Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: A randomised, double-blind, placebo-controlled trial

Weill-Cornell Medical College of Cornell University, New York, NY, USA.
The Lancet (Impact Factor: 45.22). 03/2009; 373(9664):641-8. DOI: 10.1016/S0140-6736(09)60402-5
Source: PubMed


Eltrombopag is an oral, non-peptide, thrombopoietin-receptor agonist that stimulates thrombopoiesis, leading to increased platelet production. This study assessed the efficacy, safety, and tolerability of once daily eltrombopag 50 mg, and explored the efficacy of a dose increase to 75 mg.
In this phase III, randomised, double-blind, placebo-controlled study, adults from 63 sites in 23 countries with chronic idiopathic thrombocytopenic purpura (ITP), platelet counts less than 30 000 per muL of blood, and one or more previous ITP treatment received standard care plus once-daily eltrombopag 50 mg (n=76) or placebo (n=38) for up to 6 weeks. Patients were randomly assigned in a 2:1 ratio of eltrombopag:placebo by a validated randomisation system. After 3 weeks, patients with platelet counts less than 50 000 per microL could increase study drug to 75 mg. The primary endpoint was the proportion of patients achieving platelet counts 50 000 per microL or more at day 43. All participants who received at least one dose of their allocated treatment were included in the analysis. This study is registered with, number NCT00102739.
73 patients in the eltrombopag group and 37 in the placebo group were included in the efficacy population and were evaluable for day-43 analyses. 43 (59%) eltrombopag patients and six (16%) placebo patients responded (ie, achieved platelet counts >/=50 000 per microL; odds ratio [OR] 9.61 [95% CI 3.31-27.86]; p<0.0001). Response to eltrombopag compared with placebo was not affected by predefined study stratification variables (baseline platelet counts, concomitant ITP drugs, and splenectomy status) or by the number of previous ITP treatments. Of the 34 patients in the efficacy analysis who increased their dose of eltrombopag, ten (29%) responded. Platelet counts generally returned to baseline values within 2 weeks after the end of treatment. Patients receiving eltrombopag had less bleeding at any time during the study than did those receiving placebo (OR 0.49 [95% CI 0.26-0.89]; p=0.021). The frequency of grade 3-4 adverse events during treatment (eltrombopag, two [3%]; placebo, one [3%]) and adverse events leading to study discontinuation (eltrombopag, three [4%]; placebo, two [5%]), were similar in both groups.
Eltrombopag is an effective treatment for managment of thrombocytopenia in chronic ITP.

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    • "As the platelets in ITP are freshly out of the bone marrow and quite active, swift increases in platelet count may cause thrombosis [10]. Autoimmune mechanisms are responsible for platelet destruction and decreased release from megakaryocytes, so immunomodulatory drugs such as steroids,IVIG, vincristine, and danazol can evert the mechanism and can cause an increased risk of thrombosis.Eltrombopag, an oral thrombopoietin receptor antagonist, is a safe and efficient novel agent in resistant and relapsed ITP [11] [12]. Elevated risk of thrombosis has been reported with eltrombopag, especially with known thrombophilia and chronic liver disease [13]. "
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    ABSTRACT: Immune trombocytopenia is an autoimmune disease characterised by abnormal platelet destruction. Corticosteroids and intravenous immune globulin are main first line treatment options. Splenectomy is a preferred second line treatment option for unresponsive patients at many centers. Secondary thrombocytosis is a possible complication awaiting this group of patients after splenectomy. Here, we present a case of myocardial infarction at a patient who had undergone splenectomy for ITP, which is a rare event seen with secondary thrombocytosis due to splenectomy.
    Full-text · Article · Aug 2015
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    • "TPO agonists are used for thrombocytopenia refractory to other therapies such as corticosteroids, intravenous immunoglobulin (IV Ig), single agent rituximab and splenectomy or when splenectomy is contraindicated.67,68 It has been suggested that these therapeutic modules should be used when a durable response is not obtained with other therapies and the platelet count continues to decline below 50,000. "
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    ABSTRACT: CLL has been defined as presence of more than 5000 small mature appearing monoclonal B lymphocytes with a specific immunophenotype in peripheral blood. It is a well-known fact that CLL is associated with autoimmune cytopenias. CLL cells are CD5+ B lymphocytes, and usually are not the “guilty” cells which produce autoantibodies. T cell defect is another characteristic of CLL and the total number of T cells is increased, and there is inversion of the CD4/CD8 ratio. Autoimmune hemolytic anemia (AIHA) is the most common autoimmune complication of CLL and has been reported in 10–25% of CLL patients. However, the stage-adjusted estimated rate of AIHA in CLL is about 5%. Conversely, CLL is three times more common in patients who present with AIHA. Direct agglutinin test (DAT) is positive in 7–14% of CLL patients but AIHA may also occur in DAT negative patients. Autoimmune thrombocytopenia (AIT) is the second most common complication of CLL and has been reported in 2–3% of patients. DAT is positive in AIT but presence of antiplatelet antibodies is neither diagnostic nor reliable. Autoimmune neutropenia (AIN) and pure red cell aplasia (PRCA) are very rare complications of CLL and like other autoimmune complications of CLL may occur at any clinical stage. It is believed that most case reports of AIN and PRCA in CLL actually belong to large granular lymphocytic leukemia (LGL). Non-hematologic autoimmune complications of CLL including cold agglutinin disease (CAD), paraneoplastic pemphigus (PNP), acquired angioedema, and anti-myelin associated globulin are rare. Before starting any treatment, clinicians should distinguish between autoimmune cytopenias and massive bone marrow infiltration since autoimmune complications of CLL are not necessarily equal to advanced disease with poor prognosis. According to IWCLL guideline, steroids are the mainstay of treatment of simple autoimmunity. Intravenous immunoglobulin (IVIg), cyclosporine, and rituximab are used in complex, steroid refractory cases. Monotherapy with purine analogues and alkylating agents should be avoided as they may increase CLL associated autoimmune complications.
    Full-text · Article · Nov 2013 · Mediterranean Journal of Hematology and Infectious Diseases
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    • "Both drugs have been demonstrated to be efficacious in resistant ITP patients after splenectomy failure and in those patients resistant, who are not surgical candidates. 42- 44 Romiplostim and eltrombopag have been only occasionally reported in CLL-associated ITP treatment.45–48 Clearly, the splenectomy in CLL- related ITP seems to have a wider role. "
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    ABSTRACT: Autoimmune cytopenias are a frequent complication in CLL, occurring in approximately 5–10% of the patients. The most common manifestation is autoimmune haemolytic anaemia, followed by immune thrombocytopenia and only rarely pure red blood cell aplasia or autoimmune granulocytopenia. Initial treatment is as for the idiopathic autoimmune cytopenias, with most patients responding to conventional corticosteroid therapy. Patients, who do not respond to conventional therapy after 4–6 weeks, should be considered for alternative immunosuppression, monoclonal antibody therapy or splenectomy. While randomized trials demonstrating the benefit of rituximab in CLL-related autoimmune diseases are still lacking, there are considerable data in the literature that provide evidence for its effectiveness. The monoclonal antibody alemtuzumab also displays considerable activity against both the malignant disease and the autoimmune complication in patients with CLL, although at the expense of greater toxicity. A number of new monoclonal antibodies, such as ofatumumab, GA-101, lumiliximab, TRU-016, epratuzumab, and galiximab, are currently investigated in CLL and their activity in CLL-related autoimmune cytopenias should be evaluated in future studies.
    Full-text · Article · Apr 2013 · Mediterranean Journal of Hematology and Infectious Diseases
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