Role Of Eltrombopag Research Articles

Aplastic Anemia with Thrombopoietin Gene Mutation Successfully Treated with Romiplostim Monotherapy

Background: Eltrombopag and romiplostim are thrombopoietin-receptor agonists (TPO-RA), which are approved globally for the treatment of immune thrombocytopenia. However, thrombopoietin (TPO) is not just a regulator of megakaryocyte expansion but is also a vital cytokine for hematopoietic stem cell maintenance, supporting all cell lines. While the role of eltrombopag has already been established in aplastic anemia (AA) and is recommended in guidelines, evidence regarding romiplostim in AA is gradually emerging. Here, we narrate the successful treatment of AA with romiplostim. Clinical Description: A 6-year-old girl born out of third-degree consanguineous marriage, presented with pancytopenia without hepatosplenomegaly nor lymphadenopathy. Management and Outcome: Bone marrow was hypocellular. Etiological workup for bone marrow failure syndrome was unremarkable, confirming primary AA. She received blood products and intravenous immunoglobulin. Clinical exome sequencing showed homozygous mutation of the TPO gene, following which a trial of romiplostim, a TPO-RA, was given. Her cell lines improved dramatically, so she was continued on romiplostim maintenance therapy. The child soon became transfusion free and is asymptomatic currently after 2½ years, since diagnosis. Conclusion: Romiplostim, a TPO-RA, can be a potential therapeutic option, as monotherapy, in children with AA associated with TPO loss-of-function mutation. The treatment seems to be promising as it is well tolerated and economical.

Role of eltrombopag in severe aplastic anemia treatment in children

Hematopoietic stem cell transplantation (HSCT) with a matched sibling donor is the first-line therapy for pediatric aplastic anemia (AA). Whether to perform an alternative HSCT or use immunosuppressive therapy (IST) including anti-thymocyte globulin (ATG) is still unclear if suitable donor is not available. IST with concomitant eltrombopag, a thrombopoietin receptor agonist, shows a good response in adult.1 However, data of eltrombopag is limited in pediatric with low prevalence AA, showing equivocal result.

Healthcare resource use and direct costs in severe aplastic anemia (SAA) patients before and after treatment with eltrombopag

Purpose: This study evaluated healthcare resource utilization (HCRU), and direct costs among severe aplastic anemia (SAA) patients treated with eltrombopag (EPAG) using US claims data.Methods: This retrospective, real-world claims database study identified SAA patients aged ≥2 years treated with EPAG who initiated any SAA treatment between 1 July 2014 and 31 December 2017 (identification period) using the Truven MarketScan databases. A subset of 82 patients treated with EPAG during the identification period were evaluated for all-cause and SAA-related HCRU and direct costs as well as blood transfusion 1 month before EPAG initiation (baseline) and at Month 6 after EPAG initiation (follow-up period).Results: The average patient age was 50.8 (SD = 20.6) years old, predominantly female (n = 43, 52.4%), and had a mean CCI at baseline of 1.1 (SD = 1.7). Hospitalizations, and ER, office, and outpatient visits were significantly lower at Month 6 after EPAG initiation compared with 1 month before EPAG initiation (p < .05 for all four all-cause HCRU and SAA-related hospitalizations). An almost two-fold decrease in reliance on biweekly blood transfusions was observed: 1.0 at weeks 1–2 to 0.5 at Month 6 after EPAG initiation. Although prescription costs (mean [SD]) were significantly higher at Month 6 after EPAG initiation compared with 1 month before EPAG initiation (difference of $11,045 USD [SD = $18,801]), these increases were offset by savings in direct costs. Overall, a mean reduction in total all-cause costs of $29,391 USD [SD = $137,770] was reported at Month 6 after EPAG initiation due to substantial reductions in hospitalization ($40,060 USD [SD = $123,198]) and outpatient visits ($2,043 USD [SD = $25,264]).Conclusion: All-cause and SAA-related HCRU were reduced following EPAG treatment. Prescription costs were higher following treatment; however, these costs were generally offset by reductions in direct costs. These results provide real-world evidence around the role of EPAG in SAA treatment.

Safety and tolerability of eltrombopag versus placebo for treatment of thrombocytopenia in patients with advanced myelodysplastic syndromes or acute myeloid leukaemia: a multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial

Patients with myelodysplastic syndrome or acute myeloid leukaemia who are thrombocytopenic and unable to receive disease-modifying therapy have few treatment options. Platelet transfusions provide transient benefit and are limited by alloimmunisation. Eltrombopag, an oral thrombopoietin receptor agonist, increases platelet counts and has preclinical antileukaemic activity. We aimed to assess the safety and tolerability of eltrombopag for the treatment of thrombocytopenia in adult patients with advanced myelodysplastic syndrome, secondary acute myeloid leukaemia after myelodysplastic syndrome, or de-novo acute myeloid leukaemia. We did this multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial at 37 centres in ten countries in Europe, east Asia, and the Americas. Patients aged 18 years or older who had relapsed or refractory disease or were ineligible for standard treatments; had platelet counts of less than 30 × 10(9) platelets per L; had 10-50% bone-marrow blasts; or were platelet transfusion dependent were randomly assigned (2:1), via a telephone-based interactive voice-response system (GlaxoSmithKline Registration and Medication Ordering System) with a permuted-block randomisation schedule (block size of three), to receive once-daily eltrombopag or matching placebo dose adjusted from 50 mg to a maximum dose of 300 mg. Randomisation was stratified by presence of poor-prognosis (complex) karyotype (presence of at least three abnormalities, or chromosome 7 abnormalities, vs absence) and bone-marrow blast count (<20% vs ≥20%). Patients and study personnel were masked to treatment allocation. The primary endpoint was safety and tolerability, including adverse events, non-haematological laboratory grade 3-4 toxic effects, and changes in bone-marrow blast counts from baseline. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00903422. Between May 14, 2009, and May 9, 2013, we randomly assigned 98 patients to receive either eltrombopag (n=64) or placebo (n=34). 63 (98%) patients in the eltrombopag group and 32 (94%) patients in the placebo group had adverse events. The most common adverse events were pyrexia (27 [42%] vs 11 [32%]), nausea (20 [31%] vs 7 [21%]), diarrhoea (19 [30%] vs 6 [18%]), fatigue (16 [25%] vs 6 [18%]), decreased appetite (15 [23%] vs 5 [15%]), and pneumonia (14 [22%] vs 8 [24%]). Drug-related adverse events of grade 3 or higher were reported in six (9%) patients in the eltrombopag group and four (12%) patients in the placebo group. Increases in the proportion of peripheral blasts did not differ significantly between groups. Haemorrhage of grade 3 or higher was reported in ten (16%) patients given eltrombopag and nine (26%) patients given placebo. 21 (33%) patients receiving eltrombopag and 16 (47%) patients receiving placebo died while on treatment. No deaths in patients receiving eltrombopag and two deaths in patients receiving placebo were regarded as treatment related. Post-baseline bone-marrow examinations were done in 40 (63%) patients in the eltrombopag group and 17 (50%) patients in the placebo group. The most common reason for no examination was death before the scheduled 3 month assessment. There were no differences between median bone-marrow blast counts or proportions of peripheral blasts between groups. Eltrombopag doses up to 300 mg daily had an acceptable safety profile in patients with advanced myelodysplastic syndrome or acute myeloid leukaemia. The role of eltrombopag in these patients warrants further investigation. GlaxoSmithKline.

Eltrombopag therapy in newly diagnosed steroid non-responsive ITP patients

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterised by isolated thrombocytopenia (peripheral blood platelet count <100 × 10(9)/L) in the absence of other causes or disorders that may be associated with thrombocytopenia. The upfront treatment in newly diagnosed ITP patients is steroids; however, about one-third patients do not respond, and require other treatment, including IVIg, anti-D, or splenectomy. Previous studies have shown decreased platelet production in some ITP patients, aside from the evidence of enhanced platelet destruction. Thrombopoietin receptor agonists (TPO-RA), such as eltrombopag have been shown to provide good response in steroid non-responsive chronic ITP patients. We have studied response to eltrombopag in 25 newly diagnosed steroid non-responsive ITP patients; 80 % patients showed response at the end of 1 month, and 76 % sustained response at the end of 3 months. The platelet count rose from a mean value of 17.5 ± 3.6-152.5 ± 107.9 × 10(9)/L at the end of 1 month. Our results suggest a possible role of eltrombopag in newly diagnosed steroid non-responsive ITP patients. However, our study is limited in that it is a single-centre study, with a small sample size, and lacks a long-term safety profile. Our findings highlight the potential value of a larger prospective study on the upfront use of TPO-RA in patients of ITP.

Use of eltrombopag in thrombocytopenia of liver disease

Second generation thrombopoietin agonists including eltrombopag and romiplostim act on the thrombopoietin receptor to increase the megakaryocyte production. These agents were needed as use of first generation recombinant products was associated with formation of autoantibodies. Eltrombopag is an oral thrombopoietin agonist found effective in raising platelet counts in patients with immune thrombocytopenia. The drug has now been found to be useful in raising platelet counts in thrombocytopenia related to liver disease including cirrhosis and chronic viral hepatitis. Although the drug may help enable adequate interferon therapy in patients with HCV infection and help carry out invasive procedures in patients with cirrhosis, concerns have been raised of possible thrombotic complications including portal vein thrombosis. Randomized trials have shown that use of eltrombopag concomitant with pegylated interferon and ribavirin increased the chances of sustained virologic response while decreasing the dose reductions of interferon. The data on use of romiplostim in these clinical indications is also emerging. However, in the future, availability of interferon free regimens is likely to decrease the use of eltrombopag for enabling antiviral therapy. The review discusses the role of eltrombopag in management of liver disease related thrombocytopenia in wake of recent data as also the dosage, precautions and adverse effects associated with its use.

The role of eltrombopag in the management of hepatitis C virus-related thrombocytopenia

Eltrombopag is a 2nd generation thrombopoietin-receptor agonist. It binds with the thrombopoietin-receptors found on the surfaces of the megakaryocytes & increases platelet production. Many recent studies have suggested a potential role for this novel agent in the treatment of thrombocytopenia associated with hepatitis-C infection. Studies have shown that adjunct treatment with Eltrombopag can help avoid dose reductions/withdrawals of pegylated interferon secondary to thrombocytopenia. It may also have a role in priming up platelet levels to help initiate antiviral therapy. Similarly, chronic liver disease patients with thrombocytopenia who need to undergo an invasive procedure may be potential candidates for short two-week courses of eltrombopag in the periprocedural period to help reduce the risk of bleeding. Besides the price (deemed very expensive and probably not cost-effective), there are some legitimate concerns about the safety profile of this novel agent (most importantly, portal vein thrombosis, bone marrow fibrosis and hepatotoxicity). In this article, the potential role of eltrombopag in the context of hepatitis C virus (HCV)-related thrombocytopenia is reviewed. To write this article, a MEDLINE search was conducted (1990 to November 2012) using the search terms “eltrombopag,” “HCV,” and “thrombocytopenia.”