Daclatasvir-Sofosbuvir-Ribavirin Combination Similar to VEL/SOF Plus RBV for Hepatitis C Genotypes

Lisa Backus, MD, PhD

In patients with hepatitis C virus (HCV) genotype 2 and genotype 3, treatment regimens comprised of daclatasvir plus sofosbuvir plus ribavirin (DCV+SOF±RBV) and velpatasvir/sofosbuvir (VEL/SOF) plus RBV confer similar efficacy profiles in terms of achieving a cure, according to a new study.

Predictors for sustained virologic response (SVR) in genotype 3 patients treated with these regimens, according to the researchers, include prior HCV treatment, FIB-4 >3.25, and history of decompensated liver disease.

“Given the size of the cohort, we were able to discern differences among these treatment regimens which are widely used throughout the world, particularly among treatment-experienced patients, thus providing germane information on their effectiveness in genotype 2 and genotype 3 populations to better inform HCV management strategies,” leading study author, Lisa Backus, MD, PhD, told MD Magazine®. “We believe these findings are relevant to an extensive audience, including environments where wide access to all regimens are not readily available.”

Backus noted that, while DCV+SOF is not widely used in the US, investigators found it is as effective as VEL/SOF in difficult-to-treat subgroups.

For this observational study, investigators evaluated the effectiveness of DCV+SOF±RBV or VEL/SOF±RBV between patients with genotype 2 and genotype 3 HCV patients receiving care at the Department of Veterans Affairs. Specified analyses were focused on patients receiving DCV+SOF (n = 255), VEL/SOF (n = 2230), DCV+SOF+RBV (n= 42), and VEL/SOF+RBV (n= 247).

In patients with HCV genotype 2, there were no differences in regard to SVRs in patients receiving DCV+SOF and VEL/SOF (94.5% vs 94.4%; P = .94) or between DCV+SOF+RBV and VEL/SOF+RBV (88.1% vs 89.5%; P = 1.00). Additionally, there were no differences among HCV genotype 3 patients in terms of the SVR between regimens comprised of DCV+SOF and VEL/SOF (90.8% vs 92.0%; P = .50) or DCV+SOF+RBV and VEL/SOF+RBV (88.1% vs 86.4%, respectively; P = .51).

There was no significant predictive effect of any treatment regimen for predicting the odds of SVR in either genotype 2 or genotype 3 patients. In genotype 3 patients, however, significant predictors associated with a decreased SVR odds included prior HCV treatment (odds ratio [OR] 0.51; 95% CI: 0.36 - 0.72; P < .001), FIB-4 >3.25 (OR 0.60; 95% CI: 0.43 - 0.84; P = .002), and a history of decompensated liver disease (OR 0.68; 95% CI: 0.47 - 0.98; P = .004).

“Because of the timeframe of this study, some regimens that were used were not a part of current HCV guideline recommendations as guidelines were either not updated at the time these patients were initiating treatment (mid 2015 to early 2017) because of the rapidity of emerging data or because guideline recommendations have since changed,” Backus explained.

As such, he stressed the importance of remember real-world providers may make decisions to extend treatment, add ribavirin, or use non-approved combinations.

Backus added that future research studies should focus on evaluating such outcomes with non-traditional regimens as potential therapy alternatives, particularly given the limited HCV drug pipeline.

“As new data emerges with expanded use of HCV antiviral agents, it is important to consider real-world data when updating HCV treatment guidelines, recognizing that inevitably not all patients will be treated as recommended in guidelines,” Backus said.

The study, "Real-world Effectiveness of Daclatasvir plus Sofosbuvir and Velpatasvir/Sofosbuvir in Hepatitis C Genotype 2 and 3," was published online in the Journal of Hepatology.