Real-world high SVR rates with ledipasvir/sofosbuvir±ribavirin and ombitasvir/parataprevir/ritonavir+dasabvir±RBV mirror efficacy found in clinical trials for HCV

Liz Meszaros, MDLinx

Digestive Disease Week® (DDW)

San Diego, California, United States | May 21-24, 2016

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San Diego, CA, May 22, 2016—In this real-world study conducted to assess the comparative efficacy of ledipasvir/sofosbuvir±ribavirin (LS±RBV) and ombitasvir/parataprevir/ritonavir + dasabvir (OPrD) ±RBV in patients with genotype 1 (GT1) hepatitis C virus (HCV), GT1 patients had high sustained virologic response (SVR) rates similar to those found in clinical trials, according to data study presented here at Digestive Disease Week 2016.

Take-home messages

  • Genotype 1 hepatitis C virus patients had high sustained virologic response rates similar to those found in clinical trials after 12-week treatment with ledipasvir/sofosbuvir ± ribavirin (LS±RBV) and ombitasvir/parataprevir/ritonavir+dasabvir (OPrD) ±RBV.
  • Patients needed to take the full 12-week course of therapy with these agents to achieve the high efficacy found in clinical trials.

In addition, lead researcher Lisa I. Backus, deputy chief consultant of Measurement and Reporting, Patient Care Services/Population Health Services, Department of Veterans Affairs, and Department of Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, and fellow researchers found that African Americans, those with a high body mass index (BMI), those with prior decompensation, and those treated with OPrD+RBV had a reduced odds of SVR. These associations, however, may have been caused by early discontinuations, they noted, because they had no impact on the odds of SVR in subjects who completed a 12-week course of treatment. Fibrosis-4 scores (FIB-4) greater than 3.25 did, however, remain a significant negative predictor.

“The reason we conducted this study is because there are these new medications for HCV that, in the clinical trials, have had incredibly high SVR rates. However, in the past, we have noted that agents in the real world don’t perform quite as well as they do in clinical trials, because in the real world, you have patients who are slightly more difficult to treat, you have more competing co-morbidities, you have providers who don’t have as much time,” explained Dr. Backus. “We wanted to see if the clinical effectiveness in the real world was as good as the clinical efficacy that we’d seen in the clinical trials.”

Dr. Backus and colleagues conducted this observational, intent-to-treat study to assess the comparative efficacy of LS±RBV and OPrD ±RBV in patients with GT1 HCV who were treated in routine medical practice. They identified 6,961 GT1 patients who had started 8 or 12 weeks of LS±RBV, or 12 weeks of OPrD±RBV by March 31, 2015, and end of treatment (EOT) by July 14, 2015, and a days’ supply ≤ 91 using the Veterans Affairs’ Clinical Case Registry.

These researchers excluded patients who had undergone liver transplantation or who had a baseline RNA < 1000 IU/mL. RNA results under the limit of detection for test at least 10 weeks after end of treatment were required for SVR. Researchers constructed multivariate models of SVR, including age, sex, race/ethnicity, BMI, prior decompensations, diabetes, previous treatment, genotype subtype, FIB-4, and regimen.

In all, 4,478 patients initiated LS, 1,269 LS+RBV, 297 OPrD who were exclusively GT1B, and 917 OPrD+RBV. Patients were from 126 facilities, with a mean age of 61.4 years; 96.3% male; 36.0% black; 23.6% treatment experienced, and 29.5% with FIB-4 > 3.25. Researchers had SR data available for 89% of subjects.

For LS overall, SVR rates were 90.9%, 90.1% for LS+RBV, 95.1% for OPrD, and 87.0% for LS+RBV, they reported. In subjects with FIB-4 > 3.25, SVR was 86.8% for LS, 87.9% for LS+RBV, 94.2% for L+RBV, 92.6% for OPrD, and 85.7% for OPrD+RBV. When this was limited to those who received 8 weeks of LS, researchers found SVR rates of 91.2%. In those completing 12 weeks of treatment, 94.2% for LS, 92.4% for LS+RBV, 97.9% for OPrD, and 95.4% for OPrD+RBV.

Dr. Backus and colleagues found that black race (OR: 0.74; 95% CI: 0.61-0.90; P=0.002), BMI greater than 30 kg/m2 compared with 25-29 kg/m2 (OR: 0.72, 95% CI: 0.58-0.88; P=0.001), prior decompensation (OR: 0.59, 95% CI: 0.40-0.89; P=0.008), subtype 1b (OR: 1.44, 95% CI: 1.15-1.80; P=0.001), FIB-4 greater than 3.25 (OR: 0.61, 95% CI 0.50-0.74; P less than 0.01), and OPrD+RBV compared to LS (OR: 0.71, 95% CI: 0.55-0.90; P=0.004).

Upon multivariate modeling of only those subjects receiving 12 weeks of treatment, they found that FIB-4 greater than 3.25 remained the only significant predictor (OR: 0.49, 95% CI: 0.37-064; P < 0.001).

“These drugs work as well in the real world as they did in clinical trials. For us, this is a stunning result. We have never seen clinical effectiveness nearly this high and nearly as close to what we see in the clinical trials,” said Dr. Backus.

“The other take-home message is, not surprisingly, that adherence really matters, and that it’s really important to get patients to take their 12 weeks of medications. If you can get them to take 12 weeks, the medications work incredibly well, and some of the factors that had previously predicted decreased response rates no longer pan out if you can get the patients to take the full 12 weeks,” Dr. Backus concluded.

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