"Sofosbuvir–Ribavirin for Hepatitis C Genotype 2 or 3 in Patients without Treatment Options".The New England Journal of Medicine. 2014.

Clinical Question

Does treatment with sofosbuvir-ribavirin for hepatitis C virus (HCV) genotypes 2 or 3 result in high rates of sustained virologic response in patients in need of a treatment option other than interferon?

Bottom Line

Treatment with sofosbuvir-ribavirin for 12 weeks in patients with HCV genotype 2 infection and for 24 weeks in patients with HCV genotype 3 infection led to high rates of sustained virologic response, providing an alternative to interferon-based regimens.

Major Points

Patients with HCV genotype 2 or 3 infection often have limited treatment options, especially those who have contraindications to interferon or have previously failed interferon-based therapy. The combination of sofosbuvir, a nucleotide polymerase inhibitor, and ribavirin has shown promise in clinical trials, particularly for these genotypes. This study aimed to assess the efficacy of sofosbuvir-ribavirin in these patient populations, with an original 12-week treatment plan revised during the course due to emerging evidence to 24-weeks for genotype 3 infection. A sustained virologic response was achieved in 93% of genotype 2 patients treated for 12 weeks and 85% of genotype 3 patients treated for 24 weeks, providing an effective interferon-free therapy option.

Guidelines

As of August 2017, no updated guidelines reflecting the results of this trial have been published regarding the use of sofosbuvir-ribavirin for the treatment of HCV genotypes 2 or 3.

Design

Multicenter, descriptive study initially designed as a phase 3 trial, later amended to a descriptive study without hypothesis testing due to treatment duration changes based on emerging evidence.
N=419 patients with HCV genotype 2 or 3 infection

Interventions:

- Sofosbuvir (400 mg daily) plus weight-based ribavirin for 12 weeks in genotype 2 infection (n=73)
- Sofosbuvir (400 mg daily) plus weight-based ribavirin for 24 weeks in genotype 3 infection (n=250)
Primary endpoint: Sustained virologic response at 12 weeks post-therapy

Population

Inclusion Criteria:
- Age ≥18 years
- Chronic HCV genotype 2 or 3 infection with serum HCV RNA levels ≥10,000 IU/mL
- Eligible regardless of prior interferon-based therapy
- Approximately 20% could have cirrhosis.

Exclusion Criteria:
- Major exclusion criteria detailed in the Supplementary Appendix.

Baseline Characteristics
- Gender: 40% female
- Cirrhosis: 21%
- Previously treated for HCV infection: 58%
- Characteristics balanced between genotype 2 and 3 patients.

Interventions

- Sofosbuvir (400 mg daily) orally plus ribavirin orally twice daily for either 12 or 24 weeks depending on HCV genotype.

Outcomes

- Primary Outcome: Sustained virologic response at 12 weeks post-therapy
- Genotype 2 infection: 93% achieved sustained virologic response after 12-week treatment
- Genotype 3 infection: 85% achieved sustained virologic response after 24-week treatment

Criticisms

- Original randomized controlled trial design changed due to evolving evidence, leading to a lack of hypothesis testing or formal statistical comparisons.
- Lack of liver biopsy data limits the understanding of liver disease extent and subgroups that might benefit from longer or add-on therapy.

Funding

Supported by Gilead Sciences.

Further Reading

- Detailed study protocol and additional data available in the Supplementary Appendix on NEJM.org.