Clinical Trials Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2019; 25(18): 2229-2239
Published online May 14, 2019. doi: 10.3748/wjg.v25.i18.2229
Ombitasvir/paritaprevir/ritonavir + dasabuvir +/- ribavirin in real world hepatitis C patients
Nicole Loo, Eric Lawitz, Naim Alkhouri, Jennifer Wells, Carmen Landaverde, Angie Coste, Rossalynn Salcido, Michael Scott, Fred Poordad
Nicole Loo, Eric Lawitz, Naim Alkhouri, Jennifer Wells, Carmen Landaverde, Angie Coste, Rossalynn Salcido, Michael Scott, Fred Poordad, Academic and Clinical Affairs, Texas Liver Institute, 607 Camden Street, San Antonio, TX 78215, United States
Author contributions: Poordad F and Lawitz E designed research; Loo N, Lawitz E, Alkhouri N, Wells J, Landaverde C, Coste A, Salcido R, Scott M and Poordad F performed research; Poordad F analyzed data and wrote paper.
Supported by: an investigator-initiated grant from AbbVie (B15-791).
Institutional review board statement: The study protocol was approved by the Integ Review Institutional Review Board.
Informed consent statement: All patients provided written informed consent.
Conflict-of-interest statement: Dr. Lawitz and Dr. Poordad report grants and personal fees from AbbVie during the conduct of the study; grants and personal fees from Gilead, grants and personal fees from Merck outside the submitted work; Dr. Alkhouri reports grants and personal fees from AbbVie during the conduct of the study; grants and personal fees from Gilead, grants from Merck outside the submitted work; Dr. Loo reports grants from AbbVie during the conduct of the study; personal fees from Gilead outside the submitted work; Ms. Coste, Dr. Landaverde, Ms. Salcido, Dr. Scott and Dr. Wells report grants from AbbVie during the conduct of the study.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article which selected by an in-house editor and fully peer-reviewed by external reviewers. It 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/
Corresponding author: Fred Poordad, MD, Professor, Academic and Clinical Affairs, Texas Liver Institute, 607 Camden Street, San Antonio, TX 78215, United States. poordad@txliver.com
Telephone: +1-210-2533426 Fax: +1-210-2276951
Received: February 3, 2019
Peer-review started: February 6, 2019
First decision: March 14, 2019
Revised: March 21, 2019
Accepted: April 10, 2019
Article in press: April 10, 2019
Published online: May 14, 2019
Processing time: 102 Days and 10.1 Hours
Abstract
BACKGROUND

The hepatitis C virus (HCV) NS5A inhibitor ABT-267 (ombitasvir, OBV), the HCV NS4/4A protease inhibitor ABT-450 (paritaprevir, PTV), the CYP3A inhibitor ritonavir (r) and the non-nucleoside NS5B polymerase inhibitor ABT-333 (dasabuvir, DSV) (OBV/PTV/r + DSV) with or without ribavirin (RBV) is a direct-acting antiviral regimen approved in the United States and other major countries for the treatment of HCV in genotype 1 (GT1) infected patients. Patients with HCV who are considered “hard-to-cure” have generally been excluded from registration trials due to rigorous study inclusion criteria, presence of comorbidities and previous treatment failures.

AIM

To investigate the efficacy of this regimen in HCV G1-infected patients historically excluded from clinical trials.

METHODS

Patients were ≥ 18 years old and chronically infected with HCV GT1 (GT1a, GT1b or GT1a/1b). Patients were treatment-naïve or previously failed a regimen including pegylated interferon/RBV +/- telaprevir, boceprevir, or simeprevir. One hundred patients were treated with the study drug regimen, which was administered for 12 or 24 wk +/- RBV according to GT1 subtype and presence/absence of cirrhosis. Patients were evaluated every 4 wk from treatment day 1 and at 4 and 12 wk after end-of-treatment.

RESULTS

Many of the patients studied had comorbidities (44.2% hypertensive, 33.7% obese, 20.2% cirrhotic) and 16% previously failed HCV treatment. Ninety-six patients completed study follow-up and 99% achieved 12-wk sustained virologic response. The majority (88.4%) of patients had undetectable HCV RNA by week 4. The most common adverse events were fatigue (12%), headache (10%), insomnia (9%) and diarrhea (8%); none led to treatment discontinuation. Physical and mental patient reported outcomes scores significantly improved after treatment. Almost all (98%) patients were treatment compliant.

CONCLUSION

In an all-comers HCV GT1 population, 12 or 24-wk of OBV/PTV/r + DSV +/- RBV is highly effective and tolerable and results in better mental and physical health following treatment.

Keywords: Hepatitis C; Ombitasvir; Paritaprevir; Ritonavir; Dasabuvir; Genotype 1

Core tip: The hepatitis C virus (HCV) NS5A inhibitor ABT-267 (ombitasvir, OBV), HCV NS4/4A protease inhibitor ABT-450 (paritaprevir, PTV), CYP3A inhibitor ritonavir (r) and non-nucleoside NS5B polymerase inhibitor ABT-333 (dasabuvir, DSV) (OBV/PTV/r + DSV) with or without ribavirin (RBV) is an approved direct-acting antiviral regimen less frequently studied in an all-comers population. This study included 96 all-comers; many had comorbidities (44.2% hypertensive, 33.7% obese, 20.2% cirrhotic) and 16% previously failed HCV treatment. In these patients, 12 or 24-wk of OBV/PTV/r + DSV +/- RBV was highly effective (99% sustained virologic response for 12 wk treatment), tolerable and resulted in better mental and physical health.