Monday, August 22, 2011

Blacks With HCV May Benefit Most From Boceprevir and Telaprevir

Infectious Disease Special Edition

Blacks With HCV May Benefit Most From Boceprevir and Telaprevir
Response Rates Among Blacks Double When New Drugs Are Added to Standard Therapy
by Christina Frangou
Blacks have always lagged behind other patient populations in their response to the standard peginterferon and ribavirin therapy, but the treatment gap between blacks and whites may shrink with the introduction of new therapies. Results vary, but overall studies quote a response rate of 28% among blacks and about half that for white patients.“Some of the most impressive improvements are in African American patients,” said Donald Jensen, MD, professor of medicine and director of the liver center at the University of Chicago. “[In some patients], we’re seeing response rates as high as 50% or more for the first time.”Although blacks represent only 12% of the U.S. population, they make up 22% of the estimated chronic HCV cases. Black men over the age of 50 years have one of the highest HCV rates in the country, with one in seven living with chronic hepatitis C, according to data from the Centers for Disease Control and Prevention. (However, when high-risk behaviors are taken into account, race is not a risk factor for HCV infection [Chou R et al. Ann Intern Med 2004;140:465-479]).

Black patients often have been underrepresented in HCV clinical trials, making it difficult to accurately assess their true response rate. Additionally, some research indicates that blacks respond differently than whites to HCV infection. Despite higher chronic rates of infection, HCV-infected blacks have slower rates of fibrosis progression compared with their white counterparts. At the same time, they have higher rates of progression to liver cancer and poorer responses to therapy.“The major reason for poor response is the genetic polymorphism on chromosome 19 known as IL28B,” said Dr. Jensen. “Although this isn’t the only explanation, it is probably the most important.”In the SPRINT-2 (Serine Protease Inhibitor Therapy 2) trial, investigators found that response rates doubled among blacks when boceprevir was added to standard therapy with peginterferon alfa-2b and ribavirin (Poordad F et al. N Engl J Med 2011;364:1195-1206). In this Phase III, placebo-controlled study, 53% of blacks who received boceprevir plus peginterferon–ribavirin for 44 weeks achieved a sustained virologic response (SVR), representing a substantial rise from the 23% SVR in black patients who received standard interferon and ribavirin alone (P=0.004).

In a modified intention-to-treat analysis, the respective SVR rates among blacks were 26% in the control arm, 47% in the response-guided group and 53% for patients who had full 44-week therapy (P=0.04 and P=0.01, respectively, vs. control arm). Among whites, corresponding response rates were higher at 42%, 70% and 71%, respectively.With telaprevir, black patients also showed marked improvements. In the Phase III ADVANCE trial, published in the June 23 edition of The New England Journal of Medicine, 62% of black patients achieved a viral cure with telaprevir-based treatment, compared with 25% of those treated with standard therapy (Zeuzem S et al. 2011;364:2417-2428).

At this year’s Digestive Disease Week meeting, Steven L. Flamm, MD, professor of medicine and surgery at Northwestern University Feinberg School of Medicine in Chicago, presented results from a pooled analysis of telaprevir Phase III trials, which showed that patients had significant improvements in SVR with the addition of telaprevir, regardless of their race or ethnic status. The SVR among blacks more than doubled, from 25% to 62% after adding telaprevir. For non-blacks, the SVR was 75%—one of the closest reported SVR rates between the two racial groups in studies of hepatitis C therapies.

In Hispanic-Latino patients, SVR rates improved from 45% to 70%, almost identical to the 73% SVR reported among non–Hispanic-Latinos in the treatment arms.Discontinuation rates of all drugs due to adverse events, including rash and anemia, were similar for all patients, regardless of race or ethnicity.According to the pooled analysis, black patients may respond more slowly to treatment than white patients. Nearly 46% of blacks were eligible to receive short-course, 24-week therapy, compared with 65% of the rest of the study cohort. Dr. Flamm said the results are too preliminary and the numbers of patients too few to draw conclusions about whether blacks would benefit from a longer course of treatment. He noted that about 5% more black patients relapsed than non-black patients. Still, he added, “it may be proved eventually that African Americans do need a longer course.”

In its 2010 report on hepatitis and liver cancer, the Institute of Medicine called for greater attention to addressing the special needs of populations at risk, including blacks.
Dr. Jensen reported no relevant disclosures. Dr. Flamm has research grants and is on the speakers’ bureau for Vertex.

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