Results of a new study published in the current issue of the New England Journal of Medicine show that in patients who have chronic hepatitis C, genotype 1 -- the most common form of the disease and difficult to treat successfully -- non-Hispanic whites achieved one of the highest response rates reported to date, but response rates in African Americans were significantly lower.
The findings challenge much of the current thinking about why African Americans respond less well to hepatitis C treatment and underscore the need for further clinical research.
In the large open-label study, non-Hispanic white patients achieved a sustained virologic response (SVR) rate of 52 percent, which was significantly higher than the 19 per cent seen in African American patients (p < 0.001). SVR is the sustained undetectability of the hepatitis C virus for six months following therapy. Lower SVR rates in African Americans, as seen in this study, also have been seen in past studies using other forms of interferon therapy, including the newer peginterferon and ribavirin combination therapies.
"The sustained virologic response rates achieved in this study in genotype 1 patients demonstrate that peginterferon alfa-2b and ribavirin combination therapy is effective," said lead investigator Andrew Muir, M.D., assistant professor of medicine, Division of Gastroenterology, Duke University Medical Center, Durham, North Carolina. He noted that the study was conducted in a "real-world" community setting, rather than in a more restrictive clinical trial. "However, the lower response rate in African Americans poses a critical challenge because even with the best therapies currently available, African American patients clearly have a lower response rate."
In the study, 100 African American and 100 non-Hispanic white patients with chronic hepatitis C, genotype 1, were treated with a regimen of peginterferon alfa-2b (1.5 mcg/kg/weekly) and 1,000 mg of ribavirin daily for the first 12 weeks and then 800 mg daily thereafter, for a total of 48 weeks. Growth factors were not used. The current U.S. label for peginterferon alfa- 2b (1.5 mcg/kg/week) recommends that it be used in combination with 800 mg of ribavirin daily. The investigators analyzed a number of variables, including patients' socio-demographic and clinical characteristics, and found that only race was significantly associated with the difference in SVR rates.
The study demonstrated the safety and tolerability of peginterferon alfa- 2b and ribavirin combination therapy in these patients, and showed that the rates and types of adverse events were similar in the African American and non-Hispanic white patient groups. Importantly, the rate of dose reduction of peginterferon alfa-2b because of neutropenia was similar in the two groups (13 vs. 14 per cent, respectively) as was the rate of discontinuation due to neutropenia (4 vs. 3 per cent, respectively). Neutropenia often is a concern when treating African Americans, as seen in previous clinical studies.
Dr. Muir said the reasons for the different responses seen in the racial groups remains unknown, but the study results counter at least some previously held hypotheses. For example, some suggested the disparity could be due to a higher prevalence of hepatitis C, genotype 1, in African Americans, but in this study 98 per cent of both racial groups had that form of the virus. Further analyses showed that other variables -- including age, sex, education, body weight, initial viral load, duration of HCV infection and other clinical factors -- had no significant effect on response.
"Showing these other factors are not the reason for the difference in response rates adds to our understanding of the disease and is important in furthering research to identify what factors actually are responsible. We can speculate about what those causes might be, but we need additional clinical studies to get real answers," he said.