HAMPTON ROADS, VA — The recent Food and Drug Administration approval of eltrombopag to boost thrombocytopenia, or low platelet counts, in patients with hepatitis C virus (HCV) may permit thousands more veterans to start standard therapy for the disease.
And, for those patients who cannot tolerate interferon even with higher platelet counts, two recent studies provide hope of alternative treatments in the coming years.
Nearly 150,000 veterans in VHA care have hepatitis C. About 13% of them — or about 19,000 veterans — have developed cirrhosis as a complication of their hepatitis. For many cirrhotics, thrombocytopenia has prevented treatment of HCV.
“Patients with cirrhosis, complicated by thrombocytopenia, are in the greatest need of treatment for hepatitis C,” Mitchell Shiffman, MD, director of the Liver Institute of Virginia at Bon Secours Health Systems told U.S. Medicine. “If they can’t be treated, they must wait until their liver deteriorates enough to get a transplant.”
A recent study of 467 patients found that 7.6% of HCV infected individuals had thrombocytopenia.1 A 2010 review of 27 studies suggested that the rate might be 24% or higher.2
Severe thrombocytopenia is considered a contraindication for use of interferon, because the drug suppresses platelet development. Even patients with moderate thrombocytopenia might not be good candidates for standard HCV therapy because of the risk of interferon-induced thrombocytopenia that could require termination of therapy or reductions in dosage.
“Patients with severe thrombocytopenia and cirrhosis cannot afford to have therapy managed with dose reduction, because the effectiveness of treatment is substantially impaired,” said Shiffman. “The approval of eltrombopag allows us to pharmacologically increase platelet counts so that we can initiate and maintain treatment in patients who could not otherwise be treated and achieve a sustained virologic response.”
Eltrombopag stimulates proliferation of megakaryocytes, platelet precursor cells. The FDA first approved it for use in treating idiopathic thrombocytopenic purpura in 2008.
In extending the drug’s approval, FDA cited the Phase 3 clinical trials ENABLE 1 and 2 (Eltrombopag to INitiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C-related Liver Disease), that demonstrated that eltrombopag allowed patients to initiate and maintain therapeutic doses of pegylated interferon and ribavirin, the dual therapy standard at the time of the studies. The two studies together enrolled more than 1,500 patients. ENABLE 1 utilized peginterferon alfa-2a plus ribavirin for antiviral treatment; ENABLE 2 utilized peginterferon alfa-2b plus ribavirin.
Eltrombopag has not been tested with the currently recommended triple therapy, in which the protease inhibitors boceprevir or telaprevir are added to interferon and ribavirin.
“With the triple therapy, the problem with thrombocytopenia is still present, and low platelet count would be contraindicated without a platelet growth factor,” said Shiffman, who was a principal investigator in the eltrombopag trials. “While the studies did not look at the triple-therapy treatment, neither of the protease inhibitors affects the platelet count, and I would certainly use eltrombopag in the same way for the current therapy.”
As part of the VA National Formulary process, Pharmacy Benefits Management (PBM) Services will be reviewing eltrombopag’s recently approved FDA indication for the treatment of thrombocytopenia in patients with chronic hepatitis C to allow for the initiation and maintenance of interferon-based therapy.
According to VA spokeswoman Meagan Lutz, “The evidence review will determine if any changes in VA’s treatment guidance are warranted. In the interim, VA providers continue to actively treat veterans infected with hepatitis C virus, without contraindications to treatment, in accordance with VA and American Association for the Study of Liver Diseases (AASLD) guideline recommendations.”
Eltrombopag is not without risks. The drug may cause hepatotoxicity and, when combined with interferon and ribavirin in HCV treatment, may increase the risk of liver decompensation. As a result, the drug contains a boxed warning that eltrombopag should only be used in patients whose thrombocytopenia is so severe that they could not otherwise start interferon-based HCV therapy.