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Real-world responses to HCV treatment among US veterans match best clinical trial results
Keith Alcorn, 2016-11-14 02:20:00
Direct-acting antiviral treatment is curing people of hepatitis C infection in clinics at similar rates to those seen in clinical trials, and there don’t seem to be major differences between drug regimens, according to results of a large population study presented at the 2016 Liver Meeting in Boston this weekend.
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 up 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 US Veterans Affairs’ clinics – finds that patients receiving DAA treatment in those hospitals are being cured at 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 recommended for treatment reported sustained virologic response (SVR12) rates above 90% for genotype 1, around 75% for genotype 3, and somewhat lower for each genotype in cases where people had 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 experience of treatment who have a viral load below 6 million IU/ml.
The study population comprised 17,487 HCV-infected patients who started therapy with direct-acting antiviral agents without interferon between January 2014 and June 2015 at 167 VA medical centres in the United States . Follow-up was to April 2016. The main study outcome was sustained virological response (SVR). This was analysed 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 (SOF)/ribavirin: n = 2986
- Ledipasvir/sofosbuvir (LDV/SOF): n = 11,327
- Paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD): n = 3174.
The study measured sustained virologic response rates 12 weeks after completion of treatment (SVR12). If SVR12 data were missing, the SVR12 result was imputed from SVR4 measurements (5.7% of cases).
|
% treated |
SVR 12% |
|
|
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 genotype 1 infection there was little difference in SVR12 between those with or without cirrhosis (90.6% vs 93.6%), virologic 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, and 77.5% vs 69.2% for genotype 3).
The study also looked at treatment outcomes in 1975 patients who qualified for a n 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 infection, and among those with genotype 2 or 3 infection, treatment experience. Male sex, black or Hispanic ethnicity, diabetes, low platelet count, low serum albumin and elevated bilirubin all independently predicted failure to achieve SVR, as did cirrhosis.
Source:1
