Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: Final results of the EXTEND study

In phase 2/3 trials, eltrombopag treatment of 6 months or less in patients with chronic/ persistent immune thrombocytopenia (ITP) increased platelet counts and reduced bleeding. The open-label EXTEND study evaluated long-term safety and efficacy of eltrombopag in adults with ITP who had completed a previous eltrombopag study. For the 302 patients enrolled, median duration of eltrombopag treatment was 2.37 years (2 days-8.76 years). Median platelet counts increased to 50 3 10⁹/L or more by week 2 and were sustained throughout the treatment period. Overall, 259 patients (85.8%) achieved a response (platelet count ‡50 3 10⁹/L at least once in the absence of rescue), and 133 (52%) of 257 patients achieved a continuous response of 25 weeks or longer. Responses in patients with platelet counts lower than 15 3 10⁹/L, more previous therapies, and/or splenectomy were somewhat lower. Thirty-four (34%) of 101 patients receiving concomitant ITP medication discontinued 1 or more medication. In patients with assessments, bleeding symptoms (World Health Organization grades 1-4) decreased from 57% at baseline to 16% at 1 year. Forty-one patients (14%) withdrew because of adverse events. Hepatobiliary adverse events (n 5 7), cataracts (n 5 4), deep vein thrombosis (n 5 3), cerebral infarction (n 5 2), headache (n 5 2), and myelofibrosis (n 5 2) occurred in more than 1 patient; the remaining adverse events occurred only once. Rates of thromboembolic events (6%) and hepatobiliary adverse events (15%) did not increase with treatment duration past 1 year. EXTEND demonstrated that long-term use of eltrombopag was effective in maintaining platelet counts of 50 3 10⁹/L or more and reducing bleeding in most patients with ITP of more than 6 months’ duration. Important adverse events (eg, thrombosis, hepatobiliary, and bone marrow fibrosis) were infrequent.