Pharmacy & Therapeutics - February 2009 - (Page 100)

MEETING HIGHLIGHTS: American Society of Hematology Long-Term Oral Eltrombopag (Promacta) in Chronic Idiopathic Thrombocytopenic Purpura • Gregory Cheng, MD, Chinese University of Hong Kong, Hong Kong, China With standard intravenous (IV) treatment for idiopathic thrombocytopenic purpura (ITP) requiring two to five days of inpatient treatment, the convenience of oral eltrombopag (Promacta, GlaxoSmithKline) is likely to give this agent a clinical role, according to Dr. Cheng, lead investigator of RAISE (RAndomized placebo-controlled ITP Study with Eltrombopag) In chronic ITP, low blood platelet counts caused by increased platelet destruction or inadequate platelet production persist and can last indefinitely. Increased bleeding risk, along with excessive bruising, is a consequence. Serious hemorrhages, on rare occasions, are fatal. Eltrombopag is the first approved, oral small-molecule, nonpeptide thrombopoietin receptor agonist. In preclinical research and clinical trials, eltrombopag stimulated the proliferation and differentiation of megakaryocytes, the bone marrow cells that give rise to blood platelets. RAISE included 197 patients with platelet counts below 30,000 mcL. Patients received once-daily eltrombopag at 25 to 75 mg (initially at 50 mg, with dosing individualized based on response) or placebo for six months. About 50% of the enrolled patients had platelet counts below 15,000/mcL, and the other half had received at least three previous ITP medications. Platelet counts of 50,000 to 400,000 mcL were achieved by 75% of patients receiving eltrombopag compared with 25% receiving placebo (P < 0.001). Eltrombopag also reduced the incidence and severity of bleeding. The odds of bleeding and significant bleeding were reduced by 76% with eltrombopag and by 65% with placebo. Baseline variables of prior splenectomy, platelet count, and ITP medications did not affect outcomes. The need for rescue or concomitant medications (predominantly corticosteroids) was reduced significantly, and health-related quality of life also improved (P < 0.05). Eltrombopag was generally well tolerated. Adverse events leading to treatment withdrawal were experienced similarly between eltrombopag and placebo patients. Nausea and vomiting were more common with eltrombopag, as were liverrelated adverse events (12% vs. 8% for placebo). Thromboembolic events were reported in 1.5% of patients receiving eltrombopag but in none of the placebo patients (0%). Dr. Cheng concluded, “As compared with those receiving placebo, patients with chronic ITP were able to generate sustained platelet counts significantly more often with eltrombopag.” In an interview, he added, “Eltrombopag will have a role among patients refractory to conventional ITP treatment and among elective surgery ITP patients.” firmed the chelation agent’s efficacy for removing cardiac iron. About 70% of patients with beta-thalassemia, which is endemic in the world’s malaria belt, die of heart failure related to iron overload. A beta-thalassemia patient receiving 2 to 3 units of blood monthly is taking on an iron load of 600 to 700 mg each month and needs daily chelation, Dr. Pennell said in an interview. He reported on the cardiac substudy of the EPIC trial. In patients with beta-thalassemia, cardiac T2* magnetic resonance imaging (MRI) evaluates myocardial iron content and correlates with reduced left ventricular (LV) ejection fraction. Myocardial T2* values below 20 msec are indicative of iron overload. The cardiac substudy included patients who had MRI myocardial T2* between 5 and 20 msec, LV ejection fraction (LVEF) of 56% or above, serum ferritin above 2,500 ng/mL, increased MRI transverse relaxation rate (R2) liver iron concentration (above 10 mg of iron per gram, dry weight) and a lifetime minimum of 50 transfused blood units. Deferasirox was initiated at 30 mg/kg per day, and subsequent dose adjustments of 5 to 10 mg/kg per day were based on changes in serum ferritin, cardiac T2* at six months, and safety parameters. The primary endpoint was the change in myocardial T2* from baseline to one year. Among 114 patients, the mean baseline liver iron concentration was 28.2 ± 10.0 mg of iron per gram (dry weight). Median serum ferritin was 5,235 ng/mL, and the mean amount of transfused blood in the previous year was 185 mL/kg. Most patients (68.4%) had received chelation with injected desferrioxamine (deferoxamine, or DFO, Novartis) or combined DFO/deferiprone (Ferriprox, Apo Pharma) (31.6%). The mean deferasirox dose over the one-year treatment period was 32.6 mg/kg per day. At one year, myocardial T2* improved significantly from a baseline of 11.2 mg to 12.9 msec (P < 0.0001), representing an increase by a factor of 1.16 from baseline. Increases of more than 4% in T2* were seen in 69.5% of patients. There was no change in 14.3% of the patients, but worsening occurred in 16.2%). Increases in T2* were similar in subgroups with severe and mild-to-moderate iron overload. LVEF remained stable throughout the study. At one year, mean liver iron levels were significantly reduced in the overall population (P < 0.0001) and in subgroups. Also, median serum ferritin decreased significantly from baseline (5,235 ng/mL) by –1257 ng/mL and in the subgroups. Deferasirox was generally well tolerated, and most adverse events were mild to moderate. “Showing that this oral iron chelator works is good news for patients,” Dr. Pennell said. Deferasirox (Exjade) Reduces Cardiac Iron in BetaThalassemia Major: Cardiac Substudy of EPIC • Dudley Pennell, MD, Royal Brompton Hospital, London, U.K. EPIC, the first prospective, multicenter study of deferasirox (Exjade, Novartis) in beta-thalassemia patients with mild, moderate, and severe myocardial siderosis (iron overload), con- 100 P&T® • February 2009 • Vol. 34 No. 2

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Pharmacy & Therapeutics - February 2009 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Pushing an Expanded Role for Pharmacists Better Asthma Management with Advanced Technology Pharmaceutical Approval Update 58th Annual Meeting, American Society of Human Genetics, 2008 American Society of Hematology, 50th Annual Meeting and Exposition 2008 San Antonio Breast Cancer Symposium Stahl’s Essential Psychopharmacology, 3rd Edition Author Guidelines

Pharmacy & Therapeutics - February 2009

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