Retrospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Feb 18, 2017; 9(5): 252-262
Published online Feb 18, 2017. doi: 10.4254/wjh.v9.i5.252
Efficacy and safety of telaprevir- and simeprevir-based triple therapies for older patients with chronic hepatitis C
Satoshi Yamagiwa, Toru Ishikawa, Nobuo Waguri, Soichi Sugitani, Hiroto Wakabayashi, Shogo Ohkoshi, Takashi Tsukishiro, Toru Takahashi, Toshiaki Watanabe, Shuji Terai
Satoshi Yamagiwa, Shuji Terai, Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
Toru Ishikawa, Department of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata 950-1104, Japan
Nobuo Waguri, Department of Gastroenterology and Hepatology, Niigata City General Hospital, Niigata 950-1197, Japan
Soichi Sugitani, Department of Gastroenterology and Hepatology, Tachikawa General Hospital, Nagaoka 940-8621, Japan
Hiroto Wakabayashi, Department of Gastroenterology and Hepatology, Takeda General Hospital, Aizuwakamatsu 965-8585, Japan
Shogo Ohkoshi, Department of Internal Medicine, Nippon Dental University Medical Hospital, Niigata 951-8580, Japan
Takashi Tsukishiro, Department of Internal Medicine, Itoigawa General Hospital, Itoigawa 941-8502, Japan
Toru Takahashi, Department of Internal Medicine, Uonuma Hospital, Ojiya 947-0028, Japan
Toshiaki Watanabe, Watanabe Clinic, Sanjyo 955-0845, Japan
Author contributions: Yamagiwa S, Ishikawa T, Waguri N and Terai S contributed to study conception and design; Yamagiwa S, Sugitani S, Wakabayashi H, Ohkoshi S, Tsukishiro T, Takahashi T and Watanabe T contributed to data acquisition, data analysis and interpretation; Yamagiwa S and Terai S contributed to drafting the article; all authors contributed to making critical revisions related to important intellectual content of the manuscript; all authors contributed to final approval of the version of the article to be published.
Supported by Grants-in-Aid for Scientific Research (C) (to Yamagiwa S) from Japan Society for the Promotion of Science (JSPS), No. 15K08991.
Institutional review board statement: The study was reviewed and approved by Niigata University Medical and Dental Hospital Institutional Review Board.
Informed consent statement: Written informed consent under institutional review board-approved protocols (approval no. 1474) at Niigata University Medical and Dental Hospital was appropriately obtained from all the individuals enrolled in the study.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Satoshi Yamagiwa, MD, PhD, Associate Professor, Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan. syamagi@med.niigata-u.ac.jp
Telephone: +81-25-2272207 Fax: +81-25-2270776
Received: August 22, 2016
Peer-review started: August 24, 2016
First decision: September 27, 2016
Revised: December 29, 2016
Accepted: January 11, 2017
Article in press: January 14, 2017
Published online: February 18, 2017
Processing time: 178 Days and 14.4 Hours
Abstract
AIM

To evaluate and compare the efficacy and safety of telaprevir (TVR)-and simeprevir (SMV)-based triple therapies in elderly patients, specifically patients aged 66 years or older.

METHODS

The present study enrolled 112 and 76 Japanese patients with chronic hepatitis C virus genotype 1b infection who were treated with a 12-wk TVR-based or SMV-based triple therapy, respectively, followed by a dual therapy that included pegylated interferon α and ribavirin (RBV) for 12 wk. The patients were categorized into two groups according to age as follows: A younger group of patients aged ≤ 65 years old and an older group of patients aged > 65 years old. Among the patients treated with TVR-based triple therapy, 34 patients were included in the older group. The median ages were 56 years (range: 28-65 years) in the younger group and 69 years (range: 66-81 years) in the older group. Among the patients treated with SMV-based triple therapy, 39 patients were included in the older group. The median ages were 59 years (range: 36-65 years) in the younger group and 71 years (range: 66-86 years) in the older group. The clinical, biochemical and virological data were analyzed before and during treatment.

RESULTS

Among the patients treated with the TVR-based triple therapy, no significant difference in the sustained virological response (SVR) was found between the younger (80.8%) and older (88.2%) groups. The SVR rates for patients with the interleukin 28B (IL28B) (rs8099917) TG/GG-genotypes (73.9% and 60.0% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype (86.3% and 92.9%, respectively). The cumulative exposure to RBV for the entire 24-wk treatment period (as a percentage of the target dose) was significantly higher in the younger group than in the older group (91.7% vs 66.7%, respectively, P < 0.01), but the cumulative exposure to TVR was not significantly different between the younger and older groups (91.6% vs 81.9%, respectively). A multivariate analysis identified the TT-genotype of IL28B (OR = 8.160; 95%CI: 1.593-41.804, P = 0.012) and the adherence of RBV (> 60%) (OR = 11.052; 95%CI: 1.160-105.273, P = 0.037) as independent factors associated with the SVR. Adverse events resulted in discontinuation of the treatment in 11.3% and 14.7% of the younger and older groups, respectively. Among the patients treated with the SMV-based triple therapy, no significant difference in the SVR rare was found between the younger (81.1%) and older (82.1%) groups. The SVR rates for patients with the IL28B TG/GG-genotypes (77.8% and 64.7% in the younger and older groups, respectively) were significantly lower than for patients with the IL28B TT-genotype (88.2% and 100%, respectively). A multivariate analysis identified the TT-genotype of IL28B as an independent factor associated with the SVR (OR = 9.677; 95%CI: 1.114-84.087, P = 0.040). Adverse events resulted in discontinuation of the treatment in 7.0% and 14.3% of patients in the younger and older groups, respectively.

CONCLUSION

Both TVR- and SMV-based triple therapies can be successfully used to treat patients aged 66 years or older with genotype 1b chronic hepatitis C. Genotyping of the IL28B indicates a potential to achieve SVR in these difficult-to-treat elderly patients.

Keywords: Telaprevir; Aged patients; Hepatitis C virus genotype 1b; Interleukin 28B; Simeprevir

Core tip: We evaluated the efficacy and safety of telaprevir (TVR)-and simeprevir (SMV)-based triple therapies for elderly patients with chronic hepatitis C, especially patients aged 66 years or older, in a real-world clinical setting. In both the TVR and SMV groups, no significant differences in the SVR and adverse events resulting in treatment discontinuation were found between the younger (aged ≤ 65) and older (aged > 65) patients. Both the TVR- and SMV-based triple therapies can be successfully used to treat patients aged 66 years or older with chronic hepatitis C virus genotype 1b infection. Genotyping of the interleukin-28B indicates a potential to achieve SVR in these difficult-to-treat elderly patients.