The addition of ribavirin to the combination of sofosbuvir, velpatasvir, and voxilaprevir for treatment of direct-acting antiviral (DAA) failure did not improve sustained virological response (SVR) rates in patients with hepatitis C virus (HCV) and was associated with more adverse events, according to study results in the Journal of Hepatology.
Researchers conducted a randomized controlled trial (ClinicalTrials.gov Identifier: NCT04695769) to compare sofosbuvir, velpatasvir, and voxilaprevir with or without ribavirin in patients with chronic HCV who failed to respond to first-line DAA therapy.
Participants were adult patients (aged ≥18 years) with chronic hepatitis C that was detectable by HCV RNA polymerase chain reaction (PCR) after completing a previous DAA regimen. They were also eligible for antiviral treatment.
The patients were randomly assigned 1:1 to receive a fixed-dose combination of sofosbuvir, velpatasvir, and voxilaprevir (group A) or a fixed-dose combination of sofosbuvir, velpatasvir, and voxilaprevir with ribavirin (1,000 or 1,200 mg daily based on the patient’s body weight: <75 kg or >75 kg) (group B). The treatment duration was 12 weeks in the 2 groups.
The primary endpoint was treatment efficacy, which was defined as the achievement of SVR-12 confirmed by undetectable HCV RNA by PCR 12 weeks after the end of treatment.
Group A included 158 patients in the intention-to-treat (ITT) protocol and 141 in the per protocol (PP) analysis, and group B included 157 participants in the ITT protocol and 140 in the PP analysis. The overall mean age of participants was 49.6 years, and 55.5% were men. The sofosbuvir, velpatasvir, and voxilaprevir group had a higher proportion of patients with a fibrosis-4 (FIB-4) less than 1.45 vs the ribavirin group (35.5% vs 17.1%) and a greater proportion of patients with a FIB-4 greater than 3.25 (53.9% vs 20%).
The overall SVR rates in the 2 treatment groups were not different. The SVR12 in group A was 87.3% (138/158) in the ITT and 97.9% (138/141) in the PP analyses. In group B, the corresponding rates were 87.9% (138/157; P = .88) and 98.6% 138/157; P = .66). The ribavirin-containing group had an increased rate of adverse events (77 vs 55, P = .002), with fatigue and headache the most common side effects. No deaths occurred, and 1 serious adverse event of anemia that required hospitalization occurred in the ribavirin group.
In stratification with cirrhosis, no differences were observed in efficacy or adverse events between the 2 groups. For a subgroup of patients with FIB-4 greater than 3.25, no statistical difference was found in the rate of SVR12 between patients who received ribavirin (28/28) and those who did not (21/23) (P = .198). No difference occurred in the rate of adverse effects between the ribavirin group (n=13) and those without ribavirin (n=14); (P = .288)
Study limitations include the absence of genotyping for all patients, as well as missing SVR data in about 11% of both cohorts. In addition, FIB-4 was used to estimate the prevalence of cirrhosis.
“Addition of ribavirin to SOF/VEL/VOX [sofosbuvir, velpatasvir, and voxilaprevir] increased adverse events but not SVR rates in retreatment of patients who failed DAA therapy,” the researchers wrote. “Therefore, the preferred retreatment strategy should be SOF/VEL/VOX monotherapy.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
El-Kassas M, Emadeldeen M, Hassany M, et al. A randomized controlled trial of SOF/VEL/VOX with or without ribavirin for retreatment of chronic hepatitis C. J Hepatol. Published online April 21, 2023. doi:10.1016/j.jhep.2023.04.011