Friday, February 17, 2017

Superiority of Interferon-Free Regimens for Chronic Hepatitis C: The Effect on Health-Related Quality of Life and Work Productivity

Superiority of Interferon-Free Regimens for Chronic Hepatitis C: The Effect on Health-Related Quality of Life and Work Productivity

Younossi, Zobair M. MD, MPH; Stepanova, Maria PhD; Esteban, Rafael MD; Jacobson, Ira MD; Zeuzem, Stefan MD; Sulkowski, Mark MD; Henry, Linda PhD; Nader, Fatema MS; Cable, Rebecca BS; Afendy, Mariam BS; Hunt, Sharon MBA

Section Editor(s): Janczewska., Ewa
February 2017 - Volume 96 - Issue 7 - p e5914
doi: 10.1097/MD.0000000000005914
Research Article: Observational Study

1 Introduction
The new direct-acting antiviral agents (DAAs) for treatment of hepatitis C virus (HCV) have revolutionized HCV treatment with high sustained viral response (SVR) rates and superior patient-reported outcomes (PROs).[1–12] Although new interferon (IFN)-free and ribavirin (RBV)-free regimens are currently being developed, both IFN and RBV remain a part of certain regimens.[1–4]
Previous studies have shown that treatment-naïve HCV patients treated with RBV and IFN experience a significant PRO impairment.[13,14] In particular, the use of IFN causes substantial side effects, including debilitating ones such as severe depression, which, in turn, affect patients’ ability to sustain treatment long enough to obtain a cure whether through medical discontinuation or through patients’ nonadherence. The use of RBV also has been shown to decrease PROs during treatment. However, the PRO data in patients who are retreated after having experienced another course of treatment have not been reported. Therefore, the aim of this study was to evaluate PROs during treatment with and without the use of IFN in patients who participated in a prior study of an IFN-containing or an IFN-free DAA-based regimen and has not achieved SVR.

Discussion Only
The purpose of this study was to investigate the impact of alternative hepatitis C treatment regimens on patient-reported outcomes (PROs).[In this study, we have found that patients who were treated with a regimen containing IFN experienced a substantial decrease in their PRO scores during and even shortly after treatment. According to the multivariate analysis, the use of IFN was also found to be an independent predictor of substantial PRO impairment, and that association was observed up to 12 weeks after treatment discontinuation. Although PROs were also impacted by IFN-free regimens that contained RBV, the magnitude of such impact is much smaller. These data are consistent with previously published PRO data.[2–10,21–23]

Across both IFN-free and IFN-containing treatment arms, PRO domains that were most affected by the treatment were the domains primarily associated with daily functioning and physical activity. Thus, it is imperative for healthcare practitioners to assist patients in dealing with these areas by identifying strategies patients can pursue to stay active and social.

A number of previous studies of the use of IFN for treatment of chronic HCV infection have shown the negative effect of IFN on PROs.[13,14] In this study, we have shown that the impact of IFN-containing and IFN-free RBV-containing regimens on PROs of patients who are retreated is similar to those who have never been treated or have been treated with and IFN-free regimen only. In fact, experience with previous IFN-based treatment does not seem to predispose patients for better or worse experience during another course of treatment. Although HCV patients who were treatment-experienced with IFN had higher baseline PRO scores, most of these were likely due to previously applied strict treatment eligibility criteria.
A major limitation of this study is related to the original clinical trial design, which lacks both randomization and blinding. We, however, believe that the bias caused by this could be adequately accounted for by multivariate analysis.

In conclusion, treatment-experienced patients who were retreated with an IFN-containing regimen experienced significantly more impairment of their PROs in comparison to patients who were treated with an IFN-free regimen regardless of duration. However, it is important to note that, albeit accompanied by an unfavorable patients’ well-being profile, the IFN-containing regimen was still associated with a higher chance of SVR, especially in patients with HCV genotype 3. These 2 outcomes represent a trade-off that patients who have failed a DAA-based regimen may face, although the use of IFN, hopefully, will be revisited once new DAAs come to market and provide this cohort of patients with more treatment options.

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