An 8-week regimen of sofosbuvir plus ledipasvir was found to be effective for many hepatitis C patients in real-world studies, even those who did not meet the official criteria for the shortened treatment. A review of five real-world studies involving over 600 patients found sustained viral response rates of 97% or higher with the 8-week regimen. The results provide reassurance that clinical trial results translate to real-world practice and suggest the criteria for the 8-week regimen could be expanded.

1. Shortened Hep C Combo Passes Real-World Test
Laird Harrison
|March 18, 2016
SAN FRANCISCO — An 8-week regimen of the combination of sofosbuvir plus ledipasvir (Harvoni,
Gilead Sciences) could be an option for many patients with hepatitis C, even those who don't meet
the approved criteria for the shortened regime, new research shows.
Most clinicians still prescribe the combination for 12 or 24 weeks, said Norah Terrault, MD, from the
University of California, San Francisco. But the drugs are expensive, so an 8-week regimen saves
money and it cuts down on patient visits.
"We should be doing more of it," she told Medscape Medical News.
The 8-week regimen has been approved for treatment-naïve patients with genotype 1 hepatitis C
infection, no cirrhosis, and viral loads below 6 million IU/mL by the US Food and Drug Administration
(FDA) and the European Medicines Agency.
Still, some clinicians can be reluctant to prescribe such a short regimen because of concern that trial
results will not be reflected in a real-world practice, she said.
To see if that is cause for concern, Dr Terrault and her colleagues compared results from ION-3, a
clinical trial of the 8-week regimen, with five real-world studies — HCV-TARGET, TRIO, and VA-Ohio
from the United States, and the GECCO and Buggisch studies from Germany.
Dr Terrault presented the results of the comparison here at the International Conference on Viral
Hepatitis 2016.
ION-3 Patients
The post hoc analysis of ION-3 data involved 123 patients who met the FDA-approved criteria for
and completed an 8-week regimen of the combination, and a matched cohort of 126 patients who
completed a 12-week regimen. Sustained viral response at 12 weeks was essentially the same with
the 8-week and 12-week regimens (97% vs 96%). Relapse rates were also similar with the two
regimens.
But there were ION-3 patients who did not meet the FDA-approved criteria who still fared well with
the 8-week regimen, Dr Terrault reported. For patients with a viral load above 6 million IU/mL, a
sustained viral response at 12 weeks was achieved by 95% of patients who received ribavirin in
addition to the combination, and by 100% of patients who did not receive ribavirin. Results for
patients with fibrosis up to stage 3 were just as good.
TARGET Patients
In the TARGET cohort, 323 patients met the criteria for the 8-week regimen, but 192 were assigned
by their physicians to a 12-week regimen. This shows how underused the 8-week regimen is, Dr
Terrault pointed out. The rate of sustained viral response at 12 weeks was the same with the 8-week
and the 12-week regimens (97% vs 97%).
Not all TARGET patients treated with the 8-week regimen met the FDA criteria. Six of the 154
patients (those with incomplete data were excluded from the previous analysis) had stage 4 fibrosis,
and eight had received previous treatment.

2. And in the TRIO cohort, eight of the 263 patients had viral loads above 6 million IU/mL.
Evidence Mounting
The GECCO study involved the most patients who did not meet the FDA criteria: seven patients were
coinfected with HIV, three had stage 4 fibrosis, 12 had been previously treated, and nine had a high
viral load. But all of these patients achieved a sustained viral response at 12 weeks.
Overall, in the five real-world studies, a combined 620 patients had a sustained viral response at 12
weeks of 97% or better with the 8-week regimen.
It's compelling to see it acrossso many studies.
"It's compelling to see it across so many studies," said Dr Terrault. "I think this will encourage more
providers to do the 8 weeks."
It is possible that the viral load specified in the criteria should be higher. "Six million seems like an
arbitrary cutoff," she said, but limiting the 8-week regimen to treatment-naïve patients with no
cirrhosis seems sensible.
Failure rates in all studies of a 6-week regimen have been high, she reported.
After the presentation, a member of the audience described a case of failure with the 8-week
regimen, but it turned out that physicians had overlooked the patient's cirrhosis because they did not
have an elastography machine.
Clinicians who don't have access to elastography equipment have to rely on serum biomarkers,
"which we know can work both ways — overestimating and underestimating fibrosis," Dr Terrault
explained.
"We actually spend a lot of time educating our providers about using the various scores to help make
that decision," she said. "But I think the message we leave them with is that if you're unsure and you
think there could be a higher stage, err on the side of treating them for 12 weeks."
Another audience member asked whether the treatment failures in these studies were related to a
lack of adherence or to virologic failures.
Dr Terrault reported that treatment adherence was very high and that the treatment failures appeared
to be related to relapses.
These findings "add reassurance" for clinicians using this regimen in patients who meet the criteria,
session moderator Ji-Dong Jia, MD, PhD, from Capital Medical University in Beijing, told Medscape
Medical News.
Dr Terrault reports relationships with AbbVie, Achillion Pharmaceuticals, Biotest, Bristol-Myers
Squibb, Eisai, Gilead Sciences, Janssen Pharmaceuticals, Merck, Cocrystal, and UpToDate. Dr Jia
reports relationships with AbbVie, Bristol-Myers Squibb, Gilead Sciences, and Roche Laboratories.
International Conference on Viral Hepatitis (ICVH) 2016: Abstract 25. Presented March 14, 2016.