title: 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: OBJECTIVE
  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/m(2), 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/m(2)) was the only factor that correlated with post-treatment relapse by multivariate analysis.
authors.affiliation: Liver Center, Queen's Medical Center, Honolulu, HI, USA.|Department of Medicine, John A. Burns School of Medicine, Honolulu, HI, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Roytman
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, Honolulu, HI, USA. resham@hawaii.edu.|, 550 S Beretania Street, Suite 405, Honolulu, HI, 96813, USA. resham@hawaii.edu.
authors.forename: Resham
authors.initials: R
authors.lastname: Ramkissoon
authors.affiliation: Department of Medicine, John A. Burns School of Medicine, Honolulu, HI, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Wu
authors.affiliation: Liver Center, Queen's Medical Center, Honolulu, HI, USA.
authors.forename: Leena
authors.initials: L
authors.lastname: Hong
authors.affiliation: Liver Center, Queen's Medical Center, Honolulu, HI, USA.
authors.forename: Ruby
authors.initials: R
authors.lastname: Trujillo
authors.affiliation: Liver Center, Queen's Medical Center, Honolulu, HI, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Huddleston
authors.affiliation: Liver Center, Queen's Medical Center, Honolulu, HI, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Poerzgen
authors.affiliation: Liver Center, Queen's Medical Center, Honolulu, HI, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Seto
authors.affiliation: Liver Center, Queen's Medical Center, Honolulu, HI, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Wong
authors.affiliation: Liver Center, Queen's Medical Center, Honolulu, HI, USA.|Department of Medicine, John A. Burns School of Medicine, Honolulu, HI, USA.
authors.forename: Naoky
authors.initials: N
authors.lastname: Tsai
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D044466:Asian People; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004333:Drug Administration Routes; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000208:ethnology / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage*; D000069616:Simeprevir / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin; D000069616:Simeprevir
keywords: Decompensated cirrhosis; East-Asian; Hepatitis C; Simeprevir + sofosbuvir; Treatment