Outcomes of Eltrombopag Treatment and Development of Iron Deficiency in Children With Immune Thrombocytopenia in Turkey

Yozgat, Ayça Koca; Leblebisatan, Göksel; Akbayram, Sinan; Özel, Simge Çınar; Karakaş, Zeynep; Erduran, Erol; Yılmaz, Şebnem; Koçak, Ülker; Ünal, Şule; Özdemir, Nihal; Albayrak, Meryem; Zengin, Emine; Oymak, Yeşim; Bör, Özcan; Çakmaklı, Hasan Fatih; Söker, Murat; Gökçebay, Dilek Gürlek; Tokgöz, Hüseyin; Malbora, Barış; Karaman, Serap; Çelkan, Tiraje; Şaşmaz, İlgen; Yaralı, Neşe; Ören, Hale; Ünüvar, Ayşegül; Özbek, Namık

doi:10.4274/tjh.galenos.2020.2019.0380

Cited by 11 publications

(17 citation statements)

References 25 publications

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“…The most common side effects of eltrombopag treatment in children are elevated liver enzymes, headache, upper respiratory tract infection, and diarrhea. [ 15 , 16 ] No adverse reaction was observed in our patient.…”

Section: Discussionmentioning

confidence: 54%

Immune thrombocytopenia associated with Hashimoto thyroiditis in a pediatric patient

et al. 2021

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Rationale: Immune thrombocytopenia (ITP) is one of the most commonly acquired bleeding diseases in children. Infection and autoimmune disorders are the most common causes of ITP. The pathogenic mechanism of ITP is complex and is not completely understood. Understanding the underlying causes or disorders of ITP will improve the prognosis and make therapy more targeted. Patient concerns: An 8-year-old girl with ITP responded poorly to first- and second-line treatment. The patient showed multiple scattered petechiae, ecchymoses, and purpura in the skin and blood clots in the oral mucous membrane. Diagnoses: The patient was diagnosed with ITP associated with Hashimoto thyroiditis. Interventions: The patient was admitted to our emergency department and received platelet transfusion, IVIG, glucocorticoids and eltrombopag. The patient's thrombocytopenia resolved within 18 days after the administration of levothyroxine treatment. Outcomes: The patient was diagnosed with Hashimoto thyroiditis, and the platelet count recovered on the 3rd day of levothyroxine treatment. The platelet count became steadily normal with levothyroxine and prednisone treatment within 2 months of follow-up. Lessons: Early identification of the underlying reasons and treatment with multiple modalities may be useful in improving the prognosis of ITP. The treatment of thyroid disease and restoration of the euthyroid state impact the clinical outcome of ITP in children.

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Section: Discussionmentioning

confidence: 54%

Immune thrombocytopenia associated with Hashimoto thyroiditis in a pediatric patient

et al. 2021

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“…However, because safety is paramount, we have chosen to be particularly conservative with exclusion criteria, and we have chosen stringent cut-offs of transaminases and bilirubin. Iron deficiency has been reported in two retrospective series of patients treated with eltrombopag, 9 27 and we will be able to follow this larger cohort of patients prospectively to better evaluate the incidence of this potential side effect.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, we will investigate changes in iron indices (serum iron, total iron binding capacity (TIBC), transferrin saturation, ferritin, mean corpuscular volume (MCV) and haemoglobin) given the chelation properties of eltrombopag. 9 27 Secondary analyses will also include comparison of patient-related outcomes for patients treated with eltrombopag versus those treated with standard first-line agents. This includes comparison of significant bleeding (WHO Bleeding Scale ≥2 28 or Modified Buchanan Score ≥3 24 ), change in HRQoL measured by the Kids ITP Tool, 29 and fatigue as measured by the parent-proxy report of the Hockenberry Fatigue Scale-Parent.…”

Section: Methods and Analysismentioning

confidence: 99%

“…The primary objective of the trial is to determine if the proportion of patients with a platelet response is significantly greater in patients with newly diagnosed ITP treated with eltrombopag than those treated with standard first-line pharmacological treatment. The primary endpoint, platelet response, is defined as ≥3 of 4 non-consecutive weeks with platelets >50×10 9 /L during weeks 6-12 of therapy. We hypothesise that children with newly diagnosed ITP treated with eltrombopag will have an increased likelihood of a sustained platelet response as compared with those treated with standard therapy.…”

Section: Methods and Analysis Study Objectives And Hypothesismentioning

confidence: 99%

“…The majority of the literature to date evaluating the use of eltrombopag in the paediatric population has been in the setting of chronic ITP ( table 2 ), although multicentre retrospective studies document that paediatric haematologists are using TPO-RAs off-label in some cases of newly diagnosed ITP. 9 10 Eltrombopag has been studied prospectively for adults with newly diagnosed ITP in two small single-centre trials. A single-arm study of dexamethasone in combination with 4 weeks of eltrombopag used upfront in adult patients with newly diagnosed ITP produced 100% response (platelets >30×10 9 /L) at completion of therapy, and 66.7% relapse-free survival at 1 year, better outcomes than expected for comparable patients treated with steroids alone.…”

Section: Introductionmentioning

confidence: 99%

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Phase 3 randomised trial of eltrombopag versus standard first-line pharmacological management for newly diagnosed immune thrombocytopaenia (ITP) in children: study protocol

et al. 2021

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IntroductionImmune thrombocytopaenia (ITP) is an acquired disorder of low platelets and risk of bleeding. Although many children can be observed until spontaneous remission, others require treatment due to bleeding or impact on health-related quality of life. Standard first-line therapies for those who need intervention include corticosteroids, intravenous immunoglobulin and anti-D globulin, though response to these agents may be only transient. Eltrombopag is an oral thrombopoietin receptor agonist approved for children with chronic ITP who have had an insufficient response to corticosteroids, intravenous immunoglobulin or splenectomy. This protocol paper describes an ongoing open-label, randomised trial comparing eltrombopag to standard first-line management in children with newly diagnosed ITP.Methods and analysisRandomised treatment assignment is 2:1 for eltrombopag versus standard first-line management and is stratified by age and by prior treatment. The primary endpoint of the study is platelet response, defined as ≥3 of 4 weeks with platelets >50×109/L during weeks 6–12 of therapy. Secondary outcomes include number of rescue therapies needed during the first 12 weeks, proportion of patients who do not need ongoing treatment at 12 weeks and 6 months, proportion of patients with a treatment response at 1 year, and number of second-line therapies used in weeks 13–52, as well as changes in regulatory T cells, iron studies, bleeding, health-related quality of life and fatigue. A planned sample size of up to 162 randomised paediatric patients will be enrolled over 2 years at 20 sites.Ethics and disseminationThe study has been approved by the centralised Baylor University Institutional Review Board. The results are expected to be published in 2023.Trial registration numberNCT03939637.

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Long‐term eltrombopag for bone marrow failure depletes iron

et al. 2022

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Eltrombopag (EPAG) has been approved for the treatment of aplastic anemia and for immune thrombocytopenia, and a subset of patients require long-term therapy. Due to polyvalent cation chelation, prolonged therapy leads to previously underappreciated iron depletion. We conducted a retrospective review of patients treated at the NIH for aplastic anemia, myelodysplastic syndrome, and unilineage cytopenias, comparing those treated with EPAG to a historical cohort treated with immunosuppression without EPAG. We examined iron parameters, duration of therapy, response assessment, relapse rates, and common demographic parameters. We included 521 subjects treated with (n = 315) or without EPAG (n = 206) across 11 studies with multiyear follow-up (3.6 vs. 8.5 years, respectively). Duration of EPAG exposure correlated with ferritin reduction (p = 4 Â 10 À14 ) regardless of response, maximum dose, or degree of initial iron overload. Clearance followed first-order kinetics with faster clearance (half-life 15.3 months) compared with historical responders (47.5 months, p = 8 Â 10 À10 ). Risk of iron depletion was dependent upon baseline ferritin and duration of therapy. Baseline ferritin did not correlate with response of marrow failure to EPAG or to relapse risk, and timing of iron clearance did not correlate with disease response. In conclusion, EPAG efficiently chelates total body iron comparable to clinically available chelators. Prolonged use can deplete iron and ultimately lead to iron-deficiency anemia mimicking relapse, responsive to iron supplementation. | INTRODUCTIONEltrombopag (EPAG) is a nonpeptide human thrombopoietin receptor (TPOR) agonist developed for treatment of thrombocytopenias, most notably chronic immune thrombocytopenia (ITP). 1,2 It has since proven to be active in the treatment of several forms of bone marrow failure, 3,4 with regulatory approvals for single-agent use in immunosuppressive therapy (IST)-refractory severe aplastic anemia (SAA) 5 and in combination with IST as first-line therapy for SAA. 6 However, despite excellent response rates in AA, ITP, and other conditions, patients often remain EPAG-dependent for many years. The consequences of such prolonged EPAG exposure are less defined, particularly at the 3-fold higher doses utilized for AA as compared with ITP.An unexpected property of EPAG is its ability to chelate polyvalent cations, 7 including iron. In vitro, EPAG binds iron with an affinity similar to that of chelators such as deferoxamine (DFO) or deferasirox (DFX). 8 EPAG has significantly greater intracellular uptake, allowing it to access the tissue-confined labile iron pool. Indeed, we and others have shown that tissue-resident iron is readily mobilized into the plasma pool during EPAG treatment, leading to increased serum iron levels and the curious phenomenon of gray-colored blood. 9

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Outcomes of Eltrombopag Treatment and Development of Iron Deficiency in Children With Immune Thrombocytopenia in Turkey

Cited by 11 publications

References 25 publications

Immune thrombocytopenia associated with Hashimoto thyroiditis in a pediatric patient

Immune thrombocytopenia associated with Hashimoto thyroiditis in a pediatric patient

Phase 3 randomised trial of eltrombopag versus standard first-line pharmacological management for newly diagnosed immune thrombocytopaenia (ITP) in children: study protocol

Long‐term eltrombopag for bone marrow failure depletes iron

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