title: Real-world effectiveness for 12 weeks of ledipasvir-sofosbuvir for genotype 1 hepatitis C: the Trio Health study.
abstract: Early data regarding the "real-world" experience with novel therapies for hepatitis C (HCV) are encouraging. Data are still limited, however, regarding real-world rates of sustained virologic response (SVR) for ledipasvir-sofosbuvir (LDV-SOF), particularly for patients with prior treatment failure. We performed a retrospective cohort study of 1597 patients with chronic genotype 1 HCV who were treated using 12 weeks of the following regimens LDV-SOF±ribavirin (RBV) (n=1521 without RBV, n=76 with RBV). The primary outcome was SVR-determined at 12 weeks in an intention-to-treat design. Prescription according to Food and Drug Administration (FDA) approved labelling (adding RBV for patients with cirrhosis and treatment failure) was assessed in multivariate models. The study population was aged 60 years on average (range 19-89), 60% male, 50% Caucasian, 43% cared for at an academic centre and 30% cirrhotic. Overall, LDV-SOF resulted in a 94% SVR rate. Only 44 (2.9%) patients relapsed. LDV-SOF+RBV yielded SVR in 97% with 0 viral relapses. While cirrhosis and thrombocytopenia were associated with lower odds of SVR, in a multivariable regression model, only treatment at an academic centre and prescriptions contrary to FDA labelling were significantly associated with lower SVR-odds ratios, 0.56 95% CI (0.35-0.87) and 0.29 95% CI(0.12-0.68), respectively. The real-world experience with LDV-SOF mirrors the SVR rates observed in clinical trials. Efforts to promote prescription within FDA recommendations are warranted.
authors.affiliation: Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Tapper
authors.affiliation: Division of Gastroenterology/Hepatology, Saint Louis University School of Medicine, Saint Louis, MO, USA.
authors.forename: B R
authors.initials: BR
authors.lastname: Bacon
authors.affiliation: Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Curry
authors.affiliation: Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Dieterich
authors.affiliation: Division of Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Flamm
authors.affiliation: Trio Health Analytics, La Jolla, CA, USA.
authors.forename: L E
authors.initials: LE
authors.lastname: Guest
authors.affiliation: Liver Care Network, Swedish Medical Center, Seattle, WA, USA.
authors.forename: K V
authors.initials: KV
authors.lastname: Kowdley
authors.affiliation: Trio Health Analytics, La Jolla, CA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Lee
authors.affiliation: The Liver Center, Queen's Medical Center, Honolulu, HI, USA.
authors.forename: N C
authors.initials: NC
authors.lastname: Tsai
authors.affiliation: Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA.
authors.forename: Z M
authors.initials: ZM
authors.lastname: Younossi
authors.affiliation: Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: N H
authors.initials: NH
authors.lastname: Afdhal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use; D000069474:Sofosbuvir; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D014542:Uridine Monophosphate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C000595958:ledipasvir, sofosbuvir drug combination; D012254:Ribavirin; D014542:Uridine Monophosphate; D000069474:Sofosbuvir
keywords: cirrhosis; ledipasvir; liver disease; ribavirin; sofosbuvir