Abstract
Background
Triple therapy with telaprevir (TVR), pegylated interferon and ribavirin has improved antiviral efficacy in patients with chronic hepatitis C (CH-C). However, the severe adverse effects caused by TVR are important to resolve. In this prospective, randomized, multicenter, open-label study, the antiviral efficacy and safety in the reduced administration of TVR were examined.
Methods
A total of 81 CH-C Japanese patients with HCV genotype 1 were randomized into two regimens of TVR 2250 mg (TVR-2250) or 1500 mg (TVR-1500) and treated with triple therapy for 24 weeks.
Results
The mean HCV RNA at start, 2 and 4 weeks of treatment were 6.69 ± 0.70, 1.05 ± 0.74, 0.22 ± 0.48 log10 IU/ml in the TVR-2250 group and 6.70 ± 0.62, 1.02 ± 0.62, 0.13 ± 0.41 log10 IU/ml in the TVR-1500 group. The SVR rates were 85 % in both groups (35/41 and 34/40, respectively). There were no patients with viral breakthrough in either group. As for adverse effects, rash more than moderate and severe anemia with <8.5 g/dl of hemoglobin were higher in the TVR-2250 group than in the TVR-1500 group (p = 0.046, p < 0.001, respectively). The increase in serum creatinine levels and decrease in estimated glomerular filtration rates were higher in the TVR-2250 group than in the TVR-1500 group.
Conclusions
The lower dose of TVR (1500 mg/day) can result in similar SVR rates and lower treatment-related adverse effects compared to the higher dose of TVR (2250 mg/day) in triple therapy (UMIN: 000007313, 000007330).
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Abbreviations
- HCV:
-
Hepatitis C virus
- IFN:
-
Interferon
- Peg-IFN:
-
Pegylated interferon
- RBV:
-
Ribavirin
- PI:
-
Protease inhibitor
- TVR:
-
Telaprevir
- SVR:
-
Sustained virologic response
- EOT:
-
End of treatment
- HCC:
-
Hepatocellular carcinoma
- CH-C:
-
Chronic hepatitis C
- Hb:
-
Hemoglobin
- WBC:
-
White blood cell
- RVR:
-
Rapid virologic response
- c-EVR:
-
Complete early virologic response
- ETR:
-
End of treatment response
- SMV:
-
Simeprevir
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Acknowledgments
Other institutions and participants in the Osaka Liver Forum are the following: National Hospital Organization Minami Wakayama Medical Center, M Kato; Osaka General Medical Center, A Inoue; Kinki Central Hospital of Mutual Aid Association of Public School Teachers, E Hayashi; Osaka Medical Center for Cancer and Cardiovascular Diseases, K Katayama; National Hospital Organization Osaka Minami Medical Center, T Hijioka; Osaka Koseinenkin Hospital, Y Ito; Yao Municipal Hospital, H Fukui; National Hospital Organization Osaka National Hospital, E Mita; Kansai Rousai Hospital, H Hagiwara; Higashiosaka City Central Hospital, S Iio,; Toyonaka Municipal Hospital, M Inada; Itami City Hospital, Y Saji; Otemae Hospital, Y Doi; Suita Municipal Hospital, T Nagase; Ashiya Municipal Hospital, A Takeda; Nishinomiya Municipal Central Hospital, H Ogawa; Kaizuka City Hospital, Y Yamada; Izumiotsu Municipal Hospital, S Yamagata; Osaka Kaisei Hospital, N Imaizumi; Kano General Hospital, S Kubota; Saso Hospital, M Nishiuchi; and Meiwa Hospital, Y Hayakawa.
This work was supported by a Grant-in-Aid for Research on Hepatitis and BSE from the Ministry of Health Labour and Welfare of Japan and a Scientific Research from the Ministry of Education, Science, and Culture of Japan.
Conflict of interest
Professor Tetsuo Takehara received scholarship funds from Merck Sharp & Dohme K.K. Co., Ltd. and Chugai Pharmaceutical Co., Ltd. Other authors declare thath they have no conflict of interest.
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Oze, T., Hiramatsu, N., Yakushijin, T. et al. The prospective randomized study on telaprevir at 1500 or 2250 mg with pegylated interferon plus ribavirin in Japanese patients with HCV genotype 1. J Gastroenterol 50, 313–322 (2015). https://doi.org/10.1007/s00535-014-0965-8
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DOI: https://doi.org/10.1007/s00535-014-0965-8