Outcomes improved during Hepatitis C treatment
Posted on April 7, 2015
An interferon-free and ribavirin-free anti-HCV regimen is shown to improve patient-reported outcomes during treatment
Chronic HCV infection causes a tremendous clinical and economic burden to society. Patient-reported outcomes (PROs) such as health-related quality of life (HRQL) and work productivity are negatively impacted by HCV-related liver disease (cirrhosis, HCC, and liver-related deaths) and HCV-related extrahepatic manifestations such as mixed type 2 cryoglobulinemia, fatigue, arthritis, porphyria cutanea tarda, insulin resistance and type 2 diabetes. Sustained eradication of HCV (sustained virologic response, or SVR) has been shown to improve patients’ survival, PRO scores, and reduces the risk of liver complications and the HCV-related economic burden. However, the interferon (IFN)-containing regimens and ribavirin (RBV) traditionally used to treat HCV have been shown to negatively impact PROs during treatment, which negatively affects patients’ experience and treatment adherence.
IFN-free and RBV-free chronic hepatitis C treatment regimens are now available. Despite reported high efficacies and better safety profiles, the impact of these regimens on PROs was unknown until recently. In the March issue of the Journal of Hepatology, Zobair M. Younossi, MD and colleagues present results from a study to assess the impact of treatment with ledipasvir (LDV) and sofosbuvir (SOF) with or without RBV on quality of life, work productivity and other patient-reported outcomes (Younossi ZM, et al. Hepatology. 2015 Jan 27 [Epub ahead of print]). The PRO data used in this study were collected from patients participating in three phase 3 clinical trials of SOF + LDV with and without RBV, which were conducted in the US, Spain, Germany, France, Great Britain, and Italy in 2013-2014 (ION-1, ION-2, and ION-3). The positive results of the trials have been previously reported in the New England Journal of Medicine (Afdhal N, et al. N Engl J Med. 2014 May 15;370(20):1889-1898; Afdhal N, et al. N Engl J Med. 2014 Apr 17;370(16):1483-1493; Kowdley KV, et al. N Engl J Med. 2014 May 15;370(20):1879-1888). Treatment-naive or experienced patients with genotype 1 chronic HCV infection were randomized to receive 400 mg of SOF plus 90 mg of LDV once-daily with or without weight-based ribavirin twice-daily (1,000 or 1,200 mg/day) for 8, 12, or 24 weeks.
- PRO scores actually improved during treatment with the IFN-free and RBV-free regimen containing LDV/SOF. This improvement was documented as early as 2 weeks after the initiation of treatment, and continued to improve throughout the entire duration of treatment.
- A longer duration of treatment with LDV/SOF (up to 24 weeks) was not found to be associated with any additional PRO burden.
- Most of the PRO improvements (for a large number of PRO domains) seen with LDV/SOF not only met statistical significance but also met the minimally clinically important difference (MCID). MCID denotes the changes in PRO scores that are clinically important rather than just statistically different.
- Baseline fatigue, depression, anxiety and cirrhosis were the most consistent independent predictors of PRO at all time points before, during, and after treatment. This is similar to what has been previously reported with on-treatment fatigue driving impairment in work productivity and other PROs.
- By improving fatigue during treatment and after SVR-12, patients’ work productivity was improved.
- On-treatment PRO scores for RBV-containing regimens (LDV/SOF + RBV) were inferior.
- PRO decrements in patients receiving LDV/SOF + RBV, although present, were substantially smaller in magnitude than those in IFN-containing regimens.
IFN-free and RBV-free regimens not only did not cause any PRO impairment, they were also associated with PRO improvement. This is the first study to provide support for the hypothesis that hepatitis C virus itself is responsible for a major component of PRO impairment. Although LDV/SOF + RBV may suppress the virus equally early, RBV-induced side effects (anemia, fatigue) negate this potential PRO benefit.
- Patients who achieved SVR-12 benefitted from significant PRO improvement. These gains occurred regardless of the treatment regimen (RBV-free or RBV-containing) suggesting that, by 12 week post-treatment, the negative impact of RBV-related side effects on PROs had been washed off.
The superior patient experience with IFN-free and RBV-free chronic hepatitis C treatment regimens containing LDV/SOF is clearly documented in this study. These improvements occur early during treatment and coincide with early viral suppression.