In people who have hepatitis C type 1, adding telaprevir, boceprevir, simeprevir, or sofosbuvir to usual treatment may improve response to treatment and increase side-effects

Kohli A, Shaffer A, Sherman A, et al. Treatment of hepatitis C: a systematic review. JAMA. 2014;312:631-40.

Review questions

Which medications best treat hepatitis C (HVC) infection? What are their adverse effects?

Background

Hepatitis C is a viral infection that damages the liver. People with HVC may not have symptoms, or they may have fatigue, muscle aches, loss of appetite, weight loss, fever, rashes on their palms, difficulty with blood clotting, spider veins, jaundice, and, in men, enlargement of breasts. HVC may eventually cause liver cancer.

There are 6 main types (genotypes) of HVC. In North America, HVC type 1 is most common, followed by types 2 and 3. Response to treatment varies by type.

How the review was done

The researchers did a systematic review, searching for studies available up to May 2014. They found 41 studies, including 33 randomized controlled trials, with 19,063 patients.

People in the trials had HCV genotype 1, 2, or 3 and could be treatment-naïve (had never received medication for HCV), null-responders (had a very small response to treatment), nonresponders (virus continued to be detectable in the blood after treatment), partial responders (had a response to HCV medication, but virus was still detectable), or relapsers (had a response to previous medication, but virus was detectable after treatment stopped).

Treatments included telaprevir (Incivek®) boceprevir (Victrelis®), simeprevir (Olysio®), or sofosbuvir (Solvadi®) added to pegylated interferon plus ribavirin (Copegus®, Rebetol®, Ribasphere®, Virazole®).

Treatments were compared with pegylated interferon plus ribavirin alone.

What the researchers found

Many comparisons had evidence of poor quality. Only effectiveness findings based on high strength of evidence are reported here.

The effectiveness of treatment was measured by a sustained virologic response, which means that the HCV virus could not be detected in the blood.

People with HCV genotype 1

All people were treated with pegylated interferon plus ribavirin.

Adding telaprevir improved responses in people who were treatment-naïve, null-responders, nonresponders, or relapsers. In treatment-naïve people who received all 3 medications, a shortened treatment duration based on response did not differ from fixed-duration treatment.

Adding boceprevir improved responses in people who were treatment-naïve, partial-responders, or relapsers. In treatment-naive people, partial responders, and relapsers who received all 3 medications, a shortened treatment duration based on response did not differ from fixed-duration treatment.

Adding simeprevir improved responses in people who were treatment-naïve, null-responders, partial-responders, or relapsers. In relapsers who received all 3 medications, a shortened treatment duration based on response improved response more than 48 weeks of treatment.

Adding sofosbuvir improved response in people who were treatment-naïve. In treatment-naïve people who received all 3 medications, 24 weeks of therapy did not differ from shorter-duration treatment.

People with HCV genotype 2 or 3

In people with genotype 2, sofosbuvir plus ribavirin for 12 weeks improved response more than pegylated interferon plus ribavirin for 24 weeks.

In people who were treatment-naïve and people who had previously been treated, sofosbuvir plus ribavirin for 24 weeks improved response more than the same treatment for 12 weeks in genotype 3 but not genotype 2.

Side-effects

Adding telaprevir, boceprevir, simeprevir, or sofosbuvir to pegylated interferon plus ribavirin may increase side-effects such as rashes, insomnia, anemia, fatigue, nausea, diarrhea, and neutropenia (low white blood cell count). Adding telaprevir or boceprevir may also increase discontinuation of medication.

Conclusion

In people who have hepatitis C type 1, adding telaprevir, boceprevir, simeprevir, or sofosbuvir to pegylated interferon plus ribavirin may improve response to treatment but may also increase risk of side-effects.

Effect of adding medications to pegylated interferon plus ribavirin on sustained virologic response* in people with hepatitis C genotype 1

*Sustained virologic response = elimination of the HCV virus from the blood.