New Study Challenges Current Thinking About Varied Response to Hepatitis C Treatment in Different Racial Groups

KENILWORTH, N.J. -- Results of a new study

published in 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.(1) 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 percent 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, (2,3,4,5) including the newer peginterferon and ribavirin combination

therapies.(6,7)

"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, MD, assistant

professor of medicine in the Division of Gastroenterology at Duke University Medical

Center in Durham, NC. 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 percent, respectively) as was the rate of discontinuation due to

neutropenia (4 vs. 3 percent, respectively). Neutropenia often is a concern

when treating African Americans, as seen in previous clinical studies.(6,8)

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 percent 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.

"While we are concerned about these findings in African Americans, it is

critical to point out that many of these patients do, in fact, respond to

hepatitis C treatment, so it is vitally important for an infected individual

to aggressively pursue, with their physician, evaluation for therapy," urged

Jonathan McCone, MD, director of the Mount Vernon Endoscopy Center in Alexandria,

Va., and a participating investigator in the study. He noted that hepatitis

C, the most common blood-borne infection in America, affects approximately 4

million people, including a disproportionately high percentage of African

Americans. Chronic hepatitis C infection substantially increases the risk of

cirrhosis and liver cancer, and is the most frequent indication for liver

transplantation among adults. "Timely therapy can help achieve a sustained

virologic response," McCone said, "and patients can improve their chances of

achieving an SVR by adhering to therapy."

Muir concurred, noting that the study found a higher SVR rate (23

percent) among African Americans who completed the full course of therapy.

The importance of adhering to treatment is exemplified by Jackie Boykin,

RN, 41, an African-American woman who contracted hepatitis C in the course

of her work as a nurse. While not a participant in the study by Muir and his

colleagues, she was treated at Duke University Medical Center. In 2002,

Boykin received combination therapy with PEG-INTRON (peginterferon alfa-2b)

Powder for Injection and REBETOL (ribavirin, USP) capsules. She achieved

an SVR and has been virus free for nearly one-and-a-half years. As a result

of her experience, Boykin counsels many patients with hepatitis C to stay with

the therapy "because compliance is so important to treating the disease," she

said.

"I found the Schering-Plough PEG-INTRON Web site very helpful, and the

support I received from the nurses in the Be In Charge program helped me stay

on therapy." Schering-Plough's Be In Charge hepatitis C patient-support

program provides educational materials and telephone contact with registered

nurse counselors skilled in the management of hepatitis C. "Support from

family, the community and medical professionals is critical for hepatitis C

patients," Boykin said. She continues to attend a hepatitis C patient support

group at Duke University Medical Center.

References:

(1) Muir AJ, Bornstein JD, Killenberg PG, for the Atlantic Coast Hepatitis

Treatment Group. Peginterferon alfa-2b and ribavirin for the treatment of

chronic hepatitis C in African Americans and Non-Hispanic Whites. N Engl J

Med 2004; 350(22):27-33.

(2) Reddy KR, Hoofnagle JH, Tong MJ, Lee WM, Pockros P, Heathcote EJ,

Albert D, Joh T. Racial differences in responses to therapy with interferon in

chronic hepatitis C. Hepatology 1999; 30:787-93.

(3) Kinzie JL, Naylor PH, Nathani MG, Peleman RR, Ehrinpreis MN, Lybik M,

Turner JR, Janisse JJ, Massanari M, Mutchnick MG. African Americans with

genotype 1 treated with interferon for chronic hepatitis C have a lower end of

treatment response than Caucasians. J Viral Hepat 2001;8:264-9.

(4) De Maria N. Colantoni A. Idilman R. Friedlander L. Harig J. Van Thiel

DH. Impaired response to high-dose interferon treatment in African-Americans

with chronic hepatitis C. Hepatogastroenterology 2002;49:788-92.

(5) McHutchison JG, Poynard T, Pianko S, Gordon SC, Reid AE, Dienstag J,

Morgan T, Yao R, Albrecht J. The impact of interferon plus ribavirin on

response to therapy in black patients with chronic hepatitis C.

Gastroenterology 2000;119:1317-23.

(6) Howell CD, Jeffers LS, Hu S, Lopez-Talavera JC. Safety and adherence

to peginterferon alfa-2a (40KD) plus ribavirin (RBV) in black Americans with

chronic hepatitis C (CHC) HCV genotype 1. Poster presentation M1236 (Abstract

No. 106885) at Digestive Disease Week, New Orleans, LA, May 15-20, 2004.

(7) Jeffers LJ, Cassidy W, Howell C, Reddy R, Sheridan S, Ho I, Khouri S,

Harb G. Peginterferon alfa-2a (40kd) (Pegasys) in combination with ribavirin

in African American and Caucasian patients with chronic hepatitis C virus

genotype 1: results of a multicenter study. Abstract 71, oral presentation

at: 54th annual meeting of the American Association for the Study of Liver

Diseases, Boston, MA, October 24-28, 2003.

(8) Howell C, Jeffers LJ, Cassidy W, Reddy R, Sheridan S, Ho I, Khouri S,

Harb G. Peginterferon alfa-2a (40kd) (Pegasys) in combination with ribavirin

in African American and Caucasian patients with chronic hepatitis C HCV

genotype 1: safety and tolerability. Abstract 332, poster presentation at:

54th annual meeting of the American Association for the Study of Liver

Diseases, Boston, MA, October 24-28, 2003.

Source: Schering-Plough Corporation