Three more impressive hepatitis C (HCV) studies have been published (in print):
- NEJM 2014; 370: 1973-82
- NEJM 2014; 370: 1983-92
- NEJM 2014; 370: 1993-2001
In the commentary on these three studies (pages 2043-47), the authors note that only a year ago, they had “speculated that highly effective interferon-free regimens would be available and should revolutionize the treatment of HCV infection…Now, we would have to say that the future is here.”
In the first study, “TURQUOISE-II,” 380 patients with Child-Pugh class A cirrhosis received either 12 weeks or 24 weeks of ritonavir (ABT-450/r), ombitasvir (ABT-267), dasabuvir (ABT-333) and ribavirin. In the 12 week group, the sustained virologic response (SVR) was 91.8% whereas the 24 week group had an SVR of 95.9%.
In the second study, “PEARL-III and PEARL-IV,” 419 patients with genotype Ib and 305 patients with genotype 1a received 12 weeks of ritonavir, ombitasvir, dasavuvir, and ribavirin (or placebo) for 12 weeks. For genotype 1b, SVR were 99.5% with ribavirin and 99% without ribavirin. For genotype 1a, SVR were 97% and 90.2% respectively.
In the third study, “VALENCE,” among 419 patients with genotype 2 or 3 (21% with cirrhosis, and 58% previous interferon-based treatment), patients were treated with sofusbuvir-ribavirin or placebo for 12 weeks; the genotype 3 patients treatment was extended to 24 weeks (unblinded) after data emerged indicating a need for longer treatment course. For the genotype 2 patients, SVR was met in 93%. For genotype 3 patients, 85% who received a 24 week course had an SVR.
Key Points (from editorial):
- In the first two studies, SVR was approximately 96% in untreated and treated patients without cirrhosis.
- Patients with cirrhosis had a response rate of approximately 90%.
- Ethnicity, IL28B, and baseline HCV RNA were not important factors in predicting response.
- “In the era of potent DAA (direct-acting antivirals), …response-guided therapy is no longer necessary” because by week 4 of treatment, 99% of patients had non-quantifiable HCV RNA.
- Drug resistance against these DAAs is common in preclinical studies; therefore, combination regimens are important. “In the case of sofosbuvir and ledipasvir, a two-drug combination is sufficient…Sofosbuvir seems to have a high genetic barrier to resistance.”
- “Perhaps the more important achievement of these interferon-free regimens is the lower rate and severity of side effects.”
Related (recent) blog posts:
gutsandgrowth 