Bleeding is of particular clinical importance in the management of chronic
immune thrombocytopenia (
ITP), which involves impaired platelet production and accelerated destruction. We report the first comprehensive analysis of the impact of
eltrombopag on
bleeding in five clinical studies of adult chronic
ITP: two 6-week phase 2 (TRA100773A) and phase 3 (TRA100773B) studies; a 6-month phase 3 study (RAISE); a phase 2 repeat-dose study (REPEAT); and a phase 3 extension study (EXTEND).
Bleeding was assessed using the World Health Organization
Bleeding Scale and categorized as no
bleeding (grade 0), any
bleeding (grades 1-4), and clinically significant
bleeding (grades 2-4).
Bleeding was also assessed using National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Across all studies,
bleeding at baseline ranged from 50 to 73% for
eltrombopag-treated patients; by week 2,
bleeding had decreased, ranging from 26 to 39%. This trend was maintained throughout treatment. Similar results were observed for clinically significant
bleeding. No such trend was seen in placebo-treated patients for any
bleeding or clinically significant
bleeding. For TRA100773B and RAISE, the odds of any
bleeding across the entire treatment period were 51 and 76% lower for
eltrombopag-treated versus placebo-treated patients (P=0.021, P<0.001). The odds of clinically significant
bleeding in RAISE were 65% lower (P<0.001). In conclusion, analysis of prospective data from five clinical studies demonstrates that
eltrombopag significantly reduces
bleeding in adult patients with chronic
ITP.