Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 18, 2017; 9(11): 551-561
Published online Apr 18, 2017. doi: 10.4254/wjh.v9.i11.551
Factors associated with success of telaprevir- and boceprevir-based triple therapy for hepatitis C virus infection
Kian Bichoupan, Neeta Tandon, Valerie Martel-Laferriere, Neal M Patel, David Sachs, Michel Ng, Emily A Schonfeld, Alexis Pappas, James Crismale, Alicia Stivala, Viktoriya Khaitova, Donald Gardenier, Michael Linderman, William Olson, Ponni V Perumalswami, Thomas D Schiano, Joseph A Odin, Lawrence U Liu, Douglas T Dieterich, Andrea D Branch
Kian Bichoupan, Neeta Tandon, Valerie Martel-Laferriere, Neal M Patel, David Sachs, Michel Ng, Emily A Schonfeld, Alexis Pappas, James Crismale, Alicia Stivala, Viktoriya Khaitova, Donald Gardenier, Michael Linderman, William Olson, Ponni V Perumalswami, Thomas D Schiano, Joseph A Odin, Lawrence U Liu, Douglas T Dieterich, Andrea D Branch, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, Icahn Medical Instititute, New York, NY 10029, United States
Neeta Tandon, William Olson, Janssen Pharmaceuticals Companies, Division of Janssen Scientific Affairs Inc., Titusville, NJ 08560, United States
David Sachs, Michael Linderman, Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Author contributions: Bichoupan K, Tandon N, Olson W and Branch AD designed the research; Bichoupan K and Martel-Laferriere V performed the research; Bichoupan K analyzed the data; Bichoupan K, Tandon N, Martel-Laferriere V, Patel NM, Sachs D, Ng M, Schonfeld EA, Pappas A, Crismale J, Stivala A, Khaitova V, Gardenier D, Linderman M, Olson W, Perumalswami PV, Schiano TD, Odin JA, Liu LU, Dieterich DT and Branch AD revised and edited the manuscript.
Supported by Janssen Scientific Affairs, LLC (partially) to Andrea D Branch to conduct the study; National Institute of Health (NIH), Nos. DK090317 and DA031095 (partially) to Andrea D Branch to conduct the study.
Institutional review board statement: The study was reviewed at approved by the Icahn School of Medicine at Mount Sinai Institutional Review Board.
Informed consent statement: Study participants did not provide informed consent prior to study enrollment as the Icahn School of Medicine at Mount Sinai Institutional Review Board provided a waiver of authorization to release deidentified patient data for research purposes.
Conflict-of-interest statement: Kian Bichoupan is a paid consultant for Gilead Sciences and Janssen Pharmaceuticals, Inc. Dr. Andrea D Branch is a paid consultant for Gilead Sciences and Janssen Pharmaceuticals, Inc. Dr. Douglas T Dieterich serves as a paid lecturer, consultant and is a member on scientific advisory boards of companies which either develop or assess medicines used for the treatment of viral hepatitis. These companies include Gilead Sciences, Abbvie, Achillion, Bristol-Myers Squibb, Merck, and Janssen Pharmaceuticals, Inc. Dr. Thomas D Schiano is a paid consultant for Salix, Merck, Gilead, BMS, Novartis and Janssen and received research support from Mass biologics, Gilead, Merck, Biotest and Genentech. Michel Ng is a paid member of AbbVie’s Speakers bureau. Viktoriya Khaitova is a paid member of a scientific advisory board for Abbvie, and Johnson & Johnson. Dr. Valerie Martel-Lafferiere, Dr. Emily A Schonfeld, Dr. James Crismale, Alicia Stivala, Donald Gardenier, Dr. David Sachs, Dr. Joseph A. Odin, Dr. Lawrence Liu, Dr. Neal M Patel, and Dr. Ponni V Perumalswami do not have any disclosures.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at kian.bichoupan@mssm.edu. Consent was not obtained but the presented data are anonymized and risk of identification is low.
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: Dr. Kian Bichoupan, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, Icahn Medical Instititute, 11th floor, Room 34, 1425 Madison Avenue, New York, NY 10029, United States. kian.bichoupan@mssm.edu
Telephone: +1-516-5671126 Fax: +1-212-8492574
Received: June 22, 2015
Peer-review started: June 23, 2015
First decision: September 21, 2015
Revised: February 10, 2017
Accepted: March 14, 2017
Article in press: March 17, 2017
Published online: April 18, 2017
Processing time: 316 Days and 2.8 Hours
Abstract
AIM

To evaluate new therapies for hepatitis C virus (HCV), data about real-world outcomes are needed.

METHODS

Outcomes of 223 patients with genotype 1 HCV who started telaprevir- or boceprevir-based triple therapy (May 2011-March 2012) at the Mount Sinai Medical Center were analyzed. Human immunodeficiency virus-positive patients and patients who received a liver transplant were excluded. Factors associated with sustained virological response (SVR24) and relapse were analyzed by univariable and multivariable logistic regression as well as classification and regression trees. Fast virological response (FVR) was defined as undetectable HCV RNA at week-4 (telaprevir) or week-8 (boceprevir).

RESULTS

The median age was 57 years, 18% were black, 44% had advanced fibrosis/cirrhosis (FIB-4 ≥ 3.25). Only 42% (94/223) of patients achieved SVR24 on an intention-to-treat basis. In a model that included platelets, SVR24 was associated with white race [odds ratio (OR) = 5.92, 95% confidence interval (CI): 2.34-14.96], HCV sub-genotype 1b (OR = 2.81, 95%CI: 1.45-5.44), platelet count (OR = 1.10, per x 104 cells/μL, 95%CI: 1.05-1.16), and IL28B CC genotype (OR = 3.54, 95%CI: 1.19-10.53). Platelet counts > 135 x 103/μL were the strongest predictor of SVR by classification and regression tree. Relapse occurred in 25% (27/104) of patients with an end-of-treatment response and was associated with non-FVR (OR = 4.77, 95%CI: 1.68-13.56), HCV sub-genotype 1a (OR = 5.20; 95%CI: 1.40-18.97), and FIB-4 ≥ 3.25 (OR = 2.77; 95%CI: 1.07-7.22).

CONCLUSION

The SVR rate was 42% with telaprevir- or boceprevir-based triple therapy in real-world practice. Low platelets and advanced fibrosis were associated with treatment failure and relapse.

Keywords: Sustained virologic response; Hepatitis C virus; Relapse; Telaprevir; Boceprevir; Triple-therapy; Classification and regression; Adverse event; Real-world

Core tip: A cohort of 223 hepatitis C virus (HCV)-infected patients at a tertiary referral center was analyzed. All patients were treated with telaprevir and boceprevir. Using both logistic regression and a machine learning techniques we identified baseline and on-treatment factors associated with sustained virologic response and relapse. We found that both low platelet count and advanced fibrosis or cirrhosis were associated with treatment failure. Information of the effectiveness of these protease inhibitors could be used to inform clinical trials of future HCV direct-acting antivirals.