Background: Eltrombopag is the first oral nonpeptide TPO-R agonist approved, as single agent for the treatment of chronic immune thrombocytopenia (ITP). However, information dealing with the concomitant use of eltrombopag and high-dose dexamethasone in patients with chronic ITP are limited. Aims: we assessed the efficacy and safety of eltrombopag in combination with high-dose dexamethasone in a consecutive, unselected cohort of chronic ITP patients treated at single institution in the period May 2014-March 2017. Methods: nineteen patients (11 F/8 M) with median age 53 years (range, 29-75) who had at least a 6-month history of ITP (median 26 months; range 6-220 months) were eligible for this retrospective evaluation. All patients had a platelet count lower than 30.000/μL and bleeding manifestations were present in 13 out of 19. No patient had an active infection, drug-associated thrombocytopenia, positive serology for HIV, hepatitis B or hepatitis C, malignant diseases or was pregnant. Eltrombopag treatment was initiated at 50mg once a day in all patients. Dose and schedule were individualized with the goal of achieving and maintaining platelets ≥50.000/μL, eltrombopag dose did not exceed 75mg/day. Dexamethasone 40mg/day was given for 4 days every 28 days. Patients with glucose intolerance or diabetes who needed therapy received mitigated dose of dexamethasone (20mg/day). Response and complete response (CR) required an increase of platelet count above 50.000/μL and 130.000/μL, respectively. Results: all patients achieved a response during the treatment while a CR was obtained in 16 of 19 patients. Maximum response was reached after a median time of 9 weeks (range, 2-39). After a median follow-up time of 66 weeks (range, 9-149) response was still maintained in all patients while five patients lost CR. Four patients who lost CR were receiving maintainence therapy with eltrombopag (50/75mg/day from a period ranging between 2 and 14 weeks). In the fifth patient CR was lost 7 weeks after treatment was interrupted because of pregnancy. Conclusions: results of this study although limited by the small sample size and the lack of a comparative randomized design suggest that high-dose dexamethasone in combination with a thrombopoiesis stimulating agent led to a long-lasting remission of ITP. Highdose dexamethasone may modify the immunological milieu, resulting in an enhanced response to the thrombopoietin receptor agonist.

Chronic immune thrombocytopenic purpura (ITP) is characterized by low platelet counts and the risk of severe bleeding complications. The two recently introduced TPO-RA drugs, namely, eltrombopag and romiplostim, have shown efficacious sustained response with continuous administration. Both drugs are indicated for the treatment of thrombocytopia in patients with chronic ITP who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. While these trials address important clinical questions they were not intended to evaluate what happens in the real-world settings with actual patient living daily lives. The purpose of this health outcomes study is to understand how the two TPO receptor agonists (TPO-RA) currently available in the US are being used in clinical practice and how their use impacts chronic ITP patients\' daily lives. The study hypothesis is that patients who switched to eltrombopag report a better health-related quality of life than those who switched to romiplostim. This study utilized a hybrid design of retrospective chart review study and cross-sectional patient survey. A customized Patient Case Report Form (CRF) will be used to retrospectively collect clinical data from patient medical charts where the primary cohorts consist of patients who have switched from other ITP medication to eltrombopag or romiplostim. A cross-sectional survey will be employed to collect patient reported outcomes (PRO) data, including health-related quality of life and treatment satisfaction, using a compository questionnaire. Analyses of cross-sectional survey data and retrospective medical chart review data in patients who switch to either eltrombopag or romiplostim from their prior primary therapy will be conducted.

The purpose of this study was to evaluate the efficacy and safety of eltrombopag in combination with cyclosporine alone as first-line therapy on overall hematologic response

This is an open label, multi-centre, dose ranging study to assess efficacy, safety and pharmacokinetics of eltrombopag in thrombocytopenic subjects with chronic liver disease.

This study is designed to evaluate the efficacy and safety of eltrombopag monotherapy in Japanese adult patients with platelet transfusion-dependent lower-risk Myelodysplastic syndromes (LR-MDS).

This is a prospective, open-label, randomized, two-arm clinical trial conducted to evaluate the safety and efficacy of romiplostim in comparison with eltrombopag in the treatment of thrombocytopenia in patients with Wiskott-Aldrich syndrome

Background. Most therapies for chronic immune thrombocytopenia (cITP) have side effects that reduce their tolerability in children. PETIT is an ongoing open-label and randomized, placebo-controlled trial to investigate efficacy and safety of eltrombopag in children with cITP who failed initial therapy and have platelets <30,000/μL. Aims. To report open-label data from PETIT. Methods. Five patients were enrolled in Cohort 1 (12-17 years) and received open-label eltrombopag. After 12 weeks, safety, pharmacokinetics, and platelet counts were reviewed and 18 patients (not part of this abstract) were randomized 2:1 to eltrombopag or placebo. All patients received 24 weeks of eltrombopag therapy. In Cohort 1, the 12-week review identified no safety issues, so dosing began for 5 open-label patients in Cohort 2 (6-11 years), with identical procedures followed for safety review and randomization of 18 patients. Cohort 3 (1-5 years) opened once data from the completed randomized periods of Cohorts 1 and 2 were evaluated by an independent data safety monitoring board.Conservative starting doses were used (Cohort 1, 25 mg daily; Cohort 2, 25 mg [weight ≥27 kg] or 12.5 mg [<27 kg]; Cohort 3, 0.7 mg/kg) and adjusted as needed to a maximum of 75 mg daily, to maintain platelet count ≥50,000- <400,000/μL. Starting doses were reduced 50% for East Asian patients. Assessments were weekly until a stable dose was achieved and monthly thereafter. Response was platelets ≥50,000/μL at any time in the absence of rescue treatment. Results. Data from the 15 open-label patients, 5 from each cohort, are presented (Table 1). At baseline, 9 (60%) patients had platelets ≤15,000/μL, 1 was splenectomized, and 1 was receiving a stable dose of methylprednisolone.Median doses during 24 weeks were 75 mg for both Cohorts 1 and 2, and 70 mg for Cohort 3. All patients completed 24 weeks of treatment.Response was achieved at least once by 80% of patients (4/5 in each cohort). Between weeks 17-24, 8/15 (53%) patients had platelets ≥50,000/μL in ≥50% assessments and 11/15 (73%) had ≥30,000/μL in 80% of assessments, without rescue treatment. The patient receiving methylprednisolone discontinued it after 71 days. Seven (47%) patients received rescue treatment. Incidence of WHO bleeding grades 1-4 and 2-4 was 87% (13/15) and 33% (5/15) at baseline, decreasing to 50% (7/14) and 7% (1/14) by Week 24.All patients reported adverse events (AEs). 88% were grades 1-2, 9% were not graded, and there was 1 grade 4 AE (neutropenia). Serious AEs were reported for 2 patients (neutropenia, epistaxis). The most common AEs were headache (8 patients, 53%), vomiting (7, 47%) and diarrhea (5, 33%). No patient had AEs of liver enzyme elevation or thrombosis, and none were withdrawn due to AEs.Summary and Conclusions. Preliminary data suggest that eltrombopag is safe and potentially effective for children with cITP failing first-line therapy. No safety issues prevented enrollment into subsequent cohorts or the double-blind phase. Efficacy conclusions are limited by small patient numbers, lack of comparator arm, and low starting doses. The ongoing randomized study will further characterize safety and efficacy of eltrombopag in childhood cITP. (Figure Presented).

INTERVENTION:

Trade Name: Revolade Product Name: Eltrombopag Pharmaceutical Form: Film‐coated tablet

CONDITION:

Inherited thrombocytopenias ; MedDRA version: 20.0 Level: HLT Classification code 10043555 Term: Thrombocytopenias System Organ Class: 100000004851 Therapeutic area: Diseases [C] ‐ Blood and lymphatic diseases [C15]

PRIMARY OUTCOME:

Main Objective: The primary objective of the study is to estimate the response to eltrombopag based on platelet count increase and lack of requirement for PC transfusion for performing invasive acts at mild or high bleeding risk Primary end point(s): Full response (“success”) is defined as an increase in platelet count above the safety level and a procedure performed without PC transfusion, Secondary Objective: The secondary objective is to document in this particular setting the safety profile of eltrombopag, the kinetics of platelet recovery and the predictive value Inherited thrombocytopenia (IT) type, serum thrombopoietin (TPO) level and baseline platelet count on the response to eltrombopag. Timepoint(s) of evaluation of this end point: 4 weeks

SECONDARY OUTCOME:

Secondary end point(s): Adverse effects recorded during treatment and the 4‐week follow‐up after discontinuation, including excessive bleeding or any complication related to bleeding or thrombotic events.; Serial platelet counts and change in platelet size; Timepoint(s) of evaluation of this end point: 1/week during 8 weeks

INCLUSION CRITERIA:

Related to patients: Symptomatic inherited thrombocytopenia (IT) with family history and/or molecular identification with an average platelet count in the previous year below the safety level required for the procedure. Written informed consent of the patient or relatives. Related to the procedure: scheduled (=4 weeks) invasive procedure with anticipated risk and limited possibility of mechanical control of bleeding, which would have systematically required prophylactic and therapeutic PC transfusions, according to current international recommendations (standard care). Are the trial subjects under 18? yes Number of subjects for this age range: 25 F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25

The purpose of this trial was to assess the ability of eltrombopag to induce sustained treatment-free remission in immune thrombocytopenia purpura (ITP) subjects who relapsed or failed to respond to an initial treatment with steroids.

This project was undertaken by Qilu Hospital of Shandong University and other well-known hospitals in China. In order to report the alteration of Different Immune Parameters in ITP Patients Receiving Eltrombopag Treatment.