Real-world responses to HCV treatment among U.S. veterans match stellar clinical trial results

Direct-acting antiviral treatment is curing people of hepatitis C in real-world clinical practice at similar rates to those seen in clinical trials, and there do not seem to be major differences between drug regimens, according to results of a large population study presented at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting in Boston.

Clinical trials tend to show the best-case scenario for efficacy of new drugs. Patients in clinical trials are carefully selected from populations who are already attending clinics — by definition, a highly motivated group of patients. Furthermore, patients recruited to clinical trials cost money to recruit and monitor, so they will be followed carefully and in many cases patients are getting free treatment, maximizing the incentive to stay in care. All these factors tend to promote better outcomes in clinical trial populations than in subsequent “real-world” clinic populations.

A review of the Veterans Affairs Cohort — military veterans receiving care through U.S. Veterans Affairs clinics — finds that patients receiving direct-acting antiviral (DAA) treatment in VA hospitals are being cured of hepatitis C at similar rates to those seen in clinical trials of the drug combinations in widespread use today.

Clinical trials that led to licensing of the DAA combinations currently recommended for treatment reported sustained virological response rates at 12 weeks post-treatment (SVR12) above 90% for HCV genotype 1, around 75% for genotype 3, and somewhat lower for each genotype in cases where people had liver cirrhosis or previous experience of unsuccessful treatment.

The study also found that an 8-week regimen of sofosbuvir/ledipasvir (Harvoni) is just as effective as a 12-week regimen for those who qualify to take it — genotype 1 patients without cirrhosis or previous treatment experience who have a HCV viral load below 6 million IU/mL.

The study population comprised 17,487 chronic hepatitis C patients who started therapy with DAAs without interferon between January 2014 and June 2015 at 167 VA medical centers. Follow-up continued through April 2016. The main study outcome was SVR. This was analyzed according to HCV genotype and cirrhosis status.

The study population was 97% male, 52% white, 29% black, 5% Hispanic, and had a high prevalence of cirrhosis (30%) and decompensated cirrhosis (8.3%). Genotype 1 was the predominant form of hepatitis C infection (80%), with 12% infected with genotype 2, 7% with genotype 3, and 1% with genotype 4.

Regimens used by the patients were:

  • Sofosbuvir/ribavirin (SOF/riba): n=2986;
  • Sofosbuvir/ledipasvir (SOF/LDV): n=11,327;
  • Paritaprevir/ritonavir/ombitasvir + dasabuvir (PrOD): n=3174.

The study measured sustained virological response rates 12 weeks after completion of treatment. If SVR12 data were missing, the SVR12 result was imputed from SVR4 measurements at 4 weeks post-treatment (5.7% of cases).

% treated SVR12 %
Genotype 1
SOF/LDV 58% 92%
SOF/LDV/riba 19% 92%
PrOD 6% 94.9%
PrOD/riba 17% 92.5%
Genotype 2
SOF/riba 100% 86.2%
Genotype 3
SOF/riba 57% 77.9%
SOF/LDV/riba 31% 87%
SOF/PEG/riba 11% 70.6%
Genotype 4
SOF/LED/riba 77% 87.6%
PrOD/riba 23% 96.4%

The study also looked at the performance of direct-acting antivirals in people with cirrhosis. Whereas in patients with HCV genotype 1 there was little difference in SVR12 rates between those with or without cirrhosis (90.6% vs 93.6%), virological response was considerably lower in cirrhotic patients with genotype 2 (77.3% vs 89.1%) and genotype 3 (65.7% vs 81.6%). Response was also lower in cirrhotic patients with genotype 4 (83.9% vs 91.5%), although less markedly so.

A similar pattern was evident when treatment responses were compared in treatment-experienced and previously untreated patients. There was no difference in virological response in genotype 1 patients, but SVR rates in treatment-experienced patients with genotypes 2 or 3 were around 8% lower than in previously untreated patients (80.2% vs 88% for genotype 2; 77.5% vs 69.2% for genotype 3).

The study also looked at treatment outcomes for 1975 patients who qualified for an 8-week course of sofosbuvir/ledipasvir — previously untreated, non-cirrhotic patients with viral load below 6 million IU/mL. 95.1% of these patients achieved SVR12, compared to 95.8% of those treated with sofosbuvir/ledipasvir for 12 weeks.

Independent predictors of treatment failure included genotype 2 or 3 infection compared to genotype 1, and among those with genotype 2 or 3 infection, treatment experience. Male sex, black or Hispanic race/ethnicity, diabetes, low platelet count, low serum albumin, and elevated bilirubin all independently predicted failure to achieve SVR, as did cirrhosis.

By Keith Alcorn

Source

GN Ioannou, LA Bester, M Chang, et al. Effectiveness of sofosbuvir, ledipasvir/sofosbuvir and paritaprevir/ritonavir/ombitasvir and dasabuvir-based antiviral regimens in 17,847 patients in the Veterans Affairs National Healthcare System. 67th Meeting of the American Association for the Study of Liver Diseases: Liver Meeting 2016. Boston, November 11-15, 2016. Abstract 21.

Original Article