Sequential treatment with thrombopoietin-receptor agonists (TPO-RAs) in immune thrombocytopenia (ITP): experience in our center

Gonzalez, Karla Javier; Zuluaga, Sebastian Ortiz; DaRos, Carolina Villegas; Rodríguez, P.

doi:10.1007/s00277-016-2896-3

Cited by 8 publications

(8 citation statements)

References 10 publications

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“…We identified 18 journal publications that reported retrospective findings in 401 patients with ITP who switched their TPO-RA therapy (Table 1). 21–38 In a pooled analysis of these studies, lack of efficacy was identified as the primary reason for switching in 58% of patients (172/295). Non-efficacy-related reasons for switching included adverse events (AEs), patient preference, and platelet count fluctuations.…”

Section: Switching: Clinical Datamentioning

confidence: 99%

Switching thrombopoietin receptor agonist treatments in patients with primary immune thrombocytopenia

González‐Porras

Godeau

Carpenedo

2019

Therapeutic Advances in Hematology

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Primary immune thrombocytopenia (ITP) is a bleeding disorder that conventionally has been treated with steroids or other immunosuppressive treatments. The introduction of thrombopoietin receptor agonists (TPO-RAs), which increase platelet production, dramatically changed the treatment landscape for ITP by providing patients with well-tolerated, long-term treatment options. Two TPO-RAs, eltrombopag and romiplostim, have been approved in the United States and European Union for the treatment of ITP. Some patients do not benefit from the first TPO-RA they receive, so it is assumed that the alternate TPO-RA would have the same outcome. However, eltrombopag and romiplostim have distinct pharmacodynamic and pharmacokinetic properties and may have different tolerability and efficacy in individual patients with ITP. Published retrospective studies showed that >75% of patients who switched to the alternate TPO-RA maintained or achieved a response with the new treatment. Notably, most patients who switched due to lack of efficacy with the first TPO-RA responded to the alternate TPO-RA, which demonstrates an absence of cross-resistance between the two drugs. Therefore, switching to the alternate TPO-RA if the first TPO-RA fails to demonstrate a response should be considered before the use of a less-preferable option.

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Section: Switching: Clinical Datamentioning

confidence: 99%

Switching thrombopoietin receptor agonist treatments in patients with primary immune thrombocytopenia

González‐Porras

Godeau

Carpenedo

2019

Therapeutic Advances in Hematology

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“…Cumulative results from studies of adult patients initially treated with romiplostim and transitioned to eltrombopag after treatment with romiplastim failed showed a 74% success rate with sequential TPO-RA therapy. 41 Adults who initially experienced treatment failure with eltrombopag had an 88% response rate when they were transitioned to romiplostim. 41 …”

Section: Choosing a Thrombopoietin Agonistmentioning

confidence: 99%

“…41 Adults who initially experienced treatment failure with eltrombopag had an 88% response rate when they were transitioned to romiplostim. 41 …”

Section: Choosing a Thrombopoietin Agonistmentioning

confidence: 99%

Eltrombopag for use in children with immune thrombocytopenia

2018

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Eltrombopag is currently the only US Food and Drug Administration–approved thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia (ITP) in children. This oral, once-per-day therapy has shown favorable efficacy and adverse effect profiles in children. Two multicenter, double-blind, placebo controlled clinical trials (PETIT [Efficacy and Safety Study of Eltrombopag in Pediatric Patients With Thrombocytopenia From Chronic Idiopathic Thrombocytopenic Purpura (ITP)] and PETIT2 [Study of a New Medication for Childhood Chronic Immune Thrombocytopenia (ITP), a Blood Disorder of Low Platelet Counts That Can Lead to Bruising Easily, Bleeding Gums, and/or Bleeding Inside the Body]) demonstrated efficacy in raising platelet counts, reducing bleeding, and reducing the need for concomitant ITP therapies with relatively few adverse effects. The most commonly reported drug-related adverse effects include headache, nausea, and hepatobiliary laboratory abnormalities. Long-term safety data in children are limited, and studies in adults have not revealed a clinically significant increased incidence of thrombosis, marrow fibrosis, or cataract formation. Eltrombopag has also been approved for treating refractory severe aplastic anemia (AA) and has potential for expanded use in ITP and severe AA as well as in other conditions associated with thrombocytopenia.

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“…Some observations suggest that eltrombopag and romiplostim stimulate platelet production by different mechanisms. For instance, some patients with ITP who are not responsive to romiplostim may respond to eltrombopag, and vice versa . Moreover, a recent in vitro study suggested that romiplostim mainly promotes proliferation of immature megakaryocytes through disproportionate activation of AKT with respect to the extracellular signal‐regulated kinase 1/2 signaling pathway, whereas eltrombopag sustains both proliferation and differentiation of megakaryocytes through balanced activation of both of these pathways (Fig.…”

Section: Tpo‐rasmentioning

confidence: 99%

Thrombopoietin receptor agonists in hereditary thrombocytopenias

Rodeghiero

Pecci

Balduini

2018

Journal of Thrombosis and Haemostasis

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Hereditary thrombocytopenias (HTPs) constitute a heterogeneous group of diseases characterized by a reduction in platelet count and a potential bleeding risk. As a result of advances in diagnostic methods, HTPs are increasingly being identified, and appear to be less rare than previously thought. Most HTPs do not have effective treatments, except for platelet transfusion when bleeding occurs and in preparation for procedures associated with a risk of bleeding. Preliminary clinical evidence suggests that thrombopoietin receptor agonists (TPO-RAs) with an established use in the treatment of certain acquired thrombocytopenias are well tolerated and provide clinical benefits in patients with some forms of HTP. These drugs may therefore be considered for the treatment of HTPs in clinical practice. However, caution and close monitoring are recommended, owing to the absence of long-term safety data and the potential risks posed by prolonged bone marrow stimulation in certain HTPs. In this review, we summarize the available clinical data on TPO-RAs in the treatment of HTPs, and discuss their use in patients with these disorders. We believe that TPO-RAs will play a major role in the treatment of HTPs, particularly myosin heavy chain 9-related disease, Wiskott-Aldrich syndrome, X-linked thrombocytopenia, and thrombocytopenia caused by THPO mutations.

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Sequential treatment with thrombopoietin-receptor agonists (TPO-RAs) in immune thrombocytopenia (ITP): experience in our center

Cited by 8 publications

References 10 publications

Switching thrombopoietin receptor agonist treatments in patients with primary immune thrombocytopenia

Switching thrombopoietin receptor agonist treatments in patients with primary immune thrombocytopenia

Eltrombopag for use in children with immune thrombocytopenia

Thrombopoietin receptor agonists in hereditary thrombocytopenias

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