Tuesday, August 11, 2015

A Study of Health-related Quality of Life - Interferon Plus Ribavirin to Interferon- and Ribavirin-free HCV Regimens

The Patient's Journey With Chronic Hepatitis C From Interferon Plus Ribavirin to Interferon- and Ribavirin-free Regimens

A Study of Health-related Quality of Life
How do interferon and ribavirin impact health-related quality of life during treatment for chronic hepatitis C, and are patients better off with different drug therapies?

August 10, 2015
Z. M. Younossi; M. Stepanova; F. Nader; B. Lam; S. Hunt
Aliment Pharmacol Ther. 2015;42(3):286-295. 

Article Source - Medscape

Discussion ONLY

Link To Full Article
This is the largest analysis of  Health-related Quality of Life (HRQL) in over 3400 CH-C patients who were treated with a variety of anti-HCV regimens in nine phase 3 clinical trials. In this study, we clearly demonstrated a significant improvement of HRQL scores with regimens which were free of IFN, and more recently, regimens which are also free of both IFN and RBV. This significant improvement is in contrast to the substantial decrement seen in HRQL with the previous standard of care for chronic hepatitis C which included interferon and ribavirin and was associated with substantial side effects.[19–21]

The results of this analysis also document that the physical aspects of HRQL in CH-C patients were primarily predicted by the presence of fatigue, depression, insomnia, and diabetes. Additionally, the strongest predictors of mental health aspects of HRQL were also depression, anxiety, and fatigue, all consistent with prior reports.[11–18] Although some of these factors may be related to the host, it is possible that some factors, such as fatigue, may be related to HCV viremia and could improve after viral eradication. Indeed, viral eradication 12 weeks after treatment cessation was observed together with improvement in a number of HRQL domain scores which was especially prominent for the vitality domain.

In multivariate analysis, we showed that receiving a regimen that contained both IFN and RBV was the strongest negative predictor of HRQL during treatment, while IFN- and RBV-free (LDV/SOF) was the only regimen independently associated with HRQL improvement during treatment. Furthermore, LDV/SOF remained the only independent predictor of HRQL improvement after achieving SVR-12. We also have shown that the negative effect of IFN does lessen with longer follow-up in patients who cleared HCV infection. In fact, this is the first study which demonstrates that by 24 weeks after treatment cessation, post-treatment HRQL improvement after virologic clearance is manifested regardless of the regimen. Nevertheless, it is still possible that patients who receive interferon may have longer lasting effect which can be picked up by more in-depth neuropsychiatric testing. These potential changes were not detectable by SF-36 instrument.

To the study limitations, we could not strictly assess the magnitude of the impact of SVR to HRQL after treatment cessation due to short follow-up and small number of non-responders. Furthermore, limiting assessment to 24 weeks post-treatment limited the potential long-term implications of viral clearance. Also, some important and difficult to treat HCV subpopulations, such as patients with renal failure, decompensated cirrhosis or liver transplants, were not enrolled. Furthermore, the original clinical trials used in this study were not designed to be comparable, so adjustments were made to account for the bias in the study cohort, thus, introducing uncertainty. Additionally, a number of socio-economic and clinical factors which may also affect HRQL, including but not limited to the level of education, income, residence, marital status, social support, the route of HCV transmission, duration of the infection, family history of major comorbidities, etc., were not available so could not be adjusted for. Finally, none of the original trials were pragmatic, i.e. conducted in real-life, routine practice conditions, while efficacy observed in explanatory clinical trials may not necessarily translate into similarly high effectiveness in real life so the degree of generalisability of our results remain unclear.

In conclusion, the use of the new IFN-free and RBV-free regimens results in substantial improvement in patients' HRQL scores during and after treatment. These HRQL data, when considered together with the excellent efficacy and safety profile of these regimens, provides a more comprehensive picture of the true impact these new treatments have on patients' lives.


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