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Chronic immune thrombocytopenic purpura (ITP) is a relatively uncommon autoimmune bleeding disorder, affecting 10,000 to 20,000 Americans each year. ITP is caused by antiplatelet antibodies that destroy circulating blood platelets as well as inhibit bone marrow production of platelets. The condition is characterized by increased bruising, chronic nosebleeds, blood in stool or urine, and other serious bleeding events, including the risk of brain hemorrhage.

Although the disease is a potentially life-threatening condition, ITP patients are often hesitant to continue treatment due to the potentially harsh side effects of available therapeutic options.

A Different Approach to Treatment

Of all ITP-related deaths, research suggests that half are due to low platelet counts while the other half occur from complications of treatment. Corticosteroids, the traditional pharmacotherapy treatment for ITP, usually produce an increase in platelet count, but have significant side effects, including diabetes, osteoporosis, weight gain, and infections. However, corticosteroids rarely keep the platelet count elevated once they are discontinued. Alternative chronic therapies, such as immunosuppressive or chemotherapy drugs, have a lower rate of response and decrease the ability of the immune system to resist infection. The removal of the spleen is another treatment option for ITP; however, splenectomy offers only a 60% long term success rate and may be associated with rare fatal bacterial infections. The adverse side effects of current ITP therapy often complicate treatment decisions for physicians and patients alike.

Currently available ITP treatments are designed to reduce platelet destruction and may be ineffective in some patients. To improve therapy, clinicians have taken a different approach in which the focus is on increasing the rate of platelet production. In ITP, the level of thrombopoietin (a natural regulator of platelet production) does not rise adequately to stimulate the production of more blood cells. Two new therapies mimic the function of thrombopoietin by binding to different locations on the thrombopoietin receptor to simulate increased platelet production. The first, romiplostim, is a unique peptibody given as weekly injections. The second, eltrombopag, is an oral drug taken daily.

Romiplostim was recently submitted for FDA approval for treatment of adults with chronic ITP who have not undergone splenectomy and have had an inadequate response or are intolerant to traditional therapy for patients who have undergone splenectomy and have an inadequate response to the procedure.

Analyzing New Study Data

In the February 2, 2008 issue of the Lancet, my colleagues and I described the results of a 24-week phase III trial with romiplostim in the treatment of splenectomized and non-splenectomized patients with ITP. We found an overall platelet response rate to romiplostim of 88% in non-splenectomized patients and 80% in splenectomized patients. As a result, many patients were able to reduce or discontinue other ITP medications. Observed side effects were mild, consisting of dizziness and headache in some patients. Although showing a high continuous rate of response, romiplostim is not a cure for ITP; discontinuing the weekly injections will result in platelet counts returning to a low level.

The low toxicity and high response rate to romiplostim may provide a new therapeutic option for ITP that turns a potentially life-threatening condition into one more easily managed with a weekly injection. Eltrombopag may also prove to be another treatment option for the condition. We’re seeing dramatic results with these new drugs to treat ITP and hope to investigate the benefits of these new stimulators of platelet production in other conditions with reduced platelet production, such as cancer chemotherapy or chronic hepatitis C infection.

Dr. Kuter has indicated to Physician’s Weekly that he has or has had the following financial interests: Amgen, GlaxoSmithKline, AKARx, Ligand Pharmacueticals, and MGI Pharma.