Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Nov.
Report No.: 12(13)-EHC113-EF.
comparative benefits and harms of current antiviral treatment regimens for
chronic hepatitis C virus (HCV) infection in treatment-naïve adults.
(1947 to August 2012), the Cochrane Central Register of Controlled Trials
(through 3rd quarter 2012), clinical trial registries, and reference
criteria to determine study eligibility. We selected randomized trials of dual
therapy with pegylated interferon (alfa-2a or alfa-2b) plus ribavirin or triple
therapy with pegylated interferon (alfa-2a or alfa-2b), ribavirin, and either boceprevir
or telaprevir that reported clinical outcomes, sustained virologic response
(SVR), or harms. We also selected randomized trials or cohort studies that
compared clinical outcomes in patients who experienced an SVR after antiviral
therapy with patients who did not experience an SVR.
evaluated the comparative effectiveness of current antiviral regimens on
long-term clinical outcomes. In trials of treatment-naïve patients, the
likelihood of achieving an SVR was slightly lower for dual therapy with
pegylated interferon alfa-2b plus ribavirin than for dual therapy with
pegylated interferon alfa-2a plus ribavirin, with a difference in absolute SVR
rates of about 8 percentage points. There were no clear differences in
estimates of relative effectiveness in patient subgroups defined by demographic
or clinical characteristics, although absolute response rates were lower in
older patients, Black patients, patients with high viral load, patients with
more advanced fibrosis or cirrhosis, and patients with genotype 1 infection.
Differences in harms were relatively small, with no difference in withdrawals
due to adverse events, although dual therapy with pegylated interferon alfa-2b
plus ribavirin was associated with a lower risk of serious adverse events than
dual therapy with pegylated interferon alfa-2a plus ribavirin. In patients with
genotype 2 or 3 infection, trials found dual therapy with pegylated interferon
for 12 to 16 weeks associated with a lower likelihood of achieving SVR as
compared with 24 weeks of therapy. Lower doses of pegylated interferon alfa-2b
were less effective than standard doses, and limited evidence showed no clear
differential effects of ribavirin dosing. Five trials found triple therapy with
pegylated interferon (alfa-2a or alfa-2b), ribavirin, and either boceprevir or
telaprevir associated with higher likelihood of SVR (66–80 percent) than dual
therapy with pegylated interferon plus ribavirin for genotype 1 infection, with
an absolute increase in SVR rate of 22–31 percentage points. Triple therapy
with boceprevir was associated with increased risk of hematological adverse
events, and triple therapy with telaprevir was associated with increased risk
of anemia and rash, including severe rash, versus dual therapy. A large cohort
study that controlled well for confounders found that patients with an SVR
after antiviral therapy had a lower risk of all-cause mortality than patients
with no SVR, with adjusted hazard ratio estimates ranging from 0.51 to 0.71,
depending on genotype. Other, smaller cohort studies also found that SVR was
associated with reduced risk of all-cause mortality and long-term complications
of HCV infection, but had more methodological shortcomings.
there is no direct evidence on the comparative effects of current antiviral
regimens on long-term clinical outcomes, SVR rates are substantially higher in
patients with HCV genotype 1 infection who receive triple therapy with pegylated
interferon (alfa-2a or alfa-2b), ribavirin, and boceprevir or telaprevir
compared with dual therapy with pegylated interferon plus ribavirin. Achieving
an SVR following antiviral therapy appears to be associated with decreased risk
of all-cause mortality compared with no SVR, although estimates are susceptible
to residual confounding.