Shorter durations and lower doses of peginterferon alfa-2a... : Hepatology (original) (raw)

Viral Hepatitis

Shorter durations and lower doses of peginterferon alfa-2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C

Liaw, Y.-F.1,*; Jia, J.-D.2; Chan, H. L.Y.3; Han, K. H.4; Tanwandee, T.5; Chuang, W. L.6; Tan, D. M.7; Chen, X. Y.8; Gane, E.9; Piratvisuth, T.10; Chen, L.11; Xie, Q.12; Sung, J. J.Y.3; Wat, C.13; Bernaards, C.14; Cui, Y.15; Marcellin, P.16

1_Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan_

2_Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China_

3_Department of Medicine and Therapeutics and Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong SAR, China_

4_Department of Internal Medicine, Yonsei University College of Medicine, Yonsei, Korea_

5_Division of Gastroenterology, Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand_

6_Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan_

7_Department of Infectious Diseases, Xiangya Hospital, Central South University, Xiangya, China_

8_Beijing Youan Hospital, Capital Medical University, Beijing, China_

9_Liver Unit, Auckland City Hospital, Auckland, New Zealand_

10_NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand_

11_Shanghai Public Health Clinical Center, Fudan University, Shanghai, China_

12_Department of Infectious Diseases, Ruijin Hospital, Shanghai, China_

13_Roche Products Ltd., Welwyn Garden City, UK_

14_Department of Biostatistics, Genentech Inc., South San Francisco, CA, USA_

15_Roche Product Development in Asia Pacific, Shanghai Roche Pharmaceuticals Ltd., China_

16_Service d'Hepatologie and Centre de Recherches Biologiques Beaujon (Inserm CRB3), University of Paris, Clichy, France_

*Address reprint requests to: Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan, 199, Tung Hwa North Road, Taipei 105, Taiwan

Email: [email protected]

Published online 4 October 2011 in Wiley Online Library(wileyonlinelibrary.com).

Potential conflict of interest: Nothing to report.

The study was financed and run by F. Hoffmann-La Roche, Basel, Switzerland

Fax: 886-3-3282824

Abstract

As there is currently a lack of consensus on the most appropriate dose and duration of peginterferon alfa-2a (PEG-IFNα-2a) therapy in hepatitis B e antigen (HBeAg)-positive patients, the efficacy and safety of either 24 or 48 weeks' duration and 90 μg/week or 180 μg/week doses were compared. HBeAg-positive patients (n = 544; 34% genotype B, 51% genotype C) were randomized to receive PEG-IFNα-2a (2 × 2 factorial design) for 24 or 48 weeks and at 90 μg/week or 180 μg/week and included in the per-protocol population. The primary efficacy endpoint of the noninferiority study was HBeAg seroconversion 6 months posttreatment. The prespecified odds ratio (OR) noninferiority margin was 1.88 with a one-sided significance level of 0.025. The highest rates of HBeAg seroconversion 6 months posttreatment were in the 180/48 arm (36.2% versus 14.1%-25.8% in the other arms). When the dose and duration arms were pooled, the OR for noninferiority of 24 weeks versus 48 weeks was 2.17 (95% confidence interval [CI] 1.43, 3.31; P = 0.749) and for 90 μg versus 180 μg was 1.79 (95% CI 1.18, 2.72; P = 0.410). As the upper limit of the 95% CI of the ORs were >1.88, 24 weeks were inferior to 48 weeks and 90 μg/week was inferior to 180 μg/week. The highest rates of response in the 180/48 arm were achieved by patients with HBsAg <1,500 IU/mL at Week 12 (58%) or Week 24 (57%), whereas patients with HBsAg >20,000 IU/mL did not respond. Adverse events were typical of those associated with PEG-IFNα-2a. Conclusion: Compared with lower doses and shorter durations, the licensed PEG-IFNα-2a treatment regimen (180μg/48 weeks) was the most efficacious and beneficial for HBeAg-positive patients predominantly infected with hepatitis B virus genotypes B or C. (Hepatology 2011;)