Examining the clinical course of genotype 1 chronic hepatitis C patients treated with the cosmos regimen: including patients with advanced liver disease and East Asian ancestry

Abstract

Background/objectives The COSMOS study was a phase 2a clinical trial that showed high cure rates of genotype 1 chronic hepatitis C (CHC) and a favorable side effect profile using a 12-week regimen of simeprevir + sofosbuvir (SIM + SOF). Given the small number of patients treated with the SIM + SOF regimen in the COSMOS trial, there is uncertainty regarding the efficacy and safety of this combination therapy. We now report our experience with the COSMOS regimen in the multiethnic population of Hawaii, including patients of East Asian ancestry and with decompensated cirrhosis. Methods This study is a retrospective review of 138 patients treated with a fixed dose regimen of SIM 150 mg and SOF 400 mg daily at a single referral center. We collected data on demographics, side effects, laboratory studies and sustained virological response (SVR). Statistical analysis was performed with Stata v8.2 software. Results Baseline characteristics of the 138 patients initiated with SIM + SOF therapy were: 68.8 % cirrhotic (22.1 % of those Child-Pugh Class B), 37 % Asian, 11.6 % Pacific Islander, 63 % male, mean age 61.3 ± 7.8 years, mean BMI 27.8 ± 6.1 kg/m2, 26.8 % diabetic, 63.8 % genotype 1a, 44.9 % previously treatment experienced. A total of 100 % of patients that completed therapy (n = 137) had undetectable viral loads at end of treatment (EOT). Twelve patients relapsed post-treatment resulting in an overall 12 week SVR (SVR12) rate of 89.1 %. 95 % of decompensated cirrhotic patients achieved SVR12, compared to 85.3 % of compensated cirrhotic patients and 93 % of non-cirrhotic patients. 92 % of Asian patients achieved SVR12 compared to 87.5 % in non-Asian patients. There were no statistically significant differences in SVR12 between treatment naive and treatment experienced patients (86.8 vs 91.9 %). 87.5 % of post-transplant patients achieved SVR12. The main side effects were headache 16.2 %, fatigue 24.2 %, pruritis 14.1 %; none were >grade 2 in severity. There were no differences in side effect profiles of patients with decompensated cirrhosis. Pruritis only was statistically significant between Asians and non-Asians (22 vs 5.7 %). Trends toward improvement in platelet counts and total bilirubin were noted at 12-weeks post treatment, while improvement in albumin in cirrhotic patients reached statistical significance (3.77–4.01 mg/dL, p = 0.0108). Conclusions The 12-week fixed dose course of SIM + SOF was well tolerated in a multiethnic population of primarily cirrhotic patients, including those with decompensated disease. This real world trial achieved SVR12 rates comparable to the COSMOS data. Higher incidence of adverse side effects was not observed with an exception of higher rate of pruritis in Asians. The increase in albumin in cirrhotic patients was statistically significant and suggested early improvement in synthetic function following viral eradication. Higher BMI (≥30 kg/m2) was the only factor that correlated with post-treatment relapse by multivariate analysis.

Real-world experience with interferon-free, direct acting antiviral therapies in Asian Americans with chronic hepatitis C and advanced liver disease

“…[ 36 ] The effect of cirrhosis on response to DAAs was also evaluated in a retrospective study from Hawaii that included a significant proportion of Asian patients with HCV-1 (51 Asians and 87 non-Asians) and reported lower rates of SVR12 following 12 weeks of SMV/SOF in patients with cirrhosis than those without cirrhosis (85% vs 93%), but this was not statistically significant, and the authors did not report the effect of cirrhosis in Asians versus non-Asians. [ 37 ] In contrast, recent clinical trials on IFN-free DAA regimens from Asia (SOF/RBV, LDV/SOF ± RBV, and daclatasvir/asunaprevir) reported that cirrhosis had no effect on SVR12; rates of SVR were high regardless of cirrhosis (93–100%). [ 32 – 34 , 38 – 40 ] However, the proportion of patients with cirrhosis was low in most studies (10–22%), and all were compensated, as compared to our study, in which 50% of patients had cirrhosis, and most (67%) had were decompensated.…”

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

“… 10 24 Thirteen were observational studies: seven were prospective 16–20 22 23 and six were retrospective. 14 15 21 25–27 Mean age ranged from 58 to 63 years. Most patients were male (53–81%).…”

“…Five studies 10 18 19 21 25 provided SVR12 data on a total of 343 patients with mild fibrosis. The pooled rate of SVR12 was 93.0% (CI 86.2% to 96.6%).…”

“…Nine studies 10 14 18 20 21 24–27 provided SVR12 data on a total of 711 patients with advanced fibrosis. These studies used different definitions to classify patients with advanced fibrosis; seven defined advanced fibrosis as presence of cirrhosis 14 18 20 21 25–27 while two used the METAVIR scoring system. 10 24 The pooled rate of SVR12 was 81.5% (CI 75.7% to 86.1%) for patients with advanced fibrosis.…”

“…In our subgroup analysis of patients with SVR12 and fibrosis data, we observed 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, OR 2.22 (95% CI 0.79 to 6.25, p=0.131). Of the nine studies with SVR12 data on patients with advanced fibrosis, both RCTs 10 24 had SVR12 rates greater than 90% while the seven observational studies 14 18 20 21 25–27 had lower SVR12 rates ranging from 68.4% to 88.9%. This finding is likely due to the diversity of real-world patients with more variability in terms of medication adherence, follow-up and comorbidities, compared with the highly selective patients included in clinical trials.…”