title: Safety and efficacy of ledipasvir-sofosbuvir in black patients with hepatitis C virus infection: A retrospective analysis of phase 3 data.
abstract: Black patients chronically infected with genotype 1 hepatitis C virus (HCV) have historically had lower rates of response to interferon-based treatment than patients of other races. In the phase 3 ION program, the single-tablet regimen of the NS5A inhibitor ledipasvir and NS5B nucleotide polymerase inhibitor sofosbuvir was shown to be safe and highly effective in the general population. The aim of this study was to evaluate the safety and efficacy of ledipasvir/sofosbuvir in black patients using data from the three open-label ION clinical trials, which evaluated the safety and efficacy of 8, 12, and 24 weeks of ledipasvir/sofosbuvir with or without ribavirin for the treatment of treatment-naïve and treatment-experienced patients with genotype 1 HCV, including those with compensated cirrhosis. The primary endpoint was sustained virologic response at 12 weeks after the end of therapy (SVR12). For our analysis, rates of SVR12, treatment-emergent adverse events, and graded laboratory abnormalities were analyzed in black versus non-black patients. Of the 1949 patients evaluated, 308 (16%) were black. On average, black patients were older, had higher body mass index, were more likely to be IL28B non-CC, and had a lower serum alanine aminotransferase at baseline than non-black patients. Overall, 95% of black and 97% of non-black patients achieved SVR12. The rate of relapse was 3% in black patients as compared with 2% in non-black patients. The most common adverse events included fatigue, headache, nausea, and insomnia. The majority of adverse events occurred more frequently in the ribavirin-containing arms of the studies. No differences were observed in overall safety by race.
  
  
  CONCLUSIONS
  A once-daily dosage of ledipasvir/sofosbuvir was similarly effective in black and non-black patients with genotype 1 HCV infection. The addition of ribavirin did not appear to increase SVR12 but was associated with higher rates of adverse events.
authors.affiliation: Duke Clinical Research Institute, Durham, NC.
authors.forename: Julius M
authors.initials: JM
authors.lastname: Wilder
authors.affiliation: Miami VA Medical Center, Miami, FL.
authors.forename: Lennox J
authors.initials: LJ
authors.lastname: Jeffers
authors.affiliation: Digestive Disease Associates, Baltimore, MD.
authors.forename: Natarajan
authors.initials: N
authors.lastname: Ravendhran
authors.affiliation: Liver Institute of Virginia, Bon Secours Health System, Richmond and Newport News, VA.
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.affiliation: Fayetteville Gastroenterology Associates, Cumberland Research Associates, Fayetteville, NC.
authors.forename: John
authors.initials: J
authors.lastname: Poulos
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sulkowski
authors.affiliation: Atlanta Gastroenterology Associates, Atlanta, GA.
authors.forename: Norman
authors.initials: N
authors.lastname: Gitlin
authors.affiliation: Emory University, Atlanta, GA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Workowski
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Jenny C
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Phillip S
authors.initials: PS
authors.lastname: Pang
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: John G
authors.initials: JG
authors.lastname: McHutchison
authors.affiliation: Duke Clinical Research Institute, Durham, NC.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Muir
authors.affiliation: Howard University, Washington, DC.
authors.forename: Charles
authors.initials: C
authors.lastname: Howell
authors.affiliation: Swedish Medical Center, Seattle, WA.
authors.forename: Kris
authors.initials: K
authors.lastname: Kowdley
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: Nezam
authors.initials: N
authors.lastname: Afdhal
authors.affiliation: University of Pennsylvania School of Medicine, Philadelphia, PA.
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000009:adverse effects / Q000627:therapeutic use*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000069474:Sofosbuvir; D016896:Treatment Outcome; D014542:Uridine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C000595958:ledipasvir, sofosbuvir drug combination; D014542:Uridine Monophosphate; D000069474:Sofosbuvir