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Telbivudine in combination with adefovir versus adefovir monotherapy in HBeAg-positive, lamivudine-resistant chronic hepatitis B

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Abstract

Purpose

Lamivudine (LAM) resistance is common on lamivudine monotherapy for chronic hepatitis B. This study examined the safety and efficacy of telbivudine (LDT) given with adefovir (ADV) versus ADV monotherapy in patients with chronic, lamivudine-resistant HBV infection.

Methods

An open-label, 96 week study with planned recruitment of 150 HBeAg-positive, lamivudine-experienced Asian patients with a confirmed YMDD resistance mutation, randomized 1:1 to receive ADV alone or with LDT. The study was terminated early due to difficulty in enrolling monotherapy patients. At termination, 42 patients had received study medication for 8–61 weeks. Due to incomplete enrolment, summary statistics only were prepared, without significance testing.

Results

A total of 42 patients underwent rescue therapy (switch to ADV or LDT + ADV; n = 21 per group). Median treatment duration was 48 weeks in both groups. HBV DNA changes from baseline were greater in the LDT + ADV arm at all time points (Week 48: −7.4 log10 vs. −4.9 log10 copies/ml), and serum DNA was undetectable (<300 copies/mL) at week 48 in 38.5% (5/13) on LDT + ADV versus 0% (0/9) on ADV monotherapy Two patients (9.6%) on ADV monotherapy experienced virologic breakthrough without evidence of ADV resistance, but none on LDT + ADV; and no confirmed ADV resistance was observed in any on-treatment sample. HBeAg loss occurred in three patients on LDT + ADV and one patient on ADV monotherapy through week 48. Safety profiles were similar between the arms.

Conclusion

LDT + ADV combination treatment showed better outcomes against lamivudine resistant HBV than ADV alone, with a similar safety profile.

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Acknowledgements

The authors would like to thank the patients, investigators and study centres for their participation. This manuscript was supported by Novartis Pharma AG, with editorial support by Mechthild Jung, Ph.D. (Novartis Pharma AG) and Nick Fitch, Ph.D. (Articulate Science, London, UK). The authors would also like to thank Delft Diagnostic Laboratory, The Netherlands, for performing the HBV DNA sequencing and resistance analyses described herein.

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Authors and Affiliations

  1. Department of Internal Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seoul, South Korea

    Sang-Hoon Ahn

  2. The Kyungpook National University Hospital, Daegu, Korea

    Young-Oh Kweon

  3. Department of Medicine/Gastroenterology, Samsung Medical Centre, Seoul, Korea

    Seung-Woon Paik

  4. Division of Gastroenterology, Hanyang University Guri Hospital, Gyeonggi-do, Suwon, Korea

    Joo-Hyun Sohn

  5. Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

    Kwan-Sik Lee

  6. Hallym University Sacred Heart Hospital, Chuncheon, Korea

    Dong Joon Kim

  7. NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand

    Teerha Piratvisuth

  8. Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong

    Man Fung Yuen

  9. Phramongkutklao Hospital, Bangkok, Thailand

    Anuchit Chutaputti

  10. Tri-Service General Hospital, Taipei, Taiwan, R.O.C

    You-Chen Chao

  11. Novartis Pharma AG, Basel, Switzerland

    Aldo Trylesinski & Claudio Avila

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  1. Sang-Hoon Ahn
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Correspondence to Sang-Hoon Ahn.

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Ahn, SH., Kweon, YO., Paik, SW. et al. Telbivudine in combination with adefovir versus adefovir monotherapy in HBeAg-positive, lamivudine-resistant chronic hepatitis B. Hepatol Int 6, 696–706 (2012). https://doi.org/10.1007/s12072-011-9314-7

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