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
ARTICLE HIGHLIGHTS
Research background

The hepatitis C virus (HCV) is a prevalent virus that, if left untreated, leads to chronic liver disease and, ultimately, death. The new era of direct acting antiviral (DAA) treatment regimens has the potential to cure the virus [i.e., achieve sustained virologic response (SVR)] in the majority of patients. The HCV NS5A inhibitor ombitasvir (OBV), HCV NS4/4A protease inhibitor paritaprevir (PTV), the CYP3A inhibitor ritonavir and the non-nucleoside NS5B polymerase inhibitor dasabuvir (DSV) (OBV/PTV/r + DSV) with or without ribavirin (RBV) is a DAA regimen that achieves SVR rates as high as 99% in HCV genotype 1 (GT1) patients in controlled clinical studies. However, there are patients who are considered “hard to cure” that are traditionally excluded from registration trials due to rigorous study inclusion criteria, presence of comorbidities and previous treatment failures. This phase 4, open label study evaluated the safety and efficacy of OBV/PTV/r + DSV +/- RBV in a real-world clinical setting in patients who have historically been excluded from clinical trials. This study is completed.

Research motivation

Controlled clinical studies demonstrate 99% SVR rates in patients with HCV GT1, however, many patients in these studies do not meet the inclusion criteria for these studies. In a real world population of HCV patients, many have comorbidities or history of previous HCV treatment failures. We sought to examine the efficacy and safety of OBV/PTV/r + DSV +/- RBV in real world HCV patients who are generally underrepresented in clinical trials. This study also examined patient quality of life, dosing adherence and whether resistance-associated substitutions (RASs) impact achievement of SVR, which are all real world issues encountered in HCV patients. The results of this study will determine if controlled clinical trial results can be expected in everyday HCV patients seen in clinical practice.

Research objectives

The primary objective of this study was to examine the efficacy and safety of OBV/PTV/r + DSV +/- RBV in real world HCV patients generally underrepresented in clinical trials. This study found that this treatment regimen was highly effective and no adverse events were considered serious; these results are comparable to those seen in controlled clinical trials with this treatment regimen. Therefore, including patients with comorbidities or a history of previous HCV treatment(s) did not affect the results. According to this one study, the results demonstrated in controlled clinical trials involving OBV/PTV/r + DSV +/- RBV can be applied to everyday HCV patients seen in clinical practice.

Research 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.

Research 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.

Research conclusions

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.

Research perspectives

Results of he approved use of the OBV/PTV/r + DSV +/- RBV regimen in HCV GT1 patients in clinical practice can potential mirror results obtained in controlled clinical trials. The availability of real world data on approved HCV treatment regimens is extremely useful in clinical practice. Newer DAA regimens with shorter treatment durations have been recently approved. These regimens should also be evaluated in the real world population of HCV patients. Future clinical studies need to evaluate the efficacy and safety of these newer DAA regimens in real world patients. Patients with comorbidities and those who have had previous HCV treatment failures should be included in these studies. In addition, secondary measures should include physical and mental outcomes, the affects of RASs and adherence to the newer regimens.