BACKGROUND & AIMS: The combination of sofosbuvir and velpatasvir is used to treat patients with hepatitis C virus (HCV) infection of different genotypes. We compared the effects of this treatment regimen, with and without ribavirin, on outcomes reported by patients (patient-reported outcomes [PROs]) with HCV infection, with or without cirrhosis.
METHODS: We performed a post hoc analysis of data collected from phase 3 clinical trials (ASTRAL-1, -2, -3, and -4) of 1701 patients infected with HCV of different genotypes treated with sofosbuvir and velpatasvir with ribavirin for 12 weeks (n = 87), sofosbuvir with ribavirin for 12 or 24 weeks (n = 401), and ribavirin-free sofosbuvir and velpatasvir for 12 or 24 weeks (n = 1213). In all trials, participants completed 4 PRO questionnaires (while blinded to their HCV RNA levels): the Short Form-36, the Functional Assessment of Chronic Illness Therapy-Fatigue, the Chronic Liver Disease Questionnaire-HCV Version, and the Work Productivity and Activity Impairment: Specific Health Problem, at multiple time points. We compared baseline PROs and changes in PROs following treatment in patients without cirrhosis (n = 1112), with compensated cirrhosis (n = 338), and with decompensated cirrhosis (n = 251).
RESULTS: Baseline PRO scores were as much as 33.5% lower in patients with decompensated cirrhosis than in patients without cirrhosis (P < .05). Following treatment with ribavirin-containing regimens, changes in PRO scores were similar among patients with compensated and decompensated cirrhosis (all P > .01). Treatment with these regimens increased some PRO scores by as much as 11.8% from baseline (P < .05) and reduced others, by as much as 7.1% (P < .05). Despite this, by 12 weeks after cessation of treatment with ribavirin-containing regimens, all PRO decrements resolved; PRO scores increased by as much as 14.2%, and as much as 17.1% at 24 weeks after treatment, regardless of cirrhosis status (all P > .01 between cirrhosis groups). In contrast, treatment with ribavirin-free sofosbuvir and velpatasvir increased PRO scores for patients with compensated cirrhosis, and even more so in patients with decompensated cirrhosis starting at treatment Week 4; no statistically significant decrement was observed at any time point (all 1-sided P values > .05). In multivariate analysis, compensated cirrhosis was associated with a 2.3% to 5.0% greater increase in PRO scores following treatment with sofosbuvir and velpatasvir (P < .05); decompensated cirrhosis was associated with a 5.5%-9.1% greater increase (P < .002). Clinicaltrials.gov number, NCT02201940, NCT02220998, NCT02201953, NCT02201901.
CONCLUSIONS: In an analysis of data from 4 phase 3 clinical trials, we found that patients with HCV infection (especially those with decompensated cirrhosis) have significant increases in their PRO scores during treatment with sofosbuvir and velpatasvir and after achieving a sustained virologic response.
- Journal Article