Background
Phase 3 double-blind placebo-controlled RCT (RAISE). 197 adults with chronic ITP (duration ≥12 months), platelet count <30×10⁹/L, and ≥1 prior ITP treatment. Patients could remain on stable concomitant ITP therapy (corticosteroids, azathioprine, or danazol). Eltrombopag (Promacta/Revolade) is a small-molecule thrombopoietin receptor (c-Mpl) agonist that stimulates megakaryocyte proliferation and platelet production. Randomized 2:1. Primary phase 6 months.
Interventions and follow up
Arm A: Eltrombopag 50 mg orally once daily, with dose adjustments to 75 mg/day or reduction based on platelet response (target 50–200×10⁹/L)
Arm B: Placebo orally once daily
Primary endpoint: Proportion of treatment weeks with platelet counts 50–400×10⁹/L during weeks 1–26
mFollow up: 26 week
Arm B: Placebo orally once daily
Primary endpoint: Proportion of treatment weeks with platelet counts 50–400×10⁹/L during weeks 1–26
mFollow up: 26 week
Results
Weeks with platelet response: 59% (eltrombopag) vs 16% (placebo), P<.0001
Any response (platelet ≥50×10⁹/L) during study: 79% vs 28%, P<.0001
Bleeding symptom reduction: WHO grade ≥2 bleeding 39% (eltrombopag) vs 60% (placebo), P=.002
Rescue medication use: 18% (eltrombopag) vs 40% (placebo)
Any response (platelet ≥50×10⁹/L) during study: 79% vs 28%, P<.0001
Bleeding symptom reduction: WHO grade ≥2 bleeding 39% (eltrombopag) vs 60% (placebo), P=.002
Rescue medication use: 18% (eltrombopag) vs 40% (placebo)
Adverse events
Main adverse events: Headache 21% vs 20%, nasopharyngitis 14% vs 13%, nausea 13% vs 9%. ALT elevation grade ≥3: 5% vs 0%. Thromboembolic events: 3 (eltrombopag) vs 0 (placebo) — numerically higher but small numbers. Bone marrow fibrosis: not observed in 6-month study. No hepatotoxicity necessitating withdrawal in majority. Discontinuation due to AEs: 3% vs 0%.
Conclusions
Eltrombopag maintained platelet counts ≥50×10⁹/L in 59% of treatment weeks versus 16% on placebo, with significant reduction in bleeding symptoms, establishing eltrombopag as an effective TPO-RA for chronic ITP.
Key Limitations
Key Limitations: Allowed concomitant ITP therapy (up to 31% on corticosteroids) makes it difficult to isolate eltrombopag effect. 26-week primary analysis only; durability on longer treatment unproven in this trial. Thromboembolic events (3 vs 0) require continued surveillance. Rebound thrombocytopenia on discontinuation is a clinical concern. Not all patients respond; ~21% achieved zero responsive weeks. ALT monitoring required throughout treatment.
Clinical Context
FDA approved November 2008 (Promacta) for chronic ITP — the first TPO-RA approved for ITP. Extended to aplastic anemia (2014) and MDS (2023). RAISE demonstrated that non-immunosuppressive platelet production stimulation can maintain platelet counts in chronic ITP. Now a standard second-line therapy alongside romiplostim. Choice between eltrombopag (oral) and romiplostim (SC weekly) is often patient-preference driven. Real-world data show durable responses in some patients with remission after discontinuation (~15–20%).
References