Daclatasvir plus sofosbuvir, with or without ribavirin, for hepatitis C virus genotype 3 in a French early access programme.
Optimally effective treatment for hepatitis C virus genotype 3 (GT3) is urgently needed, particularly in advanced liver disease. Daclatasvir plus sofosbuvir was efficacious in phase 3 studies. Real-world data for daclatasvir+sofosbuvir in advanced GT3 infection are presented from the French Temporary Authorisation for Use programme, which allowed patients in need without other treatment options access to daclatasvir ahead of its market authorization.



Patients with F3/F4 fibrosis and/or extrahepatic hepatitis C virus manifestations, post-liver transplant hepatitis C virus recurrence and/or indication for liver/kidney transplant, were treated with daclatasvir+sofosbuvir (60+400 mg daily) for a recommended duration of 24 weeks. Addition of ribavirin and/or shorter treatment was at physician's discretion. The primary efficacy analysis was sustained virological response at post-treatment week 12 (SVR12; modified intention-to-treat). Safety was assessed by spontaneous adverse event reporting.



The efficacy population comprised 333 patients, mostly cirrhotic (77%, of whom 18% were decompensated) and treatment experienced (72%). After 24 weeks of daclatasvir+sofosbuvir, SVR12 was 89% (174/196) overall (95% CI 83.6-92.5%), 98% (43/44) without cirrhosis (95% CI 88.2-99.6%) and 86% (129/150) with any degree of cirrhosis (95% CI 79.5-90.7%), without SVR12 increase in those who received additional ribavirin for 24 weeks (SVR12 82% [50/61; 95% CI 70.5-89.6%]). Among 516 GT3-infected patients with safety data, 5 discontinued for adverse events and 11 died.



Daclatasvir+sofosbuvir achieved high SVR12 rates and was well tolerated in this large real-world cohort of GT3-infected patients with advanced liver disease, without benefit of ribavirin in those treated 24 weeks.
Service d'Hépatologie, CHU Henri-Mondor, AP-HP, Université Paris-Est, INSERM U955, Créteil, France.
Christophe
0000-0002-6762-8033
C
Hézode
Service d'Hépato-Gastroentérologie et de Transplantation Hépatique, Hôpital Pitié-Salpêtrière, Paris, France.
Pascal
P
Lebray
Centre d'Investigation de la Fibrose Hépatique, Hôpital Haut-Lévêque, CHU de Bordeaux, Pessac, France.
Victor
V
De Ledinghen
Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France.
Fabien
F
Zoulim
Service d'Hépatologie et de Soins Intensifs Digestifs, CHRU Jean Minjoz, Besançon Cedex, France.
Vincent
V
Di Martino
AP-HP, Hôpital Beaujon, Service d'Hépatologie, Clichy, France.
Nathalie
N
Boyer
Hépato-Gastroentérologie, CHU de Montpellier, Hôpital Saint-Eloi, Montpellier, France.
Dominique
D
Larrey
Service d'Hépato-Gastroentérologie, CHU Timone Marseille, Aix Marseille Université, Marseille, France.
Danielle
D
Botta-Fridlund
Service d'Hépato-Gastroentérologie et d'Assistance Nutritive, Laboratoire Inflammation Tissus Epithéliaux et Cytokines EA 4331, CHU Poitiers, Poitiers Cedex, France.
Christine
C
Silvain
Hepatology Unit, Hôpital Cochin, AP-HP, Université Paris-René Descartes, INSERM U-181 and USM20, Pasteur Institute U1223, Paris, France.
Hélène
H
Fontaine
CHU Trousseau, Tours, France.
Louis
L
D'Alteroche
CHU de Grenoble, Clinique Universitaire d'Hépato-Gastroentérologie, Grenoble, France.
Vincent
V
Leroy
Hôpital Saint-Joseph, Marseille, France.
Marc
M
Bourliere
Service d'Hépato-Gastroentérologie, CHU Angers, Angers, France.
Isabelle
I
Hubert-Fouchard
Service des Maladies du Foie, CHU Rennes, Rennes, France.
Dominique
D
Guyader
Centre Hospitalier Intercommunal, Créteil, France.
Isabelle
I
Rosa
Service d'Hépato-Gastroentérologie, CHU Amiens Nord, Amiens, France.
Eric
E
Nguyen-Khac
Bristol-Myers Squibb R&D, Rueil-Malmaison, Paris, France.
Larysa
L
Fedchuk
Bristol-Myers Squibb R&D, Rueil-Malmaison, Paris, France.
Raoudha
R
Akremi
Bristol-Myers Squibb R&D, Rueil-Malmaison, Paris, France.
Yacia
Y
Bennai
Bristol-Myers Squibb R&D, Rueil-Malmaison, Paris, France.
Anne
A
Filipovics
Bristol-Myers Squibb R&D, Princeton, NJ, USA.
Yue
Y
Zhao
INSERM U954, CHU de Nancy and Université de Lorraine, Vandoeuvre-lès-Nancy, France.
Jean-Pierre
JP
Bronowicki
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002219:Carbamates; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005602:France; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008103:Liver Cirrhosis / Q000821:virology*; D016031:Liver Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012008:Recurrence; D012254:Ribavirin / Q000008:administration & dosage; D000069474:Sofosbuvir / Q000008:administration & dosage*; D000072230:Sustained Virologic Response; D014633:Valine / Q000031:analogs & derivatives
D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D012254:Ribavirin; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir
compassionate use; daclatasvir; genotype 3; hepatitis C; real-world data; sofosbuvir