Treatment with ledipasvir and sofosbuvir improves patient‐reported outcomes: Results from the ION‐1, ‐2, and ‐3 clinical trials

Abstract

Treatment with interferon (IFN) and ribavirin (RBV) significantly impairs quality of life and other patient-reported outcomes (PROs). Patient experience with IFN-and RBVfree anti-HCV (hepatitis C virus) regimens has not been reported. We assessed PROs in patients treated with ledipasvir and sofosbuvir (LDV/SOF) with and without RBV. Four different PRO questionnaires were administered at baseline, during, and post-treatment in HCV genotype 1 patients treated with LDV/SOF6RBV (ION-1, -2, and -3). A total of 1,952 patients were enrolled to be treated for 8 (N 5 431), 12 (N 5 867), or 24 weeks (N 5 654) with LDV/SOF (N 5 1,080) or LDV/SOF1RBV (N 5 872). Baseline demographics and psychiatric disorders were similar between treatment groups (all P > 0.05). Patients receiving LDV/SOF regimens showed significant improvement of PRO scores during treatment (up to 17.4%, 17.0%, and 16.7% on a normalized 0%-100% scale in the 8-, 12-, and 24-week-long treatment groups, respectively (all P < 0.0001). These PRO improvements coincided with early viral suppression after 2 weeks of treatment and maximized by the end of treatment. On the other hand, during treatment with LDV/SOF1RBV, PRO scores declined (up to 25.5% regardless of treatment duration; P < 0.0001). Receiving RBV was an independent predictor of PRO impairment in multivariate analysis (beta up to 25.9%; P < 0.0001). Patients who achieved sustained virological response at 12 weeks showed significant improvement of their PROs post-treatment (up to 18.3%; P < 0.0001). Conclusion: IFN-and RBV-free regimens with LDV/SOF result in early HCV suppression with simultaneous improvement in PROs that continued throughout the duration of treatment and post-treatment.

Current and future challenges in HCV: insights from an Italian experts panel

“…In general, by curing HCV, patient-reported outcomes (PROs) return to values similar to a healthy population. These findings are in line with the observation of patient-related assessments following treatment with sofosbuvir/ledipasvir with and without ribavirin [154]. Patients receiving this regimen showed significant improvement of PROs that coincide with early viral suppression after 2 weeks of treatment and maximized by the end of treatment.…”

The Optimal Timing of Hepatitis C Therapy in Transplant Eligible Patients with Child B and C Cirrhosis: A Cost-Effectiveness Analysis

“…There is evidence that successful treatment leads to increases patient-reported quality of life (QOL). 6 We used a conservative estimate that 57% of subjects obtaining SVR would experience an 0.026 increase in their reported annual utilities. 19 For the probabilistic sensitivity analyses, the proportion of patients attaining a QOL benefit was modelled as a beta distribution and the magnitude of QOL benefit was modelled as a triangular distribution 0.026 (0.00 -0.026).…”

“…6 Similarly, the natural history of decompensated cirrhosis following SVR is not fully understood. We assigned the same MELDbased risk of death and transplant to patients with and without SVR.…”

“…[1][2][3][4][5][6] The standard of care has progressed from frequent treatment failures to readily available cures with rare adverse events. 7,8 While many important questions remain, 2 of the greatest relate to the cost-effectiveness and coverage of treatment 9 and the timing of therapy for those undergoing evaluation for liver transplantation.…”

Direct antiviral agent treatment of decompensated hepatitis C virus-induced liver cirrhosis

“…Most IFN-free DAA trails up to now have enrolled only a modest population (10%-20%) of cirrhotics with wellcompensated diseases [15,20,25,26] . SVR rates for cirrhotics in these studies were comparable to those of non-cirrhotic patients, in contrast to the result of IFN-based regimens, for which, as fibrosis of liver progresses, the rate of SVR decreases and the incidence of adverse effects increases.…”