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Ferrata Storti Foundation
Haematologica 2018 Volume 104(6):1112-1123
Thrombopoietin receptor agonists: ten years later
Waleed Ghanima,1,2 Nichola Cooper,3 Francesco Rodeghiero,4 Bertrand Godeau5 and James B. Bussel6
1Departments of Medicine, Hematology-Oncology and Research, Østfold Hospital Trust, Norway; 2Department of Hematology, Institute of Clinical Medicine, University of Oslo, Norway; 3Department of Medicine, Hammersmith Hospital, Imperial College, London, UK; 4Hematology Project Foundation and Department of Cell Therapy and Hematology, S. Bortolo Hospital, Vicenza, Italy; 5Department of Internal Medicine, Henri Mondor University Hospital, Assistance Publique-Hopitaux de Paris, UPEC, Créteil, France and 6Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA
ABSTRACT
TThe two thrombopoietin receptor agonists (TPO-RA), eltrombopag and romiplostim, were licensed in the US for treatment of immune thrombocytopenia (ITP) in 2008 and, since then, their use has pro- gressively increased around the world; they are currently used in more than 100 countries. The six largest randomized controlled trials conducted in ITP have used one of these two agents. All studies have demonstrated a platelet response rate between 50-90%, depending on the criteria used, with good safety and tolerability. TPO-RA were shown to be effective in reducing bleeding and the need for concomitant or rescue medication. Many other investigations of their mechanism of effect, prospective and retrospective trials, and studies focusing on toxicity have been performed widening our knowledge of these two agents. Initial concerns on issues such as myelofibrosis have not been confirmed. Only a small number of patients develop moderate-severe reticulin fibrosis and/or collagen fibro- sis; however, these are usually reversed after discontinuation of TPO-RA. Studies indicate, however, that TPO-RA may increase the risk of venous thromboembolism. Both TPO-RA are currently approved in patients with chronic ITP aged >1-year who are refractory to at least one other treat- ment. Eltrombopag has acquired two additional indications: severe aplas- tic anemia refractory to first-line treatment and hepatitis C patients under- going treatment with interferon-ribavirin. Despite these wide-ranging studies, important questions still need to be answered. This summary review on TPO-RA will summarize what is known regarding efficacy in ITP, evaluate safety concerns in more depth, and focus on the questions that remain.
Introduction
Over the last 20 years, and before the regular availability of thrombopoietin receptor agonists (TPO-RA), the most commonly used second-line treatments for patients with immune thrombocytopenia (ITP) were splenectomy and rituximab. Both options have the potential to provide a cure. However, long-term responses are not completely satisfactory (60% after splenectomy and only 20% 2-5 year long-term responses after rituximab).1,2 Adverse events following these interven- tions are also significant, if uncommon: post-operative morbidity and increased risk of infections and thromboembolism (TE) after splenectomy, and very rare cases of progressive multifocal leukoencephalopathy (PML) and slight increased infectious rates after rituximab.3
The two TPO-RA, romiplostim and eltrombopag, represent a completely differ- ent approach to ITP; they both have a very good chance of supporting the platelet count with undemanding daily or weekly treatment. Their goal is to support the patient’s platelet count until adequate levels are achieved and treatment is no
Correspondence:
WALEED GHANIMA
waleed.ghanima@SO-HF.no
Received: November 28, 2018. Accepted: March 11, 2019. Pre-published: May 9, 2019.
doi:10.3324/haematol.2018.212845
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/6/1112
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