title: Adverse events associated with ribavirin in sofosbuvir-based therapies for patients with chronic hepatitis C: A community practice experience.
abstract: OBJECTIVE
  Due to high sustained virological response (SVR) rates, sofosbuvir-based regimens are currently a mainstay for hepatitis C virus (HCV) therapies. The addition of pegylated interferon (PEG-IFN) and ribavirin impacts patients' quality of life during treatment. This study aimed to compare severe adverse events (SAEs) amongst therapeutic combinations for HCV in a community clinic setting.
  
  
  METHODS
  From December 2013 to July 2014, 128 chronic HCV-infected patients were treated with sofosbuvir, ribavirin and weekly PEG-IFN for 12 weeks (cohort 1), 12 or 24 weeks of sofosbuvir and ribavirin (cohorts 2 and 3) or sofosbuvir plus simeprevir for 12 weeks (cohort 4). Adverse events were recorded from baseline to 12 or 24 weeks of treatment.
  
  
  RESULTS
  SAEs appeared in 15.6-53.8% of ribavirin-inclusive treated patients compared to 4.8% of the ribavirin-free regimen. PEG-IFN, sofosbuvir plus ribavirin had the highest frequencies of fatigue, headache and rash compared to either 12 or 24 weeks of ribavirin and sofosbuvir. However, sofosbuvir and ribavirin regimens led to significant increases in dyspnea, need for ribavirin dose reductions and withdrawal from treatment due to SAEs. Anemia was also more frequent in ribavirin-inclusive combinations (P < 0.001). Conversely, sofosbuvir plus simeprevir reached similar SVR rates at week 12 post-treatment compared to all ribavirin-containing regimens, but with significantly fewer adverse events (P = 0.006). At week 12 post-treatment, cirrhotic patients experienced a higher virological relapse rate than non-cirrhotic patients (P = 0.019).
  
  
  CONCLUSIONS
  Ribavirin-inclusive HCV therapies increased the frequencies of SAEs, had higher dropout rates and increased patient morbidity.
authors.affiliation: Liver Center, Huntington Medical Research Institutes, Pasadena.|Pfleger Liver Institute and the Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Myron John
authors.initials: MJ
authors.lastname: Tong
authors.affiliation: Liver Center, Huntington Medical Research Institutes, Pasadena.
authors.forename: Patrick Weijen
authors.initials: PW
authors.lastname: Chang
authors.affiliation: Liver Center, Huntington Medical Research Institutes, Pasadena.
authors.forename: Thatcher Thi
authors.initials: TT
authors.lastname: Huynh
authors.affiliation: Liver Center, Huntington Medical Research Institutes, Pasadena.
authors.forename: Alexander Anthony
authors.initials: AA
authors.lastname: Rosinski
authors.affiliation: Liver Center, Huntington Medical Research Institutes, Pasadena.
authors.forename: Lori Terese
authors.initials: LT
authors.lastname: Tong
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D003153:Community Health Services; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts / Q000706:statistics & numerical data; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000072230:Sustained Virologic Response; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin; D000069474:Sofosbuvir
keywords: adverse drug event; chronic hepatitis C; peginterferon; ribavirin; simeprevir; sofosbuvir