Background
Open-label single-arm long-term extension (EXTEND). N=302 adults with persistent/chronic ITP who completed ≥1 prior eltrombopag study (RAISE, REPEAT, SURGE, TRA102537). Conducted Jun 2006 - Jul 2015. Goal: characterize safety, tolerability, efficacy of eltrombopag with up to 8+ yr exposure in chronic ITP.
Interventions and follow up
Treatment: Eltrombopag 50 mg PO daily (titrated 25-75 mg by platelet count) in adults with persistent/chronic ITP previously enrolled in a parent eltrombopag study
Primary endpoint: Long-term safety and tolerability
mFollow up: Median eltrombopag treatment 2.37 yr (range 2 days-8.76 yr)
Primary endpoint: Long-term safety and tolerability
mFollow up: Median eltrombopag treatment 2.37 yr (range 2 days-8.76 yr)
Results
Platelet response (≥50×10⁷/L at least once): 85.8% (259/302)
Continuous response (≥25 wk duration): 52% (133/257 evaluable)
Concomitant ITP medication discontinued: 34% of 101 patients on baseline concomitant therapy
Bleeding reduction (WHO grade 1-4): 57% at baseline → 16% at 1 yr
Continuous response (≥25 wk duration): 52% (133/257 evaluable)
Concomitant ITP medication discontinued: 34% of 101 patients on baseline concomitant therapy
Bleeding reduction (WHO grade 1-4): 57% at baseline → 16% at 1 yr
Adverse events
Discontinuation due to AEs: 14% (41/302)
Hepatobiliary (any grade): 15% — mostly asymptomatic ALT/AST elevations; no increase beyond yr 1
Thromboembolic events: 6% (DVT n=3, cerebral infarction n=2, PE n=2, others)
Other: cataracts 4 patients; bone marrow fibrosis (reticulin/collagen) 2 patients
Deaths: 6 (none investigator-attributed to drug); no new/unexpected signals with prolonged use
Hepatobiliary (any grade): 15% — mostly asymptomatic ALT/AST elevations; no increase beyond yr 1
Thromboembolic events: 6% (DVT n=3, cerebral infarction n=2, PE n=2, others)
Other: cataracts 4 patients; bone marrow fibrosis (reticulin/collagen) 2 patients
Deaths: 6 (none investigator-attributed to drug); no new/unexpected signals with prolonged use
Conclusions
Long-term eltrombopag maintains platelet counts ≥50×10⁷/L and reduces bleeding in most patients with persistent/chronic ITP, with a stable safety profile over years and no new toxicities beyond yr 1.
Key Limitations
Open-label single-arm extension with no comparator and selection bias (enrolled prior responders/tolerators). Variable exposure duration and dropout limit long-term-toxicity inference; hepatobiliary, thromboembolic, and marrow-fibrosis signals warrant ongoing monitoring.
Clinical Context
Eltrombopag is an FDA/EMA-approved oral TPO receptor agonist for chronic ITP after insufficient response to corticosteroids/IVIG/splenectomy. ASH ITP guidelines endorse TPO-RAs (eltrombopag, romiplostim, avatrombopag) as preferred second-line; EXTEND supplies the durability/safety evidence supporting indefinite use.