title: A randomized, controlled study of peginterferon lambda-1a/ribavirin ± daclatasvir for hepatitis C virus genotype 2 or 3.
abstract: OBJECTIVE
  Peginterferon Lambda was being developed as an alternative to alfa interferon for the treatment of chronic hepatitis C virus (HCV) infection. We compared peginterferon Lambda-1a plus ribavirin (Lambda/RBV) and Lambda/RBV plus daclatasvir (DCV; pangenotypic NS5A inhibitor) with peginterferon alfa-2a plus RBV (alfa/RBV) in treatment-naive patients with HCV genotype 2 or 3 infection.
  
  
  METHODS
  In this multicenter, double-blind, phase 3 randomized controlled trial, patients were assigned 2:2:1 to receive 24 weeks of Lambda/RBV, 12 weeks of Lambda/RBV + DCV, or 24 weeks of alfa/RBV. The primary outcome measure was sustained virologic response at post-treatment Week 12 (SVR12).
  
  
  RESULTS
  Overall, 874 patients were treated: Lambda/RBV, n = 353; Lambda/RBV + DCV, n = 349; alfa/RBV, n = 172. Patients were 65 % white and 33 % Asian, 57 % male, with a mean age of 47 years; 52 % were infected with genotype 2 (6 % cirrhotic) and 48 % with genotype 3 (9 % cirrhotic). In the Lambda/RBV + DCV group, 83 % (95 % confidence interval [CI] 78.5, 86.5) achieved SVR12 (90 % genotype 2, 75 % genotype 3) whereas SVR12 was achieved by 68 % (95 % CI 63.1, 72.9) with Lambda/RBV (72 % genotype 2, 64 % genotype 3) and 73 % (95 % CI 66.6, 79.9) with peginterferon alfa/RBV (74 % genotype 2, 73 % genotype 3). Lambda/RBV + DCV was associated with lower incidences of flu-like symptoms, hematological abnormalities, and discontinuations due to adverse events compared with alfa/RBV.
  
  
  CONCLUSIONS
  The 12-week regimen of Lambda/RBV + DCV was superior to peginterferon alfa/RBV in the combined population of treatment-naive patients with genotype 2 or 3 infection, with an improved tolerability and safety profile compared with alfa/RBV.
authors: Department of Hepatology, Queen Mary University of London, 4 Newark Street, London, UK.
authors: Graham R
authors: GR
authors: Foster
authors: Department of Gastroenterology and Nutrition, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima-shi, Hiroshima, Japan.
authors: Kazuaki
authors: K
authors: Chayama
authors: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung, Taiwan.
authors: Wan-Long
authors: WL
authors: Chuang
authors: Liver Unit, Hospital F. J. Muñiz, Uspallata 2272, Buenos Aires, Argentina.
authors: Hugo
authors: H
authors: Fainboim
authors: Helsinki University and Clinic of Gastroenterology, University of Helsinki, Haartmaninkatu 4, Helsinki, Finland.
authors: Martti
authors: M
authors: Farkkila
authors: Liver Unit, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
authors: Adrian
authors: A
authors: Gadano
authors: Internal and Specialistic Medicine, Viral Hepatitis Unit, Second University of Naples, Via Pansini 5 Bld.3, 08131 Naples, Italy.
authors: Giovanni B
authors: GB
authors: Gaeta
authors: Hepatology, Henri Mondor Hospital, AP-HP, INSERM U955, University Paris-Est, 51 av du Maréchal de Lattre de Tassigny, Créteil, France.
authors: Christophe
authors: C
authors: Hézode
authors: Center for Digestive and Liver Diseases, Miyazaki Medical Center Hospital, 2-16 Takamtsu-cho, Miyazaki-shi, Miyazaki, Japan.
authors: Yukiko
authors: Y
authors: Inada
authors: Department of Internal Medicine, Pusan National University and Medical Research Institute, College of Medicine, Pusan National University Hospital, 179 Gudeok-Ro, Seo-gu, Pusan, Republic of Korea.
authors: Jeong
authors: J
authors: Heo
authors: Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, Japan.
authors: Hiromitsu
authors: H
authors: Kumada
authors: Section of Hepatology, Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Taoei Road, Niaosung District, Kaohsiung, 833 Taiwan.
authors: Sheng-Nan
authors: SN
authors: Lu
authors: Hepatology, Hôpital Beaujon, 100 Bd du Général Leclerc, 92110 Clichy, France.
authors: Patrick
authors: P
authors: Marcellin
authors: Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Hôpital Erasme, Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium.
authors: Christophe
authors: C
authors: Moreno
authors: Gastroenterology, Alfred Hospital, 99 Commercial Road, Melbourne, Australia ; Department of Medicine, Monash University, Melbourne, Australia.
authors: Stuart K
authors: SK
authors: Roberts
authors: AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, Sydney, NSW 20150 Australia.
authors: Simone I
authors: SI
authors: Strasser
authors: Department of Gastroenterology, St. Vincent's Hospital and the University of Melbourne, SVHM Level 4 Daly Wing, 35 Victoria Pde, PO Box 29000, Fitzroy, Australia.
authors: Alexander J
authors: AJ
authors: Thompson
authors: Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8-5, Chuo-ku, Sapporo, Japan.
authors: Joji
authors: J
authors: Toyota
authors: Department of Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, Republic of Korea.
authors: Seung Woon
authors: SW
authors: Paik
authors: Baylor Liver Health, Baylor College of Medicine, 6620 Main Street, Suite 1425, Houston, TX USA.
authors: John M
authors: JM
authors: Vierling
authors: Department of Experimental and Clinical Medicine, MASVE Center, Universita Di Firenze, Largo Brambilia, 3, 50134 Florence, Italy.
authors: Anna L
authors: AL
authors: Zignego
authors: Bristol-Myers Squibb Global Biometric Sciences, 5 Research Parkway, Wallingford, CT USA.
authors: David
authors: D
authors: Cohen
authors: Discovery Virology, Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT USA.
authors: Fiona
authors: F
authors: McPhee
authors: Exploratory Clinical and Translational Research, Bristol-Myers Squibb Company, Princeton, NJ USA.
authors: Megan
authors: M
authors: Wind-Rotolo
authors: Global Clinical Research, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492 USA.
authors: Subasree
authors: S
authors: Srinivasan
authors: Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb Company, Hopewell, NJ USA.
authors: Matthew
authors: M
authors: Hruska
authors: Analytical and Bioanalytical Development, Bristol Myers Squibb Company, Princeton, NJ USA.
authors: Heather
authors: H
authors: Myler
authors: Global Clinical Research, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492 USA ; Shionogi Inc., 300 Campus Drive, Florham Park, NJ 07932 USA.
authors: Simon D
authors: SD
authors: Portsmouth
keywords: Genotype 2; Genotype 3; Hepatitis C virus; Peginterferon alfa-2a; Peginterferon lambda-1a