet function in immune thrombocytopenia: no evidence of platelet activation. Blood. 2012;119(17):4066–72.
Matthys G, Park JW, McGuire S, et al. Eltrombopag does not affect cardiac repolarization: results from a definitive QTc study in healthy subjects. Br J Clin Pharmacol. 2010;70(1):24–33.
FDA. Clinical pharmacology review. 2015. http://www.fda.gov/. Accessed 17 Mar 2016.
Matthys G, Park JW, McGuire S, et al. Clinical pharmacokinetics, platelet response, and safety of eltrombopag at supratherapeutic doses of up to 200 mg once daily in healthy volunteers. J Clin Pharmacol. 2011;51(3):301–8.
Wire MB, Bruce J, Gauvin J, et al. A randomized, open-label, 5-period, balanced crossover study to evaluate the relative bioavailability of eltrombopag powder for oral suspension (PfOS) and tablet formulations and the effect of a high-calcium meal on eltrombopag pharmacokinetics when administered with or 2 hours before or after PfOS. Clin Ther. 2012;34(3):699–709.
Williams DD, Peng B, Bailey CK, et al. Effects of food and antacids on the pharmacokinetics of eltrombopag in healthy adult subjects: two single-dose, open-label, randomized-sequence, crossover studies. Clin Ther. 2009;31(4):764–76.
Bussel JB, Grainger JD, de Miguel PG, et al. PETIT and PETIT 2: treatment with eltrombopag in 171 children with chronic immune thrombocytopenia (ITP) [abstract]. Blood. 2014;124(21):1450.
Cheng G, Saleh MN, Marcher C, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011;377(9763):393–402.
Grainger JD, Routledge DJM, Kruse A, et al. Thrombopoietin receptor agonists in paediatric ITP patients: long term follow up data in 34 patients [abstract]. Blood. 2014;124(21):4206.
Kuter DJ, Mufti GJ, Bain BJ, et al. Evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim. Blood. 2009;114(18):3748–56.
FDA. Clinical review: Promacta® (eltrombopag) tablets. 2015. http://www.fda.gov/. Accessed 17 Mar 2016 2016.
McGuinn CE, Imahiyerobo A, Thompson M, et al. Safety and efficacy of eltrombopag at escalated doses up to 150 mg in patients with persistent and chronic immune thrombocytopenia (ITP) not responsive to 75 mg [abstract]. Blood. 2013;122(21):3559.
Ghanima W, Geyer JT, Lee CS, et al. Bone marrow fibrosis in 66 patients with immune thrombocytopenia treated with thrombopoietin-receptor agonists: a single-center, long-term follow-up. Haematologica. 2014;99(5):937–44.
Ghadaki B, Nazi I, Kelton JG, et al. Sustained remissions of immune thrombocytopenia associated with the use of thrombopoietin receptor agonists. Transfusion. 2013;53(11):2807–12.
Mahevas M, Fain O, Ebbo M, et al. 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.
Amgen Inc. Nplate® (romiplostim), for subcutaneous injection: US prescribing information. 2014. http://www.nplate.com/. Accessed 17 Mar 2016.
European Medicines Agency. Nplate (romiplostim): EU summary of product characteristics. 2015. http://www.ema.europa.eu. Accessed 17 Mar 2016.
Bussel JB, Buchanan GR, Nugent DJ, et al. A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia. Blood. 2011;118(1):28–36.
Elalfy MS, Abdelmaksoud AA, Eltonbary KY. Romiplostim in children with chronic refractory ITP: randomized placebo controlled study. Ann Hematol. 2011;90(11):1341–4.
Gonzalez-Porras JR, Mingot-Castellano ME, Andrade MM, et al. Use of eltrombopag after romiplostim in primary immune thrombocytopenia. Br J Haematol. 2015;169(1):111–6.
Mori M, Kato M, Koh K, et al. Successful switching from eltrombopag to romiplostim in a pediatric patient with refractory chronic ITP. Rinsho Ketsueki. 2015;56(5):511–3.
Acknowledgments
During the peer review process, the manufacturer of eltrombopag was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
The preparation of this review was not supported by any external funding.
Conflicts of interest
Celeste B. Burness, Gillian Keating and Karly P. Garnock-Jones are salaried employee of Adis/Springer, are responsible for the article content and declare no relevant conflicts of interest.
Additional information
The manuscript was reviewed by: D. B. Cines, Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; J Despotovic, Texas Children’s Hematology Center, Baylor College of Medicine, Houston, TX, USA; J. Grainger, Faculty of Medical and Human Sciences, University of Manchester; Royal Manchester Children’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; F. Rodeghiero, Hematology Department, S Bortolo Hospital, Vincenza, Italy, J. Sevilla, Hemato-Oncología Pediátrica Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Rights and permissions
About this article
Cite this article
Burness, C.B., Keating, G.M. & Garnock-Jones, K.P. Eltrombopag: A Review in Paediatric Chronic Immune Thrombocytopenia. Drugs 76, 869–878 (2016). https://doi.org/10.1007/s40265-016-0581-4
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40265-016-0581-4