Efficacy and safety of eltrombopag in the first-line therapy of severe aplastic anemia in children

Ma, Jingyao; Fu, Lingling; Li, Sidan; He, Yijie; Yao, Jiafeng; Cheng, Xiaoling; Zhang, Liqiang; Zheng, Jie; Zhang, Rui; Wu, Runhui

doi:10.1080/08880018.2021.1900475

Cited by 14 publications

(27 citation statements)

References 26 publications

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“…Tremblay et al found a CR rate of 58.06% versus a 10% rate among the groups with and without EPAG, respectively. (Fang et al, 2021;Groarke et al, 2021;Jie et al, 2021;Tremblay et al, 2019) As for disease remission, Fang et al described only one patient in the entire study who relapsed within 6 months, compared with none in the IST group; in the work by Jie et al, no relapse was observed within 2 years of observation, in addition to demonstrating an event-free survival in 78.6% of the cases using the EPAG. The difference in mean survival has not been shown to be statistically significant between the different studies.…”

Section: Resultsmentioning

confidence: 99%

“…The difference in mean survival has not been shown to be statistically significant between the different studies. (Fang et al, 2021;Jie et al, 2021) Despite there are known adverse effects after using EPAG, most are shown to be reversible and tolerable. In an American study, the most frequent effect was the elevation of liver enzymes.…”

Section: Resultsmentioning

confidence: 99%

“…In Japan, the most common adverse event was myalgia, followed by hyperbilirubinemia, which is resolved with EPAG dose reduction or brief interruption of the regimen. (Imada et al, 2021;Jie et al, 2021;Tremblay et al, 2019) The adverse effects of EPAG bring additional cost to the system, as they are absent in the GAT + Cyclosporine group, but when compared to the adverse effects of this second group, the EPAG does not add a statistically significant cost. (Tremblay et al, 2019) The costs for the IST with the addition of the EPAG are still an important obstacle to its acquisition by health services financed by the Unified Health System of Brazil.…”

Section: Resultsmentioning

confidence: 99%

“…Non-medical and indirect costs and the fees of the professionals involved, were not evaluated. (Imada et al, 2021;Jie et al, 2021;Saúde, 2010) A theoretical simulation of a typical patient was used as a basis for cost calculation, which would be followed up by a pediatric hematology service in the state of Sergipe, which is as part of Brazil's Unified Health System. Based on the literature, the typical patient is male, 14 years old, weighing 49 kg, without previous immunosuppressive therapy use, with a history of more than 20 blood transfusions, without family history of hematological disease.…”

Section: Methodsmentioning

confidence: 99%

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Estimative of costs of two therapeutic schemes for aplastic anemia among young individuals

Prado

Cipolotti²,

Cerqueira³

2022

RSD

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Introduction: Aplastic anemia (AA) is the deficiency of the production of blood cells, with pancytopenia and hypocellular marrow as a result. Eltrombopag® (EPAG), a synthetic thrombopoietin mimic, showed improvement in bone marrow, CD34 and blood precursor cell counts. Today, it is indicated as first-line therapy, in addition to Immunosuppressive Therapy (IST) with cyclosporine and horse Antithymocyte Globulin (ATG). The aim of this study is to compare costs and results of the main current therapeutic schemes for AA among young individuals. Method: This is a study to estimate costs and results of a therapeutic scheme using EPAG associated with IST and the management of complications in comparison with standard therapy. The protocols used were those of the Ministry of Health and the scheme indicated in the literature for the EPAG. As a basis for calculation, a typical patient was simulated, who would be followed up by a pediatric hematology service in Sergipe, which works as part of the Unified Health System. Result: The cost of Cyclosporine + rabbit ATG treatment for 6 months, based on patient weight, was US$4500. The cost of Cyclosporine + rabbit GAT + EPAG treatment for 6 months was US$182,000. Conclusion: It is concluded, therefore, that drug therapy with EPAG increases the cost of treatment by 40 times. Several studies, however, point to clinical and laboratory gains and increased response rates to the proposed therapy, thus contributing to a better quality of life for a pediatric patient with AA.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Estimative of costs of two therapeutic schemes for aplastic anemia among young individuals

Prado

Cipolotti²,

Cerqueira³

2022

RSD

View full text Add to dashboard Cite

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“…Studies of EPAG with IST as a first-line therapy have been conducted primarily with adults in the past decade, while clinical evidence for the benefit of adding EPAG to standard IST in children remains limited and conflicting (Supplementary Table S1) (12)(13)(14)(15)(16)(17)(18)(19)(20). According to a retrospective study performed by the NIH, it seems that the addition of EPAG to IST did not provide the same benefit in children as that observed in adults with SAA (16).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of eltrombopag with immunosuppressive therapy for children with acquired aplastic anemia

et al. 2023

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BackgroundEltrombopag (EPAG), an oral thrombopoietin receptor agonist (TPO-RA), has been proven to improve the hematologic response without increasing toxic effects as a first-line therapy combined with standard immunosuppressive treatment (IST) in adults with severe aplastic anemia (SAA). Nevertheless, the clinical evidence on the efficacy of EPAG in children with acquired aplastic anemia is limited and controversial.MethodsWe performed a single-center, retrospective study to analyze the clinical outcomes of fifteen patients aged ≤18 years with newly diagnosed acquired SAA who received first-line IST and EPAG (EPAG group) compared with those of forty-five patients who received IST alone (IST group) by propensity score matching (PSM).ResultsThere was no difference in the overall response (OR) rate between the EPAG group and IST group (53.3% vs. 46.7% at 3 months, P = 0.655; 66.7% vs. 57.8% at 6 months, P = 0.543), but the complete response (CR) rate was statistically significant (20.0% vs. 4.4% at 3 months, P = 0.094; 46.7% vs. 13.3% at 6 months, P = 0.012). The median time to achieve a hematological response in the EPAG and IST groups was 105 days and 184 days, respectively. No difference was observed in the event-free survival (EFS) or overall survival (OS) rates.ConclusionAdding EPAG to standard IST as the first-line treatment for children with acquired SAA improved the rapidity of hematological response and the CR rate but did not improve the OR or EFS rates.

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Efficacy, Safety, and Population Pharmacokinetics of Eltrombopag in Children with Different Severities of Aplastic Anemia

Zhang,

Chang,

Zhao

et al. 2024

The Journal of Clinical Pharma

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Eltrombopag was approved as a first‐line treatment for patients older than 2 years old with severe aplastic anemia (SAA). However, data on eltrombopag in children with different types of aplastic anemia (AA), especially non‐severe AA (NSAA), are limited. We performed a prospective, single‐arm, and observational study to investigate eltrombopag's efficacy, safety, and pharmacokinetics in children with NSAA, SAA, and very severe AA (VSAA). The efficacy and safety were assessed every 3 months. The population pharmacokinetic (PPK) model was used to depict the pharmacokinetic profile of eltrombopag. Twenty‐three AA children with an average age of 7.9 (range of 3.0–14.0) years were enrolled. The response (complete and partial response) rate was 12.5%, 50.0%, and 100.0% after 3, 6, and 12 months in patients with NSAA. For patients with SAA and VSAA, these response rates were 46.7%, 61.5%, and 87.5%. Hepatotoxicity occurred in one patient. Fifty‐three blood samples were used to build the PPK model. Body weight was the only covariate for apparent clearance (CL/F) and volume of distribution. The allele‐T carrier of adenosine triphosphate‐binding cassette transporter G2 was found to increase eltrombopag's clearance. However, when normalized by weight, the clearance between the wild‐type and variant showed no statistical difference. In patients with response, children with NSAA exhibited lower area under the curve from time zero to infinity, higher CL/F, and higher weight‐adjusted CL/F than those with SAA or VSAA. However, the differences were not statistically significant. The results may support further individualized treatment of eltrombopag in children with AA.

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Efficacy and safety of eltrombopag in the first-line therapy of severe aplastic anemia in children

Cited by 14 publications

References 26 publications

Estimative of costs of two therapeutic schemes for aplastic anemia among young individuals

Estimative of costs of two therapeutic schemes for aplastic anemia among young individuals

Efficacy of eltrombopag with immunosuppressive therapy for children with acquired aplastic anemia

Efficacy, Safety, and Population Pharmacokinetics of Eltrombopag in Children with Different Severities of Aplastic Anemia

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