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SAN FRANCISCO — Patients with severe idiopathic thrombocytopenic purpura were eight times more likely to achieve target platelet counts when treated for 6 months with oral eltrombopag in a randomized, placebo-controlled, phase III trial presented at the annual meeting of the American Society of Hematology.

Eltrombopag (Promacta) reduced the odds of bleeding by 76% and of clinically significant bleeding by 65%, vs. placebo. It also lessened the need for rescue medications and concomitant medications in patients with chronic idiopathic thrombocytopenic purpura (ITP) not responsive to previous therapy.

No safety concerns emerged in RAISE (Randomized Placebo-Controlled ITP Study With Eltrombopag), a 197-patient trial sponsored by GlaxoSmithKline and designed to evaluate long-term use of the agent. Adverse events were minor and similar with eltrombopag and placebo.

For patients who are “refractory to the conventional therapy or suffering from the side effects, there is now new hope and a new treatment,” principal investigator Dr. Gregory Cheng of the Chinese University of Hong Kong said at a press briefing.

The availability of eltrombopag and romiplostim (AMG-531, Nplate), another new thrombopoietin receptor agonist, represents “a huge change” in thinking about ITP and will greatly benefit patients, according to Dr. Sherrill J. Slichter, an investigator at the briefing, who was not involved in the eltrombopag study and who emphasized that she has no stock in the companies behind these new drugs.

“It has been an enormous boon to the management of these patients to be able to show that some of the ones who fail immunosuppressive therapy in fact respond to an agent that increases platelet production,” said Dr. Slichter of Puget Sound Blood Center for the National Heart, Lung, and Blood Institute Transfusion Medicine/Hemostasis Clinical Trials Network in Seattle. Stopping eltrombopag leads to a reduction in platelet counts, she said: “So it is not a cure, but it is a treatment.”

Still, despite enthusiasm for Dr. Cheng's results, neither Dr. Slichter nor Dr. Kenneth Kaushansky, president of ASH, was ready to use eltrombopag in patients who still have other options. Indeed, Dr. Kaushansky, chair of the department of medicine at the University of California, San Diego, predicted that hematologists would be slow to adopt eltrombopag and romiplostim.

“We have not seen significant side effects so far from thrombopoietin-stimulating agents,” he said. “But we don't have years and tens of thousands of experiences yet. Once we begin to see [that] the side effect profile of those agents is not significant, then I think confidence will grow in those agents, and I think we will see those agents used earlier.”

Dr. Cheng agreed that, in his own practice, he still reserves eltrombopag for chronic patients who have failed to respond to other proven therapies. “My first line of therapy will still be corticosteroids,” he said, concurring that potentially curative treatments, including splenectomy, should be tried before potentially lifelong treatment with eltrombopag.

An exception might be an ITP patient scheduled for surgery, Dr. Cheng suggested. Currently, the patient might be admitted to a hospital for preparation with intravenous immunoglobulin, but 2 weeks of oral eltrombopag therapy could be an outpatient alternative. “Then they have the surgery and can stop the medication afterward,” he said.

RAISE randomized adults with platelet counts below 30,000 mcL who had failed at least one other ITP therapy. While 135 patients received a starting dose of 50 mg of eltrombopag once daily, another 62 patients received a placebo. Depending on response, the trial allowed titration of the eltrombopag dose up or down in a range of 25–75 mg once a day.

Investigators set the primary end point as achieving platelet counts between 50,000 and 400,000 mcL. Dr. Cheng said that 75% of the eltrombopag cohort reached target, vs. 28% of those on placebo. This was true regardless of splenectomy status. The odds ratio for achieving a response with eltrombopag was 8.2.

Median counts were 16,000 mcL in both cohorts before the initiation of treatment, and never went above 30,000 mcL in the placebo group, according to data released by GlaxoSmithKline. In the eltrombopag cohort, it rose to 36,000 mcL after 1 week, and thereafter ranged from 52,000 mcL to 91,000 mcL during the study. The median returned to baseline within 2 weeks of stopping eltrombopag at the end of the study.

Secondary end points favoring eltrombopag included more patients stopping or reducing simultaneous ITP medications (59% vs. 32%) and fewer patients needing rescue therapy (19% vs. 40%).

Dr. Cheng disclosed being a consultant to and receiving honoraria from GlaxoSmithKline. His coinvestigators included employees of the company and holders of equity ownership.

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'There is now new hope and a new treatment' for ITP patients refractory to conventional treatment. DR. CHENG

Eltrombopag Increases Platelet Counts in Chronic ITP