SUMMARY: People with hepatitis B "e" antigen (HBeAg) positive chronic hepatitis B virus (HBV) infection respond best to a regimen of pegylated interferon alfa-2b (PegIntron) administered at 1.5 mcg/kg/week for 48 weeks, compared with a lower dose and/or shorter duration, according to a Chinese study presented last week at the American Association for the Study of Liver Diseases "Liver Meeting" (AASLD 2010) this week in Boston.

By Liz Highleyman

Standard therapy for chronic hepatitis B consists of oral antiviral agents (nucleoside/nucleotide analogs) or pegylated interferon, and sometimes a combination thereof. In the U.S., only pegylated interferon alfa-2a (Pegasys) is approved for hepatitis B treatment, but clinicians may also prescribe pegylated interferon alfa-2b, which is approved for hepatitis C. The optimum regimen has not been determined, however.

In the present study, researchers assessed the safety and efficacy of 3 different pegylated interferon alfa-2b regimens. The analysis included 670 patients (mostly from China, but a few from Southeast Asia) with HBeAg positive chronic hepatitis B. They were hepatitis B surface antigen (HBsAg) positive for at least 6 months, had undetectable serum surface and "e" antibodies (anti-HBs and anti-HBe, respectively), and had HBV DNA viral load > 20,000 IU/mL.

Participants were randomly allocated (1:1:1) to receive the following pegylated interferon alfa-2b regimens:

	1.0 mcg/kg/week for 24 weeks (Arm A);
	1.5 mcg/kg/week for 24 weeks (Arm B);
	1.5 mcg/kg/week for 48 weeks (Arm C).

The investigators looked at efficacy outcomes including proportion of patients with HBeAg loss, HBe seroconversion, HBV DNA < 20,000 IU/mL, alanine aminotransferase (ALT) normalization, and combined response (HBe seroconversion + HBV DNA < 20,000 IU/mL + ALT normalization). These were assessed 24 weeks after the end of treatment. Safety and tolerability were also evaluated.

Results

	Pegylated interferon alfa-2b at 1.5 mcg/kg/week for 48 weeks was more effective than the lower-dose, shorter duration regimen of 1.0 mcg/kg/week for 24 weeks.
	There were no significant differences in any outcomes between the 1.5 mcg/kg/week for 24 weeks and 1.0 mcg/kg/week for 24 weeks regimens.
	1.5 mcg/kg/week for 48 weeks resulted in a larger proportion of patients with all favorable outcomes:
	HBeAg loss: 17.3% in Arm A, 18.1% in Arm B, and 31.3% in Arm C; HBe seroconversion: 16.9%, 16.3%, and 29.9%, respectively; HBV DNA < 20,000 IU/mL: 19.6%, 21.3%, and 33.5%, respectively; ALT normalization: 28.0%, 36.2%, and 46.0%, respectively; Combined response: 8.0%, 10.4%, and 20.1%, respectively.
	Similar proportions of patients reported adverse events in all arms (81%, 83%, and 88% in Arms A, B and C, respectively).
	Rates of serious adverse events were 4%, 5%, and 7%, respectively.
	The most frequently reported adverse events were fever, muscle aches, headache, fatigue, joint pain, dizziness, hair loss, weakness, chills, decreased appetite, nausea, and weight loss.

"For treatment of patients with HBeAg positive chronic hepatitis B, a regimen of [pegylated interferon alfa-2b] 1.5 mcg/kg/week for 48 weeks was more efficacious than 1.0 mcg/kg/week for 24 weeks," the investigators concluded. "The safety and tolerability profiles of all regimens were comparable."

Investigator affiliations: Beijing Ditan Hospital, Capital Medical University, Beijing, China; Department of Infectious Diseases, Southwest Hospital, Third Military Medical University of PLA, Chongqing, China; Department of Infectious Diseases, Union Hospital, Huazhong Science and Technology University, Wuhan, China; Department of Infectious Diseases, Nanfang Hospital, Nanfang University, Guangzhou, China; Medical Department, MSD China, Shanghai, China.

11/5/10

Reference
X Fan, Y Wang, D Luo, and others. A Head-to-Head Comparison of Peginterferon ?-2b Treatment Regimens in the Treatment of Chinese and South-East Asian Patients with HBeAg Positive Chronic Hepatitis B. 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2010). Boston, October 29-November 2, 2010. Abstract 133.