Lower response to simeprevir and sofosbuvir in HCV genotype 1 in routine practice compared with clinical trials

Abstract

BackgroundHigh sustained virological response at 12 weeks after end of treatment (SVR12) with 12 weeks of simeprevir and sofosbuvir±ribavirin (SMV+SOF±RBV) has been demonstrated in hepatitis C virus genotype 1 (HCV-1) but is based on limited data. Therefore, we performed a meta-analysis of available data evaluating the effectiveness of SMV+SOF±RBV in HCV-1.MethodsWe performed a comprehensive literature search in June 2015 to identify randomised controlled trials (RCTs) and observational studies of HCV-1 patients treated with 12 weeks of SMV+SOF±RBV. Original studies with SVR12 data in ≥5 HCV-1 patients were included. We excluded studies on liver transplant recipients and/or patients co-infected with HIV or hepatitis B/D. We estimated pooled effect sizes using a random-effects model and evaluated heterogeneity with Cochrane Q-test, p≤0.10 and I2 statistic ≥50%.ResultsPooled SVR12 was 85.6% (CI 81.3% to 89.0%) in 1389 HCV-1 patients from 15 studies. On subgroup analysis, SVR12 was 83.9% (CI 79.4% to 87.5%) in observational studies, which was lower than 93.5% (CI 85.7% to 97.2%) in RCTs. A trend showed SVR12 was higher in mild fibrosis, 93.0% (CI 86.2% to 96.6%) compared with advanced fibrosis, 81.5% (CI 75.7% to 86.1%), OR 2.22 (CI 0.79 to 6.25, p=0.131). There was no significant difference in SVR12 rates between HCV-1a, 89.9% (CI 81.9% to 94.6%) and HCV-1b, 89.0% (CI 78.9% to 94.6%) with OR 1.35 (CI 0.75 to 2.42, p=0.322). The most common pooled side effects were: headache 15.2% (n=55/361), fatigue 12.1% (n=78/646), nausea 9.5% (n=50/527) and rash 9.3% (n=68/728).ConclusionsSMV+SOF±RBV is an effective regimen in HCV-1 patients. The SVR12 rate in observational studies was lower than that in RCTs, which may reflect the more diverse patient population in real-world settings.

Efficacy and safety of sofosbuvir plus simeprevir therapy in Egyptian patients with chronic hepatitis C: a real-world experience

“…In another subgroup analysis of patients with SVR12 and fibrosis data, there was a higher SVR12 rate in patients with mild fibrosis (93%) compared with those with advanced fibrosis (82%), with a trend favouring SVR12 in patients with mild fibrosis 6 14…”

Effectiveness and safety of daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: Systematic review and meta‐analysis

“…37 Importantly, in this study, the interferon-free and RBV-free regimen of DCV + ASV provided SVR rate in genotype 1b infection that was slightly higher than that of a pooled analysis reported for combinations of SOF plus simeprevir with or without RBV in HCV patients with genotype 1b infection, with similar frequencies of most common AEs. 38 Therefore, on the basis of its favorable safety and high response rates with good tolerability in ineligible/intolerant and nonresponder patients with compensated cirrhosis, irrespectively of gender, race, advanced age, and non-CC IL28B genotype, DCV + ASV is a promising treatment option for this patient population, especially when genotype 1b is highly prevalent.…”

Urgency to treat patients with chronic hepatitis C in Asia

“…In a large, real‐world observational cohort study ( N = 4365) of SOF/LDV ± RBV in HCV GT1 infection, SVR rates of 93.2% and 96.6% were reported after 8 and 12 weeks of treatment, respectively, in non‐cirrhotic treatment‐naive patients with baseline HCV RNA <6 × 10 6 IU/mL who received SOF/LDV . A recent meta‐analysis of clinical trials and real‐world observational studies evaluating the effectiveness of SMV + SOF ± RBV in patients with HCV GT1 found that SVR rates reported in observational studies were lower (84%) than those reported in randomized controlled trials (RCTs;94%) with this regimen . The French Observational Cohort ANRS CO22 HEPATHER study is designed to follow up to 15 000 HCV patients over 10 years to collect real‐world clinical data.…”

“…These findings extend to challenging patient populations, with SVR rates of 95.5% reported in chronic hemodialysis patients infected with HCV GT1 receiving DCV + ASV in another recent prospective observational study in Japan . Yet, despite these positive findings, there are relatively few real‐world studies of DAAs—particularly in Asia—and insufficient data to draw robust comparisons of real‐world and clinical trial outcomes in different patient subgroups (e.g., treatment‐naive and experienced patients, or cirrhotic and non‐cirrhotic patients) …”

“…51 A recent meta-analysis of clinical trials and real-world observational studies evaluating the effectiveness of SMV + SOF AE RBV in patients with HCV GT1 found that SVR rates reported in observational studies were lower (84%) than those reported in randomized controlled trials (RCTs;94%) with this regimen. 71 The French Observational Cohort ANRS CO22 HEPATHER study is designed to follow up to 15 000 HCV patients over 10 years to collect real-world clinical data. Initial data from the cohort, which includes patients with HCV GT1 who received treatment with SOF + DCV for 12 or 24 weeks (N = 317), showed that SVR12 rates were higher after 24 weeks (93.4%) than 12 weeks of treatment (84.9%).…”