The goal of this clinical research study is to learn if eltrombopag given in combination with decitabine can help to control advanced MDS. The safety of this study drug combination will also be studied.

The purpose of this randomized, blinded, placebo-controlled study was to provide clinical safety and exploratory efficacy data on the use of Eltrombopag in adult subjects with Acute Myeloid Leukemia (AML) receiving standard induction chemotherapy with daunorubicin plus cytarabine. A minimum of 120 evaluable subjects newly diagnosed with AML was stratified by antecedent malignant hematologic disorder and age.

A long term observational ocular safety study in adults who have received study medication (either active drug or placebo) in a phase II or III clinical study evaluating eltrombopag. The study will follow subjects for 2.5 years following their last ocular assessment on their prior treatment study (regardless of the therapeutic indication) and will describe long-term ocular safety with respect to changes in the lenses over time from all subjects.

Aplastic anemia is a rare disorder characterized by pancytopenia and a hypo cellular bone marrow.but,It is very serious disease causing morbidity and mortality.

Aplastic anemia can be treated effectively with haematopoietic stem cell transplantation and immunosuppressive drug regimens but haematopoietic stem cell transplantation has limitations due to its cost and many patient are unsuitable. Immunosuppressive drug has a significant number of patients have persistent cytopenias. Currently, the treatment of these patients is regular transfusion, which are expensive, inconvenient, and associated with serious side effects related to iron overload and transfusion.

Eltrombopag is an oral thrombopoietin mimetic that selectively binds at the transmembrane and juxtamembrane domains of the thrombopoietin receptor, at sites distinct from the binding site of thrombopoietin therefore it does not compete for binding with the native molecule. It promoting thrombopoiesis and release of platelets from mature megakaryocytes. Also, promote other hematopoietic stem cell as well as in thrombopoiesis .

BACKGROUND:

Acquired aplastic anemia (AAA) in pediatric patients is a rare disorder characterized by hypocellular bone marrow and pancytopenia. Eltrombopag, an oral thrombopoietin receptor agonist, provides a hematologic improvement in adults with severe aplastic anemia (SAA) refractory to immunosuppressive therapy (IST). The association of ELT and IST was approved by the US Food and Drug Administration (FDA) for adults and children ≥2 years of age as a first-line treatment for SAA. However, the effects of ELT on pediatric patients with SAA remain controversial and limited.

METHODS AND FINDINGS:

We conducted a systematic review of the most recent literature from Pubmed, Web of Science, and Embase, published up to 20th December 2022, in order to evaluate the available evidence on the efficacy and safety of ELT added to IST for the treatment of SAA in the pediatric population.

CONCLUSION:

Eltrombopag added to the IST has shown a good safety profile, without manifestations of excessive toxic effects, although not all the results obtained from our studies support the addition of ELT to the IST in the first-line treatment of children with SAA.

SYSTEMATIC REVIEW REGISTRATION:

https://www.crd.york.ac.uk/prospero/, identifier: CRD42022325859.

Background and Aim: Many studies indicated that eltrombopag and romiplostim could improve hematopoietic function in patients with myelodysplastic syndromes (MDS), but their toxicity and efficacy were not known. This meta-analysis aimed to investigate the safety and efficacy of eltrombopag and romiplostim in MDS. Methods: A full-scale search strategy was used to search relevant published studies in PubMed, Embase, Web of Science, ClinicalTrials.gov and the Cochrane Library until January 2020 using a random-effects model and the pooled risk ratio (RR) with 95% confidence interval as the effect indicator. Statistical analyses were performed using RevMan 5.3. Results: This meta-analysis included eight studies comprising 1047 patients. A lower RR of overall response rate (ORR) (RR: 0.65; 95% CI, 0.47–0.9) and grade ≥3 bleeding events (RR: 0.36; 95% CI, 0.36–0.92) were observed after romiplostim and eltrombopag treatment compared with placebo. The pooled RR for the ORR and grade ≥3 bleeding events were 0.58 (95% CI.: 0.41–0.83, P = 0.003) and 0.6 (95% CI.: 0.37–0.96, P = 0.03) in eltrombopag, respectively. A lower ORR in intermediate- or high-risk MDS (RR: 0.63; 95% CI.: 0.45–0.88, P = 0.006) was observed. No difference in mortality, serious adverse events, platelet transfusion, hematologic improvement, and AML transformation was observed. Conclusions: Thrombopoietin receptor agonists (TPO-RAs) romiplostim and eltrombopag were effective in reducing bleeding events, especially grade ≥3 bleeding events. However, it might reduce the ORR of MDS, especially in eltrombopag treatment group or high-risk MDS group. Due to the limited treatment of MDS and the poor response to the drug, this may be a selection method for MDS combined with fatal bleeding, although further research is needed to confirm the effectiveness of this approach.

Background: Dengue is the most widespread aedes mosquito borne viral disease which infects more than 50 million people every year. The clinical symptoms of dengue may vary from mild fever to life-threatening incidents. Eltrombopag, a non-peptide, oral TPO-R agonist, small molecular weight is quandaries with the transmembrane domain of a TPO receptor and persuades the Janus Kinase/Signal transducer and activator of transcription pathway, with a significant rise in platelet production.Material & Methods:This study was a cross-sectional observational study which was conducted at Tairunnesa Memorial Medical College and Hospital (TMMCH), Gazipur and Shin Shin Japan Hospital, Uttara, Dhaka. The study was conducted in between July 2021- December 2021. The sample size for this study was 100.Results:The mean age in group 1 was 25� in group 2 29�and in control group 29� The mean Baseline PLT * 109 /L for group 1 was 57�, for group 2, 51� and for control group 54�. Mean of systolic baseline BP (mmHg) for group 1 was 103.55� 5.04 for group 2 was 105.38�.34 and for control group was 101.97�28 and followed by the mean of diastolic baseline BP (mmHg) was 72.83�56, 72.84�.93 and 71.97�75. AEs was found in 4(12.1%) cases of group 1 where in group 2 it was 2(5.9%) and in control group was 3(9.1%). In day 7, the recovery rate of group 1 was 93.9% and in group 2 the recovery rate was 94.1%.Conclusions:Dengue is a vector-borne viral disease which needs medical assistance because it may lead to life-threatening outcome. Eltrombopag can be considered as a therapeutic option to increase the PLT counts in DF and DHF patients in the management of thrombocytopenia.

Background: Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. Eltrombopag is a preferred second‐line treatment of ITP, but many patients still have no response or relapse due to unknown reasons. Our preclinical data indicate that rhein, the active metabolite of diacerein, can enhance megakaryocyte sensitivity to thrombopoietin receptor agonists, and promote megakaryocyte polyploidization and platelet formation in ITP. Thus, a prospective randomized controlled trial was conducted to compare the efficacy and safety of eltrombopag plus diacerein versus eltrombopag alone in adult ITP. Here we report the interim analysis of this study. Methods: This multicenter, open‐label, randomized, phase 2 trial screened eltrombopag‐inefficient or relapsed ITP patients from five tertiary medical hospitals in China. Eligible participants were randomly assigned into the combination arm (eltrombopag orally at an initial dose of 75 mg daily for 14 days, plus diacerein orally at an initial dose of 50 mg bid for 14 days) or the monotherapy arm (eltrombopag orally at an initial dose of 75 mg daily for 14 days) by masked statisticians. To maintain participants’ platelet counts at a safe range, individualized dosages were allowed to be adjusted by physicians according to the protocol. The primary outcome was initial response at day 15. Complete response was defined as a platelet count at or above 100×109/L and an absence of bleeding. Partial response was defined as a platelet count at or above 30×109/L but less than 100×109/L and at least a doubling of the baseline platelet count and an absence of bleeding. No response was defined as a platelet count of less than 30×109 cells per L, or less than two‐times increase from baseline platelet count, or bleeding. Key secondary enpoints included response at day 28, time to response (TTR), duration of response, bleeding scores, health‐related quality of life assessment and adverse events (AEs). This trial was registered with ClinicalTrials.gov (NCT04917679). Results: From September 2020 to December 2021, 90 patients were screened for eligibility, of whom 24 were ineligible, 66 were randomly assigned to receive either eltrombopag plus diacerein (n=32) or eltrombopag alone (n=34). Four patients did not receive allocated intervention and they were excluded from the analysis. Baseline characteristics were balanced between the two arms. The total population (female accounted for 51.6%) had a mean age of 42.6 years and a mean platelet count of 8.6 ×109/L. At day 15, a significantly higher proportion of participants in the eltrombopag plus diacerein arm (13 [43.3%] of 30) than in the eltrombopag monotherapy arm (5 [15.6%] of 32) had an initial response (p=0.0247). At day 28, the response rate in the combination arm was higher than that in the eltrombopag arm even though it did not reach statistical significance (10 [33.3%] of 30 vs 4 [12.5%] of 32, p=0.0699). There was no significant difference in median TTR between the two arms (p>0.05). During the follow‐up period, the duration of response was longer in the eltrombopag plus diacerein arm than in the eltrombopag arm by the Kaplan Meier analysis (Hazard ratio 0.57, 95% CI 0.34‐0.96, p=0.0178). Eltrombopag plus diacerein exhibited lower bleeding scores and better health‐related quality of life scores than eltrombopag. Incidence of AEs was similar between the two arms. Most of AEs were mild and resolved spontaneously after treatment was completed. The incidence of gastrointestinal reactions in the combination arm was slightly higher, but no significant difference was observed. There were no grade 4 or 5 AEs. No treatment‐related deaths occurred. Conclusions: In conclusion, our findings suggest that the addition of diacerein as a sensitizer to eltrombopag has improved initial response than eltrombopag alone for eltrombopag‐inefficient or relapsed ITP patients. This oral combination therapy warrants further exploration. [Formula presented] Disclosures: No relevant conflicts of interest to declare. OffLabel Disclosure:: It includes information or discussion of off‐label drug use of diacerein.

PURPOSE:

Eltrombopag is indicated in patients with severe aplastic anemia (SAA) refractory to prior immunosuppressive therapy. The combination of eltrombopag and immunosuppressive therapy (such as cyclosporine) is currently being evaluated in patients with treatment-naive SAA. Cyclosporine is a human breast cancer resistance protein (BCRP) inhibitor, and can potentially alter plasma exposure to eltrombopag, a BCRP substrate. This phase 1, open-label, randomized, 3-period, crossover study evaluated the effect of cyclosporine on the pharmacokinetics of eltrombopag in healthy adults.

METHODS:

Thirty-nine subjects were randomized to either single dose of eltrombopag 50 mg, cyclosporine 200 mg + eltrombopag 50 mg or cyclosporine 600 mg + eltrombopag 50 mg treatment groups. Eltrombopag pharmacokinetic parameters (Cmax, tmax, AUClast, AUCinf, %AUCex, t1/2, and CL/F) were determined using noncompartmental methods.

RESULTS:

Geometric mean AUCinf, AUClast, and Cmax, were decreased by 18, 20, and 25%, respectively, for cyclosporine 200 mg + eltrombopag and by 24, 22, and 39%, respectively, for cyclosporine 600 mg + eltrombopag groups compared to the eltrombopag alone group. The median tmax was prolonged by ~ 1 h in both coadministration treatments. The geometric mean t1/2 was ≈ 21, ≈ 24, and ≈ 26 h, respectively, in cyclosporine 200 mg + eltrombopag, cyclosporine 600 mg + eltrombopag and eltrombopag alone groups. All the treatments were safe and well-tolerated. No serious adverse event or death was reported during the study.

CONCLUSION:

These changes in exposure were not considered clinically meaningful as the dose of eltrombopag is adjusted using within-patient dose titration based on platelet counts.

BACKGROUND:

Eltrombopag is a new, orally active thrombopoietin-receptor agonist that stimulates thrombopoiesis. We evaluated its ability to increase platelet counts and facilitate treatment for hepatitis C virus (HCV) infection in patients with thrombocytopenia associated with HCV-related cirrhosis.

METHODS:

Seventy-four patients with HCV-related cirrhosis and platelet counts of 20,000 to less than 70,000 per cubic millimeter were randomly assigned to receive eltrombopag (30, 50, or 75 mg daily) or placebo daily for 4 weeks. The primary end point was a platelet count of 100,000 per cubic millimeter or more at week 4. Peginterferon and ribavirin could then be initiated, with continuation of eltrombopag or placebo for 12 additional weeks.

RESULTS:

At week 4, platelet counts were increased to 100,000 per cubic millimeter or more in a dose-dependent manner among patients for whom these data were available: in 0 of the 17 patients receiving placebo, in 9 of 12 (75%) receiving 30 mg of eltrombopag, in 15 of 19 (79%) receiving 50 mg of eltrombopag, and in 20 of 21 (95%) receiving 75 mg of eltrombopag (P<0.001). Antiviral therapy was initiated in 49 patients (in 4 of 18 patients receiving placebo, 10 of 14 receiving 30 mg of eltrombopag, 14 of 19 receiving 50 mg of eltrombopag, and 21 of 23 receiving 75 mg of eltrombopag) while the administration of eltrombopag or placebo was continued. Twelve weeks of antiviral therapy, with concurrent receipt of eltrombopag or placebo, were completed by 36%, 53%, and 65% of patients receiving 30 mg, 50 mg, and 75 mg of eltrombopag, respectively, and by 6% of patients in the placebo group. The most common adverse event during the initial 4 weeks was headache; thereafter, the adverse events were those expected with interferon-based therapy.

CONCLUSIONS:

Eltrombopag therapy increases platelet counts in patients with thrombocytopenia due to HCV-related cirrhosis, thereby permitting the initiation of antiviral therapy. (ClinicalTrials.gov number, NCT00110799.)