BOSTON, MA—Long-term follow-up data show that sustained virologic response (SVR) at 12 weeks achieved with daclatasvir (DCV)-based regimens are durable in patients with chronic hepatitic C virus (HCV) infection, study authors reported at The Liver Meeting® 2016.
In addition, progression of liver disease or hepatocellular carcinoma are infrequent.
To date, all-oral direct-acting antiviral (DAA) regimens of DCV, a pangenotypic NS5A inhibitor, in combination with sofosbuvir (DCV + SOF) or asunaprevir (DCV + ASV) have achieved high rates of SVR in diverse populations with HCV.
“This observational study sought to evaluate long-term efficacy and safety, and to characterize hepatic disease progression, in chronic HCV patients treated in Phase 2 or 3 clinical studies with DCV-based regimens,” noted K. Rajender Reddy, MD, director of hepatology at the University of Pennsylvania, Philadelphia, PA.
The ongoing long-term follow-up study, AI444-046, enrolled 1503 patients from 21 clinical studies with a data cut-off of October 13, 2015. Patients are being monitored for 3 years’ posttreatment. The parent studies included treatment with DCV + SOF ± ribavirin (RBV; n=237); DCV + ASV (n=389); DCV + ASV + beclabuvir (BCV) ± RBV (n=267), DCV + pegylated interferon (pegIFN)/RBV (n=199); or DCV + ASV + pegIFN/RBV (n=411).
Eligible patients were enrolled within 6 months of finishing the parent study and were evaluated yearly to twice yearly for HCV RNA levels, hepatic disease progression, decompensation events, and persistence of NS5A and NS3 resistance variants.
Most patients were male (60%) and had HCV genotype (GT) 1a (42%) or 1b (45%). More patients were treated with DAA-only regimens (59%) compared with those that contained IFN (41%). Among the patients enrolled with cirrhosis (18%), more were treated with DAA-only regimens (20%) than IFN-containing regimens (14%).
The study noted that 6% of SVR12 responders (85 of 1329 patients) and 44% of non-responders (70 of 160 patients) failed to complete long-term follow-up. Median duration of long-term follow-up for all patients was 111 weeks from parent study to Week 12 and 123 weeks from parent study to end of treatment.
Overall, 1329 of 1489 evaluable patients achieved SVR12 in the parent studies, of which 1,316 (99%) achieved SVR at their most recent long-term follow-up visit. This included 838 of 842 (>99%) of those treated with DAA-only regimens and 478/487 (98%) treated with IFN-containing regimens.
Twelve of the SVR12 responders relapsed after achieving SVR12, 9 on or before and 3 after the parent study follow-up Week 24. One SVR12 responder treated with DCV + ASV + BCV ± RBV for HCV GT 1a infection was reinfected with GT3 at follow-up Week 48.
Generally, relapses after SVR12 were less common after receiving an all-oral regimen (0.4%) vs. receiving a pegIFN-based regimen (2%).
“Hepatic disease progression (1%) or new HCC (2%) was infrequent, and there were no diagnoses of HCC recurrence,” they noted.
No serious adverse events or the 11 deaths were considered to be treatment-related.
“Among non-responders, emergent NS5A and NS3 substitutions were replaced by wild-type sequences in 27 of 157 (17%) and 3 of 47 (71%) patients, respectively,” noted Dr. Reddy.
Dr. Reddy added that additional monitoring in patients treated with DCV-containing regimens is ongoing.