What is the use of Eltrombopag (thrombopoietin receptor agonist) in patients with low platelet counts, specifically in chronic immune thrombocytopenia purpura (ITP)?

Eltrombopag for Chronic Immune Thrombocytopenia Purpura (ITP)

Eltrombopag is highly effective as a second-line therapy for chronic ITP patients with low platelet counts, increasing platelet counts to safe levels (≥50 × 10^9/L) in approximately 59% of patients compared to 16% with placebo. 1

Mechanism and Indication

• Eltrombopag is an oral, non-peptide thrombopoietin receptor agonist (TPO-RA) that stimulates thrombopoiesis, leading to increased platelet production 2
• It is FDA-approved for chronic ITP patients who have failed initial treatments with traditional immune modulators or splenectomy 3
• Eltrombopag works by activating the thrombopoietin receptor, which is the primary regulator of platelet production 3

Dosing and Administration

• Initial recommended dose is 50 mg once daily for adult patients with chronic ITP 4
• Monitor platelet counts weekly until a stable count is achieved 4
• If platelet count remains <50 × 10^9/L after 2-3 weeks, increase dose to 75 mg once daily (maximum dose) 4
• If platelet count exceeds 200 × 10^9/L, reduce the dose by 25 mg 4
• If platelet count exceeds 400 × 10^9/L, temporarily discontinue eltrombopag and resume at a reduced dose when platelet count falls below 150 × 10^9/L 4
• Take eltrombopag on an empty stomach (1 hour before or 2 hours after meals) as food significantly reduces absorption 4
• Avoid calcium-rich foods or supplements within 4 hours of taking eltrombopag 4

Efficacy in Chronic ITP

• Response to eltrombopag typically occurs within 1-2 weeks of initiating therapy 4, 1
• By day 15, more than 80% of patients receiving 50 or 75 mg of eltrombopag daily show increased platelet counts 4
• In the RAISE study, 60% of patients treated with eltrombopag achieved a sustained platelet response compared to only 10% with placebo 5
• Patients treated with eltrombopag had significantly fewer bleeding events compared to placebo (odds ratio 0.49,95% CI 0.26-0.89) 1
• Eltrombopag reduces the need for rescue therapy in ITP patients (18% vs 40% with placebo) 5
• Among patients receiving concomitant ITP therapy at baseline, 59% of those treated with eltrombopag were able to discontinue these medications 5

Potential for Treatment-Free Remission

• While TPO-RAs were initially considered a maintenance therapy, studies have shown that some patients can achieve stable responses after discontinuation 3
• In various studies, 3-48% of patients maintained responses after discontinuation of eltrombopag 3
• A retrospective analysis from Spain showed that among 260 adult primary ITP patients receiving eltrombopag, 26 of 33 patients (79%) who discontinued due to stable response maintained sustained responses over a median follow-up of 9 months 3
• Patients with stable platelet counts (50-100 × 10^9/L) for at least 6 months without concomitant treatments may be candidates for tapering and discontinuation 3
• For tapering, a gradual approach is recommended: reduce eltrombopag by 25 mg every 2 weeks, then consider 25 mg every other day before complete discontinuation 4

Monitoring Requirements

• Check platelet counts weekly until stable, then monthly 4
• Monitor liver function tests at baseline and regularly during treatment, as 13% of patients may develop liver function abnormalities 4, 3
• Assess for signs of bone marrow reticulin formation if treatment failure or new cytopenia develops 4
• Evaluate for thromboembolic events, particularly in patients with risk factors 4, 6

Safety Considerations

• Headache is the most common adverse event (occurring in >20% of patients) 4
• Liver function test abnormalities were seen in 13% of eltrombopag-treated patients 3
• Increased bone marrow reticulin has been reported in some patients 3
• Patients with thromboembolism risk factors should be treated with caution due to potential prothrombotic risk 6
• Discontinue tapering if platelet levels fall below 30 × 10^9/L or below 50 × 10^9/L if bleeding events occur 3

Special Considerations

• Patients receiving anticoagulant therapies should not be eligible for tapering unless a platelet count of at least 100 × 10^9/L is reached 3
• If relapse occurs after discontinuation, re-introduction of the same TPO-RA (eltrombopag) at the minimum effective dose is recommended 3
• Some patients may require long-term treatment, especially those with longer disease duration or multiple prior therapies 7
• Recent research suggests that combining eltrombopag with pulsed dexamethasone as first-line therapy may result in durable responses off therapy in a significant number of ITP patients (56.5%) 8

Common Pitfalls to Avoid

• Abrupt interruptions or excessive dose adjustments may cause platelet fluctuations and should be avoided 3
• Patients requiring maximal doses for prolonged periods to maintain stable platelet counts may not be ideal candidates for treatment tapering 3
• Not accounting for food interactions can significantly reduce drug absorption and efficacy 4
• Failing to monitor liver function tests regularly may miss hepatotoxicity, particularly in patients with pre-existing liver disease 4