Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2015; 21(28): 8660-8669
Published online Jul 28, 2015. doi: 10.3748/wjg.v21.i28.8660
Boceprevir early-access for advanced-fibrosis/cirrhosis in Asia-pacific hepatitis C virus genotype 1 non-responders/relapsers
Wattana Sukeepaisarnjaroen, Tri Pham, Tewesak Tanwandee, Saroja Nazareth, Sam Galhenage, Lindsay Mollison, Leanne Totten, Alan Wigg, Rosalie Altus, Anton Colman, Brenda Morales, Sue Mason, Tracey Jones, Nadine Leembruggen, Vince Fragomelli, Cheryl Sendall, Richard Guan, Dede Sutedja, Soek Siam Tan, Yock Young Dan, Yin Mei Lee, Widjaja Luman, Eng Kiong Teo, Yin Min Than, Teerha Piratvisuth, Seng Gee Lim
Wattana Sukeepaisarnjaroen, Srinagarind Hospital, Chiangmai 40002, Khon Kaen, Thailand
Tri Pham, Cabramatta Practice, Sydney, NSW 2166, Australia
Tewesak Tanwandee, Siriraj Hospital, Bangkok, Bangkoknoi 10700, Thailand
Saroja Nazareth, Nadine Leembruggen, Royal Perth Hospital, Perth, Western Australia, WA 6000, Australia
Sam Galhenage, Lindsay Mollison, Leanne Totten, Fremantle Hospital, Fremantle, Western Australia, WA 6160, Australia
Alan Wigg, Rosalie Altus, Flinders Medical Centre, Adelaide, South Australia, SA 5042, Australia
Anton Colman, Royal Adelaide Hospital, Adelaide, South Australia, SA 5000, Australia
Brenda Morales, Austin Hospital, Melbourne, Victoria, VIC 3081, Australia
Sue Mason, Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia
Tracey Jones, John Hunter Hospital, New Lambton, NSW 2305, Australia
Vince Fragomelli, Nepean Hospital, Sydney, New South Wales, NSW 2305, Australia
Cheryl Sendall, Cairns Base Hospital, Cairns, Queensland, QLD 4870, Australia
Richard Guan, Widjaja Luman, Mount Elizabeth Medical Centre, Singapore 228510, Singapore
Dede Sutedja, Gleneagles Hospital, Singapore 258500, Singapore
Soek Siam Tan, Selayang Hospital, 68100 Batu Caves, Selangor, Malaysia
Yock Young Dan, Yin Mei Lee, Yin Min Than, Seng Gee Lim, National University Health System, Singapore 119228, Singapore
Yock Young Dan, Seng Gee Lim, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
Eng Kiong Teo, Changi General Hospital, Singapore 529889, Singapore
Teerha Piratvisuth, NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand
Author contributions: Sukeepaisarnjaroen W, Pham T, Tanwandee T, Nazareth S, Galhenage S, Mollison L, Totten L, Wigg A, Altus R, Colman A, Morales B, Mason S, Jones T, Leembruggen N, Fragomelli V, Sendall C, Guan R, Sutedja D, Tan S, Dan YY, Lee YM, Luman W, Teo EK and Than YM acquired the data, analyzed and interpreted the data, critically revised the paper and gave final approval to the manuscript. Piratvisuth T and Lim SG conceived and designed the study, acquired, analyzed and interpreted the data, drafted and critically revised the manuscript and gave final approval of submitted version of manuscript. All authors contributed to the manuscript.
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: Seng Gee Lim, MBBS, MD, FRCP, FRACP, FAMS, Director, Department of Gastroenterology and Hepatology, National University Health System, 1E Lower Kent Ridge Road, Singapore 119228, Singapore. mdclimsg@nus.edu.sg
Telephone: +65-67-724369 Fax: +65-67-724361
Received: September 10, 2014
Peer-review started: September 11, 2014
First decision: October 14, 2014
Revised: November 21, 2014
Accepted: January 8, 2015
Article in press: January 8, 2015
Published online: July 28, 2015
Processing time: 322 Days and 14.2 Hours
Abstract

AIM: To examined the efficacy and safety of treatment with boceprevir, PEGylated-interferon and ribavirin (PR) in hepatitis C virus genotype 1 (HCVGT1) PR treatment-failures in Asia.

METHODS: The Boceprevir Named-Patient Program provided boceprevir to HCVGT1 PR treatment-failures. Participating physicians were invited to contribute data from their patients: baseline characteristics, on-treatment responses, sustained virological response at week 12 (SVR12), and safety were collected and analysed. Multivariate analysis was performed to determine predictors of response.

RESULTS: 150 patients were enrolled from Australia, Malaysia, Singapore and Thailand (Asians = 86, Caucasians = 63). Overall SVR12 was 61% (Asians = 59.3%, Caucasians = 63.5%). SVR12 was higher in relapsers (78%) compared with non-responders (34%). On-treatment responses predicted SVR, with undetectable HCVRNA at week 4, 8 and 12 leading to SVR12s of 100%, 87%, and 82% respectively, and detectable HCVRNA at week 4, 8 and 12, leading to SVR12s of 58%, 22% and 6% respectively. Asian patients were similar to Caucasian patients with regards to on-treatment responses. Patients with cirrhosis (n = 69) also behaved in the same manner with regards to on-treatment responses. Those with the IL28B CC genotype (80%) had higher SVRs than those with the CT/TT (56%) genotype (P = 0.010). Multivariate analysis showed that TW8 and TW12 responses were independent predictors of SVR. Serious adverse events occurred in 18.6%: sepsis (2%), decompensation (2.7%) and blood transfusion (14%). Discontinuations occurred in 30.7%, with 18.6% fulfilling stopping rules.

CONCLUSION: Boceprevir can be used successfully in PR treatment failures with a SVR12 > 80% if they have good on-treatment responses; however, discontinuations occurred in 30% because of virological failure or adverse events.

Keywords: Chronic hepatitis C; Treatment failure; Rapid virological response; Lead-in; Null response; Partial response; Relapse; Cirrhosis; Response guided therapy

Core tip: This is the first report of boceprevir, PEGylated interferon and ribavirin in PEGylated interferon treatment failures in the Asia-Pacific and showed an overall sustained virological response at week 12 (SVR12) of 61%. Asians were compared with Caucasians and had similar SVR12 results: Asians 59.3% and Caucasians 63.5%. On-treatment responses at week 4, 8 and 12 predicted SVR12. Multivariate analysis showed that treatment week 8 and 12 were independent predictors of SVR12. Serious adverse events occurred in 18.6%, comprising sepsis (2%), decompensation (2.7%) and blood transfusion (14%). Discontinuations occurred in 30.7%.