Eltrombopag in Combination with Rabbit Anti-thymocyte Globulin/Cyclosporine A in Immunosuppressive Therapy-naïve Patients with Aplastic Anemia in Japan

Imada, Kazunori; Obara, Naoshi; Iida, Hiroatsu; Imajo, Kento; Maeda, Takeyasu; Usuki, Kensuke; Zhang, Fanghong; Hombo, Yosuke; Tajima, Tsuyoshi; Kumagai, Akiko; Matsuda, Akihisa; Nakao, Shinji

doi:10.2169/internalmedicine.6063-20

Cited by 15 publications

(9 citation statements)

References 34 publications

(47 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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%

See 1 more Smart Citation

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

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.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

show abstract

“… 25 However, in a recent study of ELTR in combination with rabbit ATG/CsA in treatment-naïve patients with AA by Imada and colleagues, clinically significant clonal evolution or cytogenetic abnormalities were also not observed during a long follow-up. 29 De Latour and colleagues showed that the prevalence of somatic mutations was not higher in the ELTR group than in the IST group. 26 Therefore, the role of adding ELTR upfront in boosting clonal evolution is still unclear, and a much longer follow-up is needed to shed light on this issue.…”

Section: Discussionmentioning

confidence: 96%

Efficacy of combined immunosuppression with or without eltrombopag in children with newly diagnosed aplastic anemia

et al. 2023

View full text Add to dashboard Cite

We compared the efficacy and safety of eltrombopag (ELTR) combined with immunosuppressive therapy (IST) and IST alone in treatment-naïve children with severe (SAA) and very severe (vSAA) aplastic anemia. Ninety-eight pediatric patients were randomized to receive horse antithymocyte globulin and cyclosporin A with (n=49) or without (n=49) ELTR. The primary endpoint was the overall response rate (ORR) at 4 months. After 4 months, nonresponders were crossed over to the alternative group. In all patients, the ORR in ELTR+IST and IST groups was similar (65% vs. 53%, p=0.218); however, the complete response (CR) rate was significantly higher in ELTR+IST group (31% vs. 12%, p=0.027). In severity subgroups, the ORR was 89% vs. 57% (p=0.028) in favor of IST+ELTR in SAA, but it did not differ in patients with vSAA (52% vs. 50%, p=0.902). At 6 months after the crossover, 61% of initial ELTR(-) patients achieved a response compared to 17% of initial ELTR(+) patients (p=0.016). No significant difference in ELTR+IST and IST groups was observed in the 3-year OS (89% vs. 91%, p=0.673) or the 3-year EFS (53% vs. 41%, p=0.326). There was no unexpected toxicity related to ELTR. Adding ELTR to standard IST was well tolerated and increased the CR rate. The greatest benefit from ELTR combined with IST was observed in patients with SAA, but not in those with vSAA. The second course of IST resulted in a high ORR in initial ELTR(-) patients who added ELTR and had limited efficacy among patients who received ELTR upfront. Clinicaltrials.gov #NCT03413306.

show abstract

“…In the current study, erythrocyte response rate was much lower than that of granulocyte and megakaryocyte. Thus, for NSAA patients suffering from anemia, more aggressive treatment such as CsA combined with ATG, androgen or eltrombopag should be considered ( 24 , 25 ).…”

Section: Discussionmentioning

confidence: 99%

Cyclosporine Monotherapy in Pediatric Patients With Non-severe Aplastic Anemia: A Retrospective Analysis

Yang

et al. 2022

Front. Med.

View full text Add to dashboard Cite

ObjectiveThe management of children with non-severe aplastic anemia (NSAA) is undefined and the efficacies and benefits of immunosuppressive therapy remain inconsistent. The study aimed to investigate the efficacy of Cyclosporine (CsA) monotherapy for pediatric NSAA.MethodsClinical data of children with NSAA who had been treated with CsA monotherapy at the outpatient department of Beijing Children's Hospital, Capital Medical University, National Children's Medical Center from January 2017 to March 2021 was collected retrospectively. Patients who had been treated <1 years until the end of follow-up were excluded. Transfusion-independent NSAA was further divided into moderate NSAA and mild NSAA according to the degree of cytopenia. Progression was defined as the development of transfusion-dependent AA or SAA and relapse was considered when treatment failed after initial response.ResultsA total of 95 pediatric patients with NSAA were enrolled in this study with 49 (51.6%) patients confirmed as mild NSAA, 38 (40%) as moderate NSAA and 8 (8.4%) as transfusion-dependent NSAA. The median treatment time of CsA was 22 (12–44) months. The overall response rate (ORR) was 57.9%, with 30.5% CR and 27.4% PR. Unexpectedly, patients with mild NSAA acquired lowest ORR (46.9%), then patients with moderate NSAA (63.2%), while 8 patients who were transfusion-dependent all had an active response to CsA. The granulocyte and megakaryocyte response was 46.9 and 55.8% respectively, while the erythrocyte response rate was as low as 22.5%. Univariate analyses revealed that patients with lower platelet count and higher interleukin 10 level predict an active response to CsA while higher level of fetal hemoglobin (HbF) tended to be a negative factor. Data of Treg cells before and after 1 year's treatment was available in a total number of 40 patients. Paired comparison found that the percentage of Treg cells in CD4+ T cells was decreased after 1 year's treatment of CsA (6.78 ± 2.72 vs. 5.23 ± 2.06, P = 0.001),both in responders and non-responders. The degree of decline in Treg cells between two distinctive response groups had no significant difference (P>0.05). With a median follow-up time of 22 months, 10.9% of responders relapsed and maintained NSAA while 27.5% of non-responders progressed to SAA or became transfusion-dependent. The overall progression rate was 11.6%.ConclusionCsA monotherapy had heterogeneous effects in the treatment of children NSAA Treatment approaches should be hierarchical and individual in clinical. Patients with lower platelet count and higher interleukin 10 level predicted an active response to CsA. While higher level of fetal hemoglobin (HbF) tended to be a negative factor. The percentage of Treg cells in CD4+ T cells was decreased broadly after treatment.

show abstract

Eltrombopag in Combination with Rabbit Anti-thymocyte Globulin/Cyclosporine A in Immunosuppressive Therapy-naïve Patients with Aplastic Anemia in Japan

Cited by 15 publications

References 34 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 combined immunosuppression with or without eltrombopag in children with newly diagnosed aplastic anemia

Cyclosporine Monotherapy in Pediatric Patients With Non-severe Aplastic Anemia: A Retrospective Analysis

Contact Info

Product

Resources

About