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Interferon-β plus ribavirin for patients with hepatitis C virus genotype 1: a randomised pilot trial
  1. M Enomoto1,
  2. A Tamori1,
  3. N Kawada1,
  4. H Jomura1,
  5. S Nishiguchi2,
  6. T Saibara3,
  7. S Onishi3,
  8. S Mochida4,
  9. K Fujiwara4
  1. 1Department of Hepatology, Osaka City University Medical School, Osaka, Japan
  2. 2Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
  3. 3Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi, Japan
  4. 4Division of Gastroenterology and Hepatology, Internal Medicine, Saitama Medical School, Saitama, Japan
  1. Correspondence to:
    Dr S Nishiguchi
    Division of Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya, Hyogo 663-8501, Japan; nishiguc{at}hyo-med.ac.jp

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The rate of sustained eradication of hepatitis C virus (HCV) in response to a combination of interferon-α and ribavirin remains unsatisfactory in patients with genotype 1 infection.1 No effective alternative treatment is currently available for non-responders. Interferon-β is also a type I interferon commonly used to treat chronic HCV infection in Japan. A previous study showed that a 24 week course of therapy with interferon-β plus ribavirin resulted in sustained loss of HCV in three of nine patients with chronic hepatitis C.2 However, the efficacy and safety of interferon-β combined with ribavirin has yet to be fully evaluated.

We report the results of a randomised pilot trial comparing interferon-β plus ribavirin with interferon-α plus ribavirin in patients with HCV genotype 1 who poorly responded to interferon-α plus ribavirin. A total of 28 patients with HCV genotype 1 were given 6 MU of recombinant interferon-α2b (Schering-Plough, Kenilworth, New Jersey, USA) by intramuscular injection daily for four weeks. Twenty seven patients (16 men and 11 women; mean age 47 (±8) years) in whom HCV RNA was detected in serum on polymerase chain reaction at week 2 were included in this study and randomly assigned to receive one of two regimens from week 5. Fifteen patients continued to receive 6 MU interferon-α2b intramuscularly, given daily from week 5 to week 8, and three times weekly from week 9 to week 24 (interferon-α group). The other 12 patients were assigned to 6 MU natural interferon-β (Toray Industries Inc., Tokyo, Japan), given by intravenous injection daily from week 5 to week 8, and three times weekly from week 9 to week 24 (interferon-β group). Ribavirin (Schering-Plough) was concurrently administered at a daily dose of 600 mg to patients who weighed 60 kg or less and 800 mg to those who weighed more than 60 kg. At the time of this study, a 24 week course of interferon-α plus ribavirin was commonly used in Japan. The data were analysed according to intention to treat.

Baseline characteristics of the patients in the treatment groups were similar. At week 4 of therapy, when treatment was randomly assigned, the proportion of patients without detectable HCV RNA in serum did not differ between the interferon-α group and interferon-β groups (table 1). The proportion of patients without HCV RNA in serum was higher in the interferon-β group than in the interferon-α group at week 12, but did not differ between the groups at the end of treatment (week 24). However, 24 weeks later (week 48), the proportion of patients with a sustained virological response was significantly higher in the interferon-β group than in the interferon-α group. During treatment, neutralising antibodies to interferon were detected in two patients in the interferon-α group and in no patients in the interferon-β group. Leucocyte, neutrophil, and platelet counts and haemoglobin concentrations were similar in two groups. Therapy was discontinued because of serious adverse events (including depression) in three patients in the interferon-α group; all 12 patients in the interferon-β group completed 24 weeks of treatment. The dose of ribavirin was reduced because of anaemia in eight patients in the interferon-α group and in four in the interferon-β group.

Table 1

 Proportions of patients without detectable hepatitis C virus RNA in serum

We enrolled patients who did not have a favourable early response to treatment with interferon-α and ribavirin. Antibodies to interferon, which sometimes develop in patients given recombinant interferon-α, can cause resistance to therapy. Both interferon-α and -β bind to a common type I interferon receptor but utilise different regions of the receptor subunits for specific signalling pathways,3 potentially leading to distinct biological responses. An oligonucleotide array study has shown that some interferon stimulated genes are preferentially induced by interferon-β, but not by interferon-α.4 We thus believe that interferon-β might be beneficial for some patients who are resistant to interferon-α. A large randomised trial of peginterferon-α plus ribavirin versus interferon-β plus ribavirin for 48 weeks is being conducted in patients with HCV genotype 1 who do not have a virological response5 to 12 weeks of treatment with peginterferon-α and ribavirin.

In summary, a combination of interferon-β and ribavirin produced a significantly better sustained virological response than a combination of interferon-α and ribavirin in patients with HCV genotype 1 who were resistant to interferon-α plus ribavirin. Although the overall safety profiles of the two regimens were similar, the rates of treatment discontinuation and of reduction in the dose of ribavirin were lower in patients receiving interferon-β and ribavirin than in those receiving interferon-α and ribavirin.

Acknowledgments

Grant support was received from Ministry of Health, Labour, and Welfare, Japan.

References

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Footnotes

  • Conflict of interest: None declared.

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