A new, large clinical trial of people with a common form of hepatitis B (HBV) has found that therapy with Pegasys (peginterferon alfa-2a), a common treatment prescribed for those with hepatitis C (HCV), can sustain longer-term responses compared to Epivir-HBV (lamivudine), a current standard therapy for HBV. But one expert commenting on the study says all the treatment options for hepatitis B are still "less than ideal".
The findings are published in the June 30 edition of the New England Journal of Medicine.1
Success Indicator: Seroconversion
"Treatment success in this study is measured by hepatitis B e antigen seroconversion, and these results demonstrate that more patients achieved seroconversion when treated with Pegasys than with lamivudine," said Michael Fried, MD, a professor of Gastroenterology and Hepatology at the University of North Carolina at Chapel Hill and one of the study's researchers.
Seroconversion is a process by which people with hepatitis B convert from having no antibodies against HBV to having the antibodies. A protein produced by the hepatitis B virus known as the hepatitis B envelope antigen (HBeAg) signals the antibodies to attack. Thus, levels of HBeAg serve as an indicator to your doctor that the virus is present and actively replicating, or making copies of itself.2
Going Head-to-Head
Chief investigator George Lau, MD, assistant dean with the Faculty of Medicine at the University of Hong Kong, along with Fried and their colleagues recruited more than 800 patients for the Phase 3 clinical trial to compare the safety and efficacy of Pegasys plus Epivir, Pegasys plus a non-therapeutic placebo, or Epivir alone as therapy for the disease. Each patient was classified as HBeAg-positive, a classic form of active hepatitis B, and had genotypes B or C.
The patients were assigned at random to one of the three treatment groups, and therapy continued for 48 weeks, followed by a 24-week follow-up period.
At the end of follow-up, significantly more patients who had received either Pegasys monotherapy or Pegasys combined with Epivir had HBeAg seroconversion or large reductions in HBV DNA—the virus' genetic material that serves as evidence of its existence in the body—compared to those receiving Epivir monotherapy. More specifically, nearly a third of those who had taken Pegasys alone responded to treatment (HBeAg seroconversion) versus 19 percent taking Epivir monotherapy. Additionally, 27 percent of those taking combination treatment responded versus 19 percent taking Epivir alone. HBV DNA levels plunged (below 100,000 copies per mL) in 32 percent of those who had taken Pegasys alone versus just over one-fifth of those taking Epivir monotherapy. Thirty-four percent of those given the combination therapy had reductions in HBV DNA, Lau and his team reported.
Additionally, 16 patients given Pegasys alone or in combination had evidence of hepatitis B surface antigen (HBsAg) seroconversion compared to none of the men and women who had been taking Epivir alone. (HBsAg is another antigen whose levels tend to rise in the bloodstream before the onset of clinical symptoms. This is also used as a biological marker of HBV infection.) "HBsAg loss or seroconversion is considered the ultimate therapeutic goal of anti-HBV therapy," wrote Lau and his colleagues, "since it is associated with positive long-term clinical outcomes."
Pegasys: Expanded Use
Pegasys was just approved this past May as a therapy for hepatitis B. It's been available as a hepatitis C treatment since late 2002.3 It's the only pegylated interferon available to treat both variations of HBV: HBeAg-positive and HBeAg-negative chronic hepatitis B—a mutant form of the virus that has demonstrated resistance to other therapies.4 It works in two ways: by slowing replication of HBV and also boosting the immune system's response to the virus.
Common side effects reported by the study participants included fever, fatigue, headache, muscle pain, hair loss, and anorexia, which is common with interferon use.5
The study's findings are similar to a Phase 3 trial published last year6 that found Pegasys was more effective at achieving long-term remission of hepatitis B compared to Epivir. In this trial, all of the patients were hepatitis B envelope antigen-negative. The study results supported Pegasys as first-line therapy for people with HBeAg-negative chronic HBV who have evidence of compensated liver disease, active viral replication, and liver inflammation.
Mixed Reaction
In an editorial accompanying the latest study,7 Anna Suk-Fong Lok, MD, a gastroenterologist at the University of Michigan Medical Center in Ann Arbor, says the current treatment options are disappointing, given the fact that they "suppress but do not eradicate HBV." Viral drug resistance is another complex problem, Lok writes, particularly with the use of nucleoside analogs such as Epivir or Hepsera (adefovir dipivoxil). While not all patients develop resistance, some can, experts say.
Still, Lok is optimistic about the wider availability of HBV medications: "Ten years ago, conventional interferon was the only approved treatment for chronic hepatitis B. Since then, three orally administered nucleoside or nucleotide analogs and a long-acting (pegylated) interferon have been approved in the United States. Patients with chronic hepatitis B now have more treatment options that have fewer side effects and are more easily administered."
1. Lau GK, Piratvisuth T, Luo KX et al. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med 2005 Jun 30;352(26):2682-95.
2. American Academy of Family Physicians. Hepatitis B Envelope Antigen and Hepatocellular Carcinoma. Available at: http://www.aafp.org/afp/20021101/tips/2.html. Accessed July 6, 2005.
3. U.S. Food and Drug Administration. Product Approval Information – Licensing Action. Available at: http://www.fda.gov/cder/biologics/products/pegihof120302.htm. Accessed July 6, 2005.
4. Manns MP. Current state of interferon therapy in the treatment of chronic hepatitis B. Semin Liver Dis 2002;22 Suppl 1:7-13.
5. Hepatitis Neighborhood. Interferons/Pegylated Interferon Side Effects. Available at: http://www.hepatitisneighborhood.com/content/
treatment_options/medication_side_effects_295.aspx. Accessed July 7, 2005.
6. Marcellin P, Lau GK, Bonino F et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2004 Sep 16;351(12):1206-17.
7. Lok AS. The maze of treatments for hepatitis B. N Engl J Med 2005 Jun 30;352(26):2743-6.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
