OBJECTIVE:

This study assesses the cost-effectiveness of eltrombopag in the treatment of hepatitis C virus (HCV)-related thrombocytopenia.

METHODS:

A Markov model was constructed on the basis of the clinical trials ENABLE 1 and ENABLE 2. Three alternatives were considered: scenario 1; treatment with eltrombopag in both the enabling phase and during antiviral therapy, as in the ENABLE trial design; scenario 2; no eltrombopag treatment and no antiviral therapy; scenario 3; no eltrombopag treatment and subsequent administration of a reduced dose of peg-IFN.

RESULTS:

Base case results demonstrate that scenario 1 is associated with a cost per QALY of €30,020.94 in comparison with scenario 2. The incremental cost-effectiveness ratio reaches a value of €32,752.44 per QALY when scenario 1 is compared with scenario 3.

CONCLUSION:

The use of eltrombopag in HCV patients with thrombocytopenia is cost-effective as it leads to a reduction in disease progression and thus a drop in the number of patients with advanced liver disease.

Background Eltrombopag is a thrombopoietin mimetic indicated in immune thrombocytopenia when corticosteroids or splenectomy are not effective or splenectomy is contraindicated. No direct comparison exists with romiplostim. Purpose To evaluate the effectiveness and safety of eltrombopag since its inclusion in the pharmacotherapeutic guide. Materials and methods Retrospective study of patients treated August 2011 - February 2013. Demographic data, pretreatments, splenectomy, platelet count (PC) at the beginning, at five weeks and at the end of the treatment or study, adverse effects and discontinuation, were collected. Results 8 women and 1 man, median age 63 (24-78). Five were splenectomised, all of them pretreated with corticosteroids, 7 with azathioprine, Danatrol or dapsone and 7 with romiplostim. Before treatment with romiplostim median PC was 4,000/mm3 (3,000-25,000) and after five weeks 75% had ≥50,000. 3 patients discontinued for inefficacy, 1 for partial response with a high dose, 2 for adverse effects and one was changed to eltrombopag for oral route administration. At the start of eltrombopag administration the median PC was 6,000 (2,000-68,000), after five weeks 44% had ≥50,000. At the end of study 6 patients had discontinued treatment, two due to lack of response, one was intolerant, one refused treatment for his liver disease, one was splenectomised and another had a sustained response. 3 patients continued with eltrombopag for a median of 70 weeks (57-78) and at the end of the study median platelet count was 45,000 (34,000-60,000). Thromboembolic complications, cataracts, bone marrow reticulin or liver damage were not reported. Two patients reported irritability and fatigue and another headache. Conclusions Both romiplostim and eltrombopag increased platelet count ≥50,000/mm3 more than placebo. Advantages of eltrombopag are oral versus subcutaneous administration and easier dosing. In an indirect comparison romiplostim achieved a better platelet response after 4 weeks of treatment, like in our study, but we observed more discontinuation with romiplostim due to lack of response or partial response (57% vs. 22%).

Study rationale is based on the data that in previous clinical studies of eltrombopag in ITP there are some patients who have been reported as non responders at the maximal approved dose of 75 mg daily. The trend in both normal volunteers and in patients with ITP suggest and increasing response rate with increased doses of eltrombopag up to a dose of 75mg. Previously published data has shown no overt increase in toxicity in normal volunteers, oncology patients and aplastic anemia patients treated with escalated doses as high or higher than those proposed in this study.

It therefore seems possible that in ITP patients who did not respond to a dose of 75mg daily, eltrombopag could be more effective at a higher dose. We propose a double blind randomized controlled trial in ITP patients who have been defined as non-responders at the maximum dose (75mg) of eltrombopag, assessing efficacy and toxicity at higher daily doses (100mg, 125 mg, 150 mg)

Eltrombopag is currently the only US Food and Drug Administration-approved thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia (ITP) in children. This oral, once-per-day therapy has shown favorable efficacy and adverse effect profiles in children. Two multicenter, double-blind, placebo controlled clinical trials (PETIT [Efficacy and Safety Study of Eltrombopag in Pediatric Patients With Thrombocytopenia From Chronic Idiopathic Thrombocytopenic Purpura (ITP)] and PETIT2 [Study of a New Medication for Childhood Chronic Immune Thrombocytopenia (ITP), a Blood Disorder of Low Platelet Counts That Can Lead to Bruising Easily, Bleeding Gums, and/or Bleeding Inside the Body]) demonstrated efficacy in raising platelet counts, reducing bleeding, and reducing the need for concomitant ITP therapies with relatively few adverse effects. The most commonly reported drug-related adverse effects include headache, nausea, and hepatobiliary laboratory abnormalities. Long-term safety data in children are limited, and studies in adults have not revealed a clinically significant increased incidence of thrombosis, marrow fibrosis, or cataract formation. Eltrombopag has also been approved for treating refractory severe aplastic anemia (AA) and has potential for expanded use in ITP and severe AA as well as in other conditions associated with thrombocytopenia.

Treatment of patients with chronic myelomonocytic leukemia (CMML) and thrombocytopenia.

Currently, sorafenib is the only available chemotherapeutic agent for advanced hepatocellular carcinoma (HCC), but it cannot be used in patients with liver cirrhosis (LC) or thrombocytopenia. In these cases, sorafenib is likely effective if given in combination with treatments that increase the number of platelets, such as thrombopoietin (TPO) receptor agonists. Increasing the platelet count via TPO treatment resulted in reduction of LC. Eltrombopag (EP), a TPO receptor agonist, has been reported to have antitumor effects against certain cancers, despite their lack of TPO receptor expression. We hypothesized that EP may possess antitumor activity against HCC in addition to its ability to suppress hepatic fibrosis by increasing the platelet count. In the present study, the antitumor activity of EP was examined by assessing the inhibition of cell proliferation and then ascertaining the ability of iron supplementation to reverse these effects in HepG2, Hep3B and Huh7 cells. In addition, a cell cycle assay was performed using flow cytometry, and signal transduction was evaluated by analyzing cell cycle-related protein expression. The results of EP were compared with those of the most common iron chelator, deferoxamine (DFO). The combined effect of EP and sorafenib was also assessed. The results revealed that EP exerts antitumor activity in HCC that is mediated by the modulation of intracellular iron content. EP suppressed the expression of the cell cycle-related protein cyclin D1 and elicited cell cycle arrest in the G0/G1 phase. The activity of EP was comparable to that of DFO in HCC, and EP did not compete with sorafenib at low concentrations. In conclusion, our findings suggest that EP is a good candidate chemotherapeutic agent for the treatment of HCC in patients with LC and thrombocytopenia.

An open-label, dose-adjustment, extension study to evaluate the safety and efficacy of eltrombopag for the treatment of subjects with idiopathic thrombocytopenic purpura (ITP) who have previously been enrolled in an eltrombopag trial. This study will allow adjustment of the eltrombopag dose to achieve an individualized dose and schedule for each subject. In addition, the ability to reduce the dose of concomitant ITP medications in the presence of eltrombopag, while maintaining platelet counts = 50,000/μL will be investigated.

This phase II trial is studying the effects of the drug eltrombopag has on thrombocytopenia (low platelet count). Eltrombopag is approved by the FDA for the treatment of thrombocytopenia (low platelet count) in adults who have had an insufficient response to medications such as corticosteroids and immunoglobulins. Eltrombopag is not approved by the FDA (Food and Drug Administration) for the treatment of thrombocytopenia refractory to platelet transfusion and so for this study is considered investigational.

An indirect comparison to compare the efficacy of eltrombopag versus romiplostim

BACKGROUND:

Immunosuppressive therapy with horse antithymocyte globulin and cyclosporine currently remains the standard therapy for children with severe aplastic anemia (SAA) who lack human leukocyte antigen (HLA)-identical sibling. The thrombopoietin receptor agonist eltrombopag has been recently approved for SAA patients 2 years and older. However, there are limited data on its safety and efficacy in pediatric cohorts.

METHODS:

We conducted a retrospective study of patients ≤18 years old consecutively diagnosed with SAA between 2000 and 2018. Patients received either standard immunosuppressive therapy (IST-Std) or IST with eltrombopag (IST-Epag). The primary outcome was the objective response (OR), including partial and complete response (CR), at 6 and 12 months after starting therapy.

RESULTS:

We identified 16 patients receiving IST-Std and nine IST-Epag treatment (seven of nine as upfront therapy and two of seven after previously failed IST). The OR at 6 and 12 months in IST-Std arm was 71% and 100%, with CR in 29% and 58%, respectively. Seven patients receiving upfront IST-Epag had OR at 6 and 12 months, with two of seven (29%) achieving CR at 6 and 12 months. Two patients who previously failed standard IST did not respond to eltrombopag. No significant differences were observed in both cohorts with regard to infections. One IST-Epag-treated patient developed transient grade 3 transaminitis. Finally, no changes in paroxysmal nocturnal hemoglobinuria (PNH) clone size and cytogenetic abnormalities were seen in either cohort.

CONCLUSION:

The addition of eltrombopag to standard IST was well tolerated and resulted in satisfactory hematological response at 6 and 12 months in this single-institution experience. A larger cohort with longer follow-up is required to assess response durability.