Eltrombopag for Adult Idiopathic Thrombocytopenic Purpura (ITP)
Eltrombopag is a highly effective second-line oral thrombopoietin receptor agonist recommended for adults with chronic ITP (≥3 months duration) who remain corticosteroid-dependent or have failed corticosteroids, and it is preferred over rituximab based on current American Society of Hematology guidelines. 1
Indication and Positioning in Treatment Algorithm
For adults with ITP lasting ≥3 months who are corticosteroid-dependent or unresponsive to corticosteroids, eltrombopag (or other TPO-RAs) is suggested over rituximab as second-line therapy. 1 The 2019 ASH guidelines also suggest that TPO-RAs and splenectomy are equivalent options, allowing either choice based on individual patient factors. 1
The 2024 ASH guideline review reaffirmed these recommendations without changes, noting that eltrombopag remains among the preferred TPO-RAs (including romiplostim, avatrombopag, and hetrombopag) for this indication. 1
Mechanism and Efficacy
Eltrombopag works by activating the thrombopoietin receptor through a unique binding site (distinct from endogenous TPO), stimulating platelet production in bone marrow without risk of anti-TPO antibody formation. 1, 2
Clinical trial data demonstrate that 59-70% of patients achieve platelet counts ≥50 × 10⁹/L with eltrombopag 50 mg daily, compared to only 11-16% with placebo. 3, 4 Response typically occurs within 1-2 weeks of treatment initiation. 1
In long-term extension studies with median exposure of approximately 2 years, 85-95% of patients responded at least once, demonstrating sustained efficacy. 1
Dosing and Administration
Start eltrombopag at 50 mg once daily in adults with chronic ITP. 2 After 3 weeks, if platelet counts remain <50 × 10⁹/L, the dose can be increased to 75 mg daily. 3
Monitor platelet counts weekly until stable, then monthly thereafter. 2 Adjust dosing to maintain platelet counts between 50-150 × 10⁹/L to minimize bleeding risk while avoiding excessive thrombocytosis. 3
Critical Administration Considerations
Eltrombopag must be taken on an empty stomach (1 hour before or 2 hours after food) and separated from polyvalent cations (calcium, iron, magnesium, aluminum) by at least 4 hours, as these significantly reduce absorption. 1, 2 This dietary restriction represents a key adherence challenge compared to subcutaneous romiplostim. 1
Comparative Effectiveness: Eltrombopag vs. Romiplostim
The ASH guideline panel determined with very low certainty that there is no net health benefit or harm difference between eltrombopag and romiplostim. 1 Patient preference for route of administration (oral daily vs. weekly subcutaneous injection) should drive the decision. 1
Cost analyses favor eltrombopag: US data estimated total 26-week costs at $66,560 for eltrombopag versus $91,039 for romiplostim, with eltrombopag being less expensive and more effective in preventing bleeding events. 1
Potential for Treatment-Free Remission
Emerging evidence suggests 30% of patients may achieve sustained remission lasting ≥6 months after eltrombopag discontinuation, far exceeding the 9% spontaneous remission rate in untreated chronic ITP. 1 This potential disease-modifying effect may relate to restoration of regulatory T-cell function and immune tolerance. 1
Consider tapering eltrombopag in patients who maintain stable platelet counts (50-100 × 10⁹/L) for at least 6 months without concomitant ITP treatments. 2 Real-world data show 18-32% of patients maintain sustained responses after discontinuation. 1
If relapse occurs after discontinuation, re-introduce eltrombopag at the minimum previously effective dose. 2 Avoid abrupt interruptions or excessive dose adjustments, as these cause platelet fluctuations. 2
Safety Profile and Monitoring Requirements
Hepatotoxicity
Monitor liver function tests at baseline and regularly during treatment, as 13% of patients develop transaminase elevations. 2, 4 This represents the most significant safety concern requiring ongoing surveillance.
Thrombotic Risk
While placebo-controlled trials did not confirm increased thrombotic risk, exercise caution in patients with preexisting thrombotic risk factors (prior thrombosis, malignancy, immobility, oral contraceptives). 1
Bone Marrow Reticulin
Increased bone marrow reticulin formation has been reported in some patients, though clinical significance remains unclear. 2, 4
Rebound Thrombocytopenia
Platelet counts typically return to baseline within 2 weeks after discontinuation, with potential for worsened thrombocytopenia and hemorrhage. 3, 4 Monitor closely during the post-discontinuation period.
Clinical Benefits Beyond Platelet Count
Eltrombopag significantly reduces bleeding events (OR 0.49,95% CI 0.26-0.89; p=0.021) and decreases need for rescue medications compared to placebo. 3 Studies also demonstrate improved quality of life in treated patients. 1
Key Clinical Pitfalls to Avoid
- Failing to account for food and polyvalent cation interactions, which dramatically reduces drug absorption and efficacy 2
- Abrupt discontinuation without tapering, risking severe rebound thrombocytopenia 2, 4
- Inadequate monitoring of liver function, missing early hepatotoxicity 2, 4
- Attempting tapering in patients on anticoagulation unless platelet count ≥100 × 10⁹/L, increasing bleeding risk 2
Decision-Making Framework
When choosing between second-line options for chronic ITP:
- TPO-RA (eltrombopag or romiplostim) is preferred over rituximab based on ASH guidelines 1
- Between eltrombopag and romiplostim: Choose based on patient preference for oral daily (eltrombopag) vs. weekly injection (romiplostim), considering cost favors eltrombopag 1
- TPO-RA vs. splenectomy: Consider patient age, comorbidities, desire to avoid lifelong medication, and timing (delay splenectomy ≥1 year from diagnosis for potential spontaneous remission) 1
The choice should incorporate duration of ITP, bleeding frequency, comorbidities, medication adherence capability, and patient values through shared decision-making. 1