In an oral abstract session devoted to currently approved HCV therapies,
Donald Jensen from the University of Chicago Medical Center presented findings
on the real-world experience of people undergoing treatment with sofosbuvir-containing
regimens in HCV-TARGET, a consortium of more than 50 academic and community
medical centres in the US, Canada and Germany.
A total of 2330 people with hepatitis C consented to be included in
HCV-TARGET, and of these 2063 started treatment. Nearly two-thirds were men,
76% were white, 12% were black and the average age was 58 years; 2% had HIV
co-infection. About half were previously untreated for hepatitis C and half
were treatment-experienced, including 18% who did not respond to a prior course
of triple therapy with first-generation protease inhibitors.
Given the high cost of sofosbuvir and simeprevir, and the various
restrictions on their availability and insurance coverage, experts recommend
that people with advanced liver disease be prioritised for treatment, and that
was reflected in this population. Nearly half (48%) had liver cirrhosis, 43%
had a history of decompensation and 34% had a MELD score >10. One in ten had
liver cancer and 11% had received a liver transplant. Overall, people who used
sofosbuvir plus simeprevir were sicker than those who used sofosbuvir with pegylated
interferon/ribavirin or with ribavirin alone.
Treatment was administered according to local standards of care, and patients
and providers chose which regimens to use:
- Sofosbuvir plus simeprevir (n = 784).
- Sofosbuvir plus ribavirin alone (n = 667).
- Sofosbuvir plus pegylated interferon/ribavirin (n = 384).
- Sofosbuvir/simeprevir/ribavirin (n = 228).
Treatment distribution varied by HCV genotype. Among people with
genotype 1, 53% used sofosbuvir plus simeprevir, 23% used sofosbuvir plus
pegylated interferon/ribavirin, 15% used sofosbuvir/simeprevir/ribavirin and 9%
used sofosbuvir with ribavirin alone. Almost everyone (99%) with
easier-to-treat genotype 2 received sofosbuvir with ribavirin alone. Genotype 3
is more difficult to treat but simeprevir is not effective against it, so 92%
of these patients also used sofosbuvir with ribavirin alone.
Overall, 78% of participants completed therapy and 18% were still on
treatment. Only 3% stopped treatment prematurely, mostly due to adverse events
(2.1%), and this was not more likely to occur among people taking interferon. Early
discontinuation due to lack of efficacy (0.4%), loss to follow-up (0.3%) or
death (0.6%) was rare.
Nelson reported sustained virological response rates for patients who
had reached week 4 after completion of treatment (SVR4). While SVR4 is
generally reflective of outcomes at 12 weeks post-treatment (SVR12), it is too
soon to declare a cure as relapse may still occur. Among the subset of patients
with both SVR4 and SVR12 results available (n = 259), concordance or agreement
was 94-98%.
Among evaluable genotype 1 patients treated with sofosbuvir plus
pegylated interferon/ribavirin (n = 164), the SVR4 rate was 85% (90% for people
without cirrhosis vs 70% for people with cirrhosis). Among people with HCV genotype
1 using sofosbuvir plus simeprevir with or without ribavirin (n = 303), the SVR4
rate was 89% (92% for people without cirrhosis vs 87% for people with cirrhosis
vs 75% for those with prior decompensation).
Further breaking down the genotype 1 population who used sofosbuvir plus
simeprevir, SVR4 rates were 86% for people with HCV subtype 1a and 95% for
those with easier-to-treat subtype 1b. Among evaluable patients with prior
treatment failure (n = 54), the SVR4 rate was 81% (85% for people without cirrhosis
vs 79% for people with cirrhosis).
Among genotype 2 patients treated with sofosbuvir plus ribavirin (n = 187),
the SVR4 rate was 90% (91% for people without cirrhosis vs 88% for people with cirrhosis).
Genotype 3 patients were not included in this report because most received
longer treatment and were still undergoing follow-up for sustained response.
In a minimally adjusted multivariate analysis, predictors of sustained
response to sofosbuvir plus simeprevir with or without ribavirin included HCV
subtype 1a, prior liver decompensation, lower baseline albumin level (a marker
of poor liver function) and prior treatment failure using triple therapy.
Across all patient subgroups using sofosbuvir plus simeprevir –
including the most difficult to treat people with genotype 1a HCV and cirrhosis
– adding ribavirin did not significantly increase response rates compared to
sofosbuvir plus simeprevir alone.
Overall, sofosbuvir-containing regimens were generally safe and
well-tolerated. Serious adverse events were uncommon across all regimens (2.9
to 7.9%).
The most frequent side-effects were fatigue, headache and nausea.
Flu-like symptoms were more common in the pegylated interferon arm, while
anaemia was reported more often among patients taking ribavirin.
"There
was a high percentage of 'off-label' use of sofosbuvir/simeprevir," and
real-world data were "generally consistent" with phase 2-3 clinical
trial data, the researchers concluded.
Adverse
event rates for all-oral regimens were "much lower" than those with pegylated
interferon, they added, with the lowest frequency observed for interferon-free
and ribavirin-free regimens.