Eltrombopag in immune thrombocytopenia: efficacy review and update on drug safety

Abstract

Immune thrombocytopenia (ITP) is an autoimmune disorder that induces a decrease in the number of circulating platelets due to spleen destruction and inability of megakaryocytes to restore normal counts. Immunosuppressive therapy with glucocorticoid drugs constitutes the first line of treatment. However, lack of response to these agents is not uncommon, and the management of refractory patients is a matter of controversy. In fact, day-to-day clinical practice shows that, in spite of the current guidelines, splenectomy, which is currently considered a suitable second-choice therapy, is being replaced by treatment with thrombopoietin receptor agonists. These boost platelet production by megakaryocytes. The use of one of these, namely eltrombopag, has been permitted for ITP patients refractory to first-line drugs or splenectomy, for the last 10 years. This review summarizes the experience reported using eltrombopag in ITP, paying attention to efficacy and safety. Results from clinical trials will be discussed, and studies performed in the course of daily clinical practice will also be reviewed, as these are useful to assess the potential of the drug in real-world settings. The management of adverse events and the use of eltrombopag in particular situations will also be covered. The experience reported so far permits us to suggest that eltrombopag efficiently induces recovery of platelet counts. Furthermore, recent papers have demonstrated that a sustained response after discontinuation, initially thought to be problematic, may be possible in a nonnegligible number of cases. The safety profile is satisfactory, although patients presenting with thromboembolism risk factors should be treated with caution until the eltrombopag-associated prothrombotic risk is fully established. In summary, although larger studies are still needed to clarify some issues, eltrombopag may be a useful alternative tool for ITP patients refractory to conventional medical management or splenectomy.

Thrombopoietin Receptor Agonists for Severe Thrombocytopenia after Allogeneic Stem Cell Transplantation: Experience of the Spanish Group of Hematopoietic Stem Cell Transplant

“…Romiplostim and eltrombopag are currently available thrombopoietin receptor agonists (TPO-RAs) that stimulate platelet production. Eltrombopag is approved for the treatment of refractory immune thrombocytopenia [6,7] and thrombocytopenia secondary to hepatitis C infection [8]. Recently, it has been associated with multilineage responses in some patients with refractory severe aplastic anemia [9], supporting the idea that it may directly stimulate the few surviving HSCs [10].…”

Treatment efficacy for adult persistent immune thrombocytopenia: a systematic review and network meta‐analysis

“…Romiplostim is a peptide TPO‐RA which binds to the extracellular domain of thrombopoietin receptor, activates JAK‐STAT, MAPK and PI3K‐AKT pathways, stimulates proliferation and maturation of megakaryocytes, and inhibits apoptosis of megakaryocytes; resulting in increased platelet production (Vishnu & Aboulafia, ; Cooper, ). Eltrombopag is a non‐peptide TPO‐RA that binds to the transmembrane domain of thrombopoietin receptor and activates the same pathways as romiplostim (Cooper, ; Gonzalez‐Porras & Bastida, ). Being less specific to ITP than the TPO‐RAs, rituximab is a monoclonal antibody which binds to the surface of CD20‐positive B lymphocytes and induces B‐cell depletion (Braendstrup et al , ).…”

Per-head cost of patients responding to eltrombopag and rituximab in the treatment of primary immune thrombocytopenia in Spain.

“…The rst option permits lasting responses after a short treatment, with approximately 60% initial responses and a third of patients in remission after 1 year [11][12][13][14][15][16]. The second involves long-term treatments, but with high response rates (75-95%), and it has fewer side effects than rituximab and the potential of drug discontinuation [11,[17][18][19][20][21][22]. Hence, those formerly considered third-line treatments have become extensively used [23].…”