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Study shows low SVR among veterans on Sovaldi-based regimens

Veterans with hepatitis C virus infection genotype 1 or 2 were found to have lower sustained virologic response rates from Sovaldi-based regimens compared with rates reported from clinical trials of the same regimens, according to study findings.

“Monitoring and optimizing uptake, appropriate use and outcomes of HCV antiviral regimens is a priority for the Department of Veterans Affairs,” the researchers wrote. “With the rapid uptake of sofosbuvir-based regimens across healthcare settings, and the under-representation of important populations in clinical trials, we examined the real-world outcomes of the diverse HCV-infected veteran population receiving these regimens.”

Researchers from the Veterans Affairs Palo Alto Health Care System in Palo Alto, California, including Lisa Backus, MD, PhD, analyzed data obtained from the VA’s Clinical Case Registry for HCV of 4,026 veterans with HCV genotype 1 (n = 3,203) and 2 (n = 823) on sofosbuvir-based regimens for 12 weeks. The 12-week regimens examined included: Sovaldi (sofosbuvir, Gilead Sciences) plus pegylated interferon; PEG-IFN plus ribavirin; sofosbuvir plus Olysio (simeprevir, Janssen Therapeutics) with or without ribavirin; and sofosbuvir plus ribavirin.

Lisa Backus

“We observed SVR rates lower than reported in clinical trials for either genotype, although still substantially higher than rates reported previously in similar VA cohorts with earlier generations of HCV antiviral treatments,” Backus told Healio.com/Hepatology. “Our results indicate that the new treatments do represent substantial improvements in HCV antiviral treatment.”

In genotype 1 patients, those on a sofosbuvir plus simeprevir or sofosbuvir with simeprevir plus ribavirin regimen had advanced liver disease and were more likely to have a history of decompensated liver disease compared with those on a regimen of sofosbuvir plus PEG-IFN and ribavirin (P < .001 for both).

Kaplan-Meier analysis showed that 13.7% of genotype 1 patients on a regimen of sofosbuvir with PEG-IFN plus ribavirin, 11.8% on a regimen of  sofosbuvir and simeprevir and 9.9% of patients on sofosbuvir with simeprevir plus ribavirin, discontinued therapy prior to 12 weeks. Among the genotype 2 patients, 14.3% on a sofosbuvir plus ribavirin regimen discontinued therapy before 12 weeks.

SVR rates were 66.8% for patients on a sofosbuvir with PEG-IFN plus ribavirin regimen; 75.3% for sofosbuvir and simeprevir; and 74.1% for sofosbuvir with simeprevir plus ribavirin. Overall, SVR rates between the sofosbuvir and simeprevir regimen and sofosbuvir with simeprevir plus ribavirin were not different (P = .75). SVR rates were higher among patients on a regimen of sofosbuvir with simeprevir with or without ribavirin compared with patients on sofosbuvir with PEG-IFN plus ribavirin (75.1% vs. 66.8%; P < .001).

“Genotype 1 and 2 HCV-infected veterans with advanced liver disease, prior treatment experience or detectable week 4 on-treatment HCV RNA were significantly less likely to achieve SVR,” the researchers wrote. “For genotype 1, use of [sofosbuvir plus simeprevir with or without ribavirin] was associated with a higher likelihood of SVR compared with sofosbuvir with [PEG-IFN plus ribavirin].”

The researchers concluded: “We observed SVR rates lower than reported in clinical trials for either genotype although still substantially higher than rates reported previously in similar VA cohorts with boceprevir- or telaprevir-based regimens.

“Patients and providers should temper their expectations as the sustained virologic response rates in routine medical practice will likely not be as high as in the clinical trials,” Backus said. “Part of this apparent decrement in effectiveness may be explained by differences in patient populations as patients treated in routine medical practice may not have met the stringent entry criteria for clinical trials.  Furthermore, there are likely differences in practice patterns, patient motivation, provider knowledge, provider resources and ancillary services in routine medical practice compared to highly-structured, highly-resourced clinical trials.” – by Melinda Stevens

Disclosures: The researchers report no relevant financial disclosures.