The investigators hypothesis is that eltrombopag given to patients with moderate to very severe aplastic anemia will result in an increase in platelet counts. The investigators hypothesize that in patients with moderate to very severe aplastic anemia, treatment with eltrombopag will lead to fewer platelet transfusions, red blood cell transfusions, and fewer bleeding events. The investigators hypothesize that in patients with moderate to very severe aplastic anemia, eltrombopag will have an acceptable toxicity rate \<3%, at doses that result in increased platelet counts. Finally the investigators hypothesize that plasma eltrombopag levels in peripheral blood will correlate with improved platelet counts.

OBJECTIVE:

This article conducts a systematic review of eltrombopag combined with immunosuppressive therapy for the treatment of aplastic anemia (AA), to demonstrate the effectiveness and safety of eltrombopag.

METHODS:

PubMed, Cochrane Library, Embase, OVID, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched. Studies that met the inclusion criteria were collected, ranging from the establishment of the database to August 2023. Two reviewers performed meta-analyses using the Cochrane systematic review method and RevMan 5.3 software.

RESULTS:

This meta-analysis enrolled 5 studies with a total of 542 AA patients, including 274 in the experimental group and 268 in the control group. Meta-analyses were performed for efficacy and adverse reactions. The endpoint of effects included 6-month complete response (CR), 6-month partial response (PR), and 6-month overall response (OR). Eltrombopag combined with immunotherapy showed significant improvements in 6-month CR (OR: 2.20; 95% CI;1.54-3.12; P < 0.0001) and 6-month OR (OR = 3.66, 95% CI 2.39-5.61, P < 0.001)compared to immunosuppressive therapy for AA patients. In terms of safety, eltrombopag combined with immunosuppressive therapy showed significantly increased pigment deposition and abnormal liver function compared to immunosuppressive therapy alone.

CONCLUSION:

Compared to immunosuppressive therapy alone, eltrombopag combined with immunosuppressive therapy showed significant improvements in 6-month CR and 6-month OR. However, it also resulted in increased pigment deposition and abnormal liver function in terms of safety.

Eltrombopag is clinically approved for use in immune thrombocytopenia (ITP), chronic hepatitis C-related thrombocytopenia, and aplastic anemia and suitable for children; however, data on its overall safety profile are scarce. This study aimed to explore the clinical features of adverse drug events (ADEs) associated with eltrombopag in different age groups using ICSRs from the World Health Organization database VigiBase and the US Food and Drug Administration Adverse Event Reporting System database from 2008 to 2022 in combination with a meta-analysis of data from randomized clinical trials in the literature from inception to July 28, 2022. We conducted disproportionality analyses by grouping patients into the following age groups: 0-17 (0-23 months，2-11 years, 12-17 years), 18-64, and ≥65 years. The ADEs about hepatobiliary disorders, thrombosis, skin and subcutaneous tissue disorders, infections and so on were observed more differently in each age group. Meta-analysis results showed differences in the four system organ classes between adults and children with

ITP:

infections and infestations, general disorders and administration site conditions, skin and subcutaneous tissue disorders, and investigations. The adverse drug reactions in the latest version of instructions were searched in the databases to analyze their post-marketing safety signal strength. We observed signals of elevated alanine aminotransferase, aspartate aminotransferase, and blood bilirubin levels in all age groups. For children, urinary tract infection and back pain, showed signals. Due to the inherent limitations of pharmacovigilance studies, more experiments are needed to assess the risks of eltrombopag in different ages.

BACKGROUND:

The immune-mediated destruction of hematopoietic stem cells is implicated in the pathophysiology of aplastic anemia (AA). Immunosuppressive therapy (IST) using antithymocyte globulin and cyclosporine is successful in this setting. Eltrombopag is active in patients with refractory AA, presumably by increasing the bone marrow progenitors.

METHODS:

This phase 2 trial initially was designed to evaluate standard IST in newly diagnosed patients with severe AA and later was amended to add eltrombopag to simultaneously address immune destruction and stem cell depletion. The primary outcome was the overall response rate (ORR) at 3 months and 6 months.

RESULTS:

A total of 38 patients were enrolled: 17 (45%) received IST alone and 21 (55%) received additional eltrombopag. The ORR was 74%. Patients receiving IST plus eltrombopag had a similar ORR (76% vs 71%; P = .72), complete remission rate (38% vs 29%; P = .73), and median time to response (84 days vs 57 days; P = .30) compared with those receiving IST alone. The 2-year overall survival rate in the IST group was 91% compared with 82% for those patients treated with IST plus eltrombopag (P = .82). No cumulative toxicities were noted after the addition of eltrombopag.

CONCLUSIONS:

The addition of eltrombopag to standard IST was well tolerated and resulted in similar responses.

AIM:

Eltrombopag is a highly effective treatment for immune thrombocytopenia (ITP). Cases of durable remission after the discontinuation of eltrombopag in adult ITP have recently been reported; however, the frequency and mechanisms responsible for this phenomenon remain unknown. In the present study, we examined the phenotypes of lymphocytes in ITP to clarify whether they predict outcomes after the discontinuation of eltrombopag.

METHODS:

We analysed 56 adult ITP patients treated with eltrombopag at our hospital between January 2008 and January 2020. Patients' characteristics at the initiation and discontinuation of eltrombopag, the prognostic significance of lymphocytes and other factors were evaluated.

RESULTS:

A total of 38 patients showed complete response (CR). Eltrombopag was discontinued in 28 of 38 patients who achieved CR. Among the 28 patients, 12 (42.8%) had an immediate relapse after discontinuing eltrombopag and 16 (57.2%) showed sustained response without additional ITP therapy, despite discontinuing eltrombopag, with a median follow-up of 42 months. No significant differences were observed in platelets, the median duration of eltrombopag, the absolute number of T, B and NK cells at the initiation of eltrombopag between patients who sustained response and those who relapsed after discontinuing eltrombopag. However, the number of B and NK cells at the discontinuation of eltrombopag was higher in patients who sustained response than in those who relapsed (P = .022 and P = .012 respectively).

CONCLUSIONS:

The present results indicate that the absolute number of B (≥0.20 × 10[9] /L) and NK (≥0.30 × 10[9] /L) cells at the discontinuation of eltrombopag contributes to the prediction of outcomes.

OBJECTIVE To provide a reference for the safe use of thrombopoietin receptor agonists romiplostim and eltrombopag in clinic. METHODS FDA adverse event reporting system （FAERS） in the United States was adopted to collect adverse drug event （ADE） reports of romiplostim and eltrombopag from their launch in the United States to September 30， 2022； the ADE signals of the two drugs were analyzed using the reporting odds ratio （ROR） method and the comprehensive standard method of the UK Medicines and Healthcare Products Regulatory Agency. RESULTS A total of 14 021 and 4 431 ADE reports were collected about romiplostim and eltrombopag， respectively， with a gender composition of more females than males. After signal screening， 563 ADE signals were obtained about romiplostim， involving 25 system organ classes （SOC）； eltrombopag had 433 ADE signals， involving 26 SOC. The most frequently reported ADE for both drugs was platelet count decreased （2 060， 1 585 cases）， which was mentioned in their drug instructions. In terms of signal intensity， romiplostim exhibited the highest signal for abnormal thrombopoietin levels （ROR of 2 268.85）， while eltrombopag had the highest signal for positive dengue virus test （ROR of 954.50）， with neither of these signals mentioned in their respective drug instructions. CONCLUSIONS The ADE of romiplostim and eltrombopag mainly affects the blood and lymphatic system， and there are many new suspicious high-risk signals.

Primary Objective: To assess safety of eltrombopag in pediatric patients undergoing intensive chemotherapy for malignant solid tumors.

Secondary Objectives: To assess the efficacy of eltrombopag in increasing platelet count up to 2 weeks after completion of chemotherapy in pediatric patients undergoing intensive chemotherapy for malignant solid tumors.

Hypothesis: The hypothesis is that eltrombopag an oral thrombopoietin receptor agonist will increase the platelet count safely and efficaciously in children having chemotherapy induced thrombocytopenia while on therapy for solid tumors.

Randomized, open-label, multicenter study to compare the efficacy and safety of zanubrutinib plus eltrombopag compared to eltrombopag monotherapy for the first-line treatment of adults with chronic immune thrombocytopenia (ITP).

BACKGROUND AND OBJECTIVES:

Eltrombopag is a thrombopoietic growth factor that is approved for the treatment of thrombocytopenia in chronic hepatitis C virus (HCV) patients. We aimed to describe eltrombopag population pharmacokinetics in hepatitis C patients. Bayesian statistical approach will be applied to screen for patients' characteristics associated with eltrombopag pharmacokinetic parameters.

METHODS:

A population pharmacokinetic analysis was conducted using WinBUGS version 1.4.3. Data from 483 individuals with chronic HCV infection were analyzed. This analysis is a secondary analysis of two clinical studies (ENABLE1 and ENABLE2) sponsored by GlaxoSmithKline. Several patients' characteristics were examined as possible covariates of the population pharmacokinetic model. Prior information from previous studies was incorporated in the bayesian model as prior distribution to estimate pharmacokinetic parameters.

RESULTS:

A two-compartment pharmacokinetic model with first-order absorption with exponential error model best fit the data. We identified East Asian race and total bilirubin level as predictors of eltrombopag clearance. Typical value for distributional clearance was 0.762 L/h (95% Bayesian credible set, 0.703-0.826), for volume of distribution of the central and peripheral compartments were 12 L (10.9-13.4) and 10.9 L (10.4-11.5), and for absorption lag time was 0.947 h (0.918-0.977). Assuming an average total bilirubin of 21.7 µmol/L, the typical elimination clearance value for an East Asian patient was 0.14 L/h and for other races was 0.20 L/h.

CONCLUSIONS:

Eltrombopag pharmacokinetic behavior was described using population bayesian approach. This model can be applied to optimize eltrombopag dosing in order to reduce the incidence of thrombocytopenia in HCV-infected patient receiving interferon-based therapy.

Immune thrombocytopenia (ITP) may occur in isolation (primary) or in association with a predisposing condition (secondary ITP [sITP]). Eltrombopag is a well-studied treatment for primary ITP, but evidence is scarce for sITP. We evaluated real-world use of eltrombopag for sITP using electronic health records. Eligible patients had diagnoses of ITP and a qualifying predisposing condition, and eltrombopag treatment. We described patient characteristics, treatment patterns, platelet counts, and thrombotic and bleeding events. We identified 242 eligible patients; the most common predisposing conditions were hepatitis C and systemic lupus erythematosus. Average duration of eltrombopag treatment was 6.1 months. Most (81.4%) patients achieved a platelet count ≥ 30,000/µL at a mean of 0.70 months, 70.2% reached ≥ 50,000/µL at a mean of 0.95 months, and 47.1% achieved a complete response of > 100,000/µL at a mean of 1.43 months after eltrombopag initiation. At eltrombopag discontinuation, 105 patients (43%) experienced a treatment-free period for a mean 3.3 months. Bleeding events occurred with similar frequency before and during eltrombopag treatment whereas thrombotic events were less frequent during eltrombopag treatment. Our results suggest similar rates of platelet response with eltrombopag in patients with sITP as compared with primary ITP. In addition, a treatment-free period is possible for a substantial minority of patients.