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Safety and effectiveness of daclatasvir and asunaprevir dual therapy in patients with genotype 1 chronic hepatitis C: results from postmarketing surveillance in Japan

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Abstract

Background

Safety and effectiveness of daclatasvir (DCV)/asunaprevir (ASV) dual therapy were demonstrated in Japanese patients with chronic hepatitis C (CHC) genotype (GT) 1b in phase III studies. This postmarketing surveillance (PMS) was conducted to assess the safety and effectiveness of DCV/ASV in Japanese patients with GT-1 CHC treated in routine clinical practice.

Methods

This PMS was conducted between September 2014 and February 2017 at 261 centers in Japan. Patients with GT-1 CHC with or without compensated cirrhosis starting DCV and ASV dual therapy were observed from treatment initiation until 24 weeks after completing treatment. Safety and effectiveness assessments included incidence of adverse drug reactions (ADRs) and sustained viral response (SVR) rates at 24 weeks (SVR24).

Results

Of 2820 patients (median age, 71.0 years; ≥ 65 years, 73.1%; female, 56.1%; with compensated cirrhosis, 39.1%) in the safety population, 726 (25.7%) experienced 1063 ADRs and 47 (1.7%) experienced 55 serious ADRs. Overall, 532 hepatic ADRs were reported; most hepatic ADRs occurred between > 4 and ≤ 12 weeks after treatment initiation. Subgroup analysis showed a higher incidence of ADRs in female, elderly, underweight, and renal function-impaired patients. SVR24 and SVR at 12 weeks (SVR12) were 87.3% (2216/2538) and 88.4% (2284/2584), respectively. Patients without (SVR12, 89.1%; SVR24, 87.9%) and with (SVR12, 87.3%; SVR24, 86.3%) compensated cirrhosis had similar SVR rates.

Conclusion

Results from this large PMS indicate that DCV and ASV dual therapy is generally well tolerated and effective in routine clinical practice in Japanese patients with GT-1 CHC with or without compensated cirrhosis.

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Acknowledgements

The authors thank all the medical institutions and physicians who participated in this surveillance for their cooperation. This surveillance was sponsored by Bristol-Myers Squibb (BMS) K.K. The authors thank Hiroki Ishikawa, BMS K.K., for contributions to the scientific review. Medical writing assistance was provided by Deepali Garg, MBBS, PGDHA, and Maribeth Bogush, PhD, of Cactus Communications and was funded by BMS K.K.

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Authors and Affiliations

  1. Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan

    Fumitaka Suzuki

  2. Bristol-Myers Squibb K.K, 6-5-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo, 163-1328, Japan

    Naoya Hatanaka, Etsuya Bando, Koji Nakamura & Akira Komoto

Authors
  1. Fumitaka Suzuki
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  2. Naoya Hatanaka
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  3. Etsuya Bando
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  4. Koji Nakamura
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  5. Akira Komoto
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Corresponding author

Correspondence to Fumitaka Suzuki.

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Conflict of interest

Fumitaka Suzuki has received personal fees from Abbott Japan, AbbVie, ASKA Pharmaceutical, BMS K.K., Chugai Pharmaceutical, Gilead Sciences, GlaxoSmithKline, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka Pharmaceutical, Roche Diagnostics, and Sumitomo Dainippon Pharma. Naoya Hatanaka, Etsuya Bando, Koji Nakamura, and Akira Komoto are employees of BMS K.K.

Ethical approval

This postmarketing surveillance (PMS) was conducted in accordance with Good Postmarketing Surveillance Practices (GPSP) as per the Japanese Pharmaceutical Affairs Law. Under GPSP regulations, Institutional Review Board approval and written informed consent are not required. This PMS is registered at ClinicalTrials.gov (NCT02250001).

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Suzuki, F., Hatanaka, N., Bando, E. et al. Safety and effectiveness of daclatasvir and asunaprevir dual therapy in patients with genotype 1 chronic hepatitis C: results from postmarketing surveillance in Japan. Hepatol Int 12, 244–253 (2018). https://doi.org/10.1007/s12072-018-9872-z

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  • DOI: https://doi.org/10.1007/s12072-018-9872-z

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