Michael Manns1, Stefan Zeuzem2, Ajit Sood3, Yoav Lurie4, Markus Cornberg5, Hartwig Klinker6, Peter Buggisch7, Martin Rössle8, Holger Hinrichsen9, Ismail Merican10, Yaron Ilan11, Stefan Mauss12, Saif Abu-Mouch13, Andryes Horban14, Thomas H Müller15, Christoph Welsch2, Rongdean Chen16, Rab Faruqi16, Lisa D Pedicone16, Heiner Wedemeyer5. 1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. Electronic address: manns.michael@mh-hannover.de. 2. Department of Medicine I, J.W. Goethe University Hospital, Frankfurt, Germany. 3. Dayanand Medical College and Hospital, Ludhiana, Punjab, India. 4. Gastroenterology and Hepatology, Sourasky Medical Center, Tel Aviv, Israel. 5. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany. 6. Division of Infectious Diseases, Department of Internal Medicine II, University of Wurzburg Medical Center, Wurzburg, Germany. 7. Liver Center Hamburg, IFI-Institute, Hamburg, Germany. 8. Center for Ambulatory Gastroenterology and Endocrinology, Freiburg, Germany. 9. Practice for Gastroenterology and Hepatology, Kiel, Germany. 10. Selayang Hospital, Selangor, Malaysia. 11. Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel. 12. Center for HIV and Hepatogastroenterology, Dusseldorf, Germany. 13. Hillel-yaffe Medical Center, Hadera, Israel. 14. Warsaw Medical University & Hospital of Infectious Diseases, Warsaw, Poland. 15. Institute for Medical Informatics, Biometry and Epidemiology, University of Munich, Munich, Germany. 16. Schering-Plough Corporation, Now Merck & Co., Inc., Whitehouse Station, NJ, USA.
Abstract
BACKGROUND & AIMS: There is increasing interest in identifying patients with chronic hepatitis C genotype 2 or 3 infection in whom it is possible to lower the burden of therapy while retaining high levels of efficacy. METHODS:Treatment-naive patients with chronic hepatitis C genotype 2/3 infection were randomized to receive peginterferon alfa-2b (1.5μg/kg/wk) for 24weeks (group A); peginterferon alfa-2b (1.0μg/kg/wk) for 24weeks (group B); or peginterferon alfa-2b (1.5μg/kg/wk) for 16weeks (group C), each in combination with weight-based ribavirin (800-1200mg/d). The study population comprised two cohorts: the Hep-Net cohort enrolled in Germany and an International cohort enrolled at study sites throughout Europe and Asia. The primary end point was sustained virological response (SVR). RESULTS: The study included 682 patients; 80.2% had genotype 3 infection. In the intent-to-treat population, SVR rates were 66.5%, 64.3%, and 56.6% in groups A, B, and C, and were similar in Asian and white patients. Treatment differences (A vs. B and A vs. C) failed to reach the predefined margin for noninferiority of -10%; and thus groups B and C failed to show noninferiority relative to group A. Among patients with undetectable HCV RNA at week 4, SVR rates were 75.3%, 75.9%, and 72.4%, respectively. Relapse rates were 17.8%, 16.3%, and 29.3%, respectively. Treatment-emergent serious adverse events were highest in group A and lowest in group C, and adverse events leading to discontinuation were similar across treatment arms. CONCLUSIONS: For patients with chronic hepatitis C genotype 2/3 infection, 24weeks ofpeginterferon alfa-2b (1.5μg/kg/wk) plus weight-based ribavirin remains a standard-of-care therapy; however, treatment for 16weeks may be considered for patients with undetectable HCV RNA at week 4 of the treatment.
RCT Entities:
BACKGROUND & AIMS: There is increasing interest in identifying patients with chronic hepatitis C genotype 2 or 3 infection in whom it is possible to lower the burden of therapy while retaining high levels of efficacy. METHODS: Treatment-naive patients with chronic hepatitis C genotype 2/3 infection were randomized to receive peginterferon alfa-2b (1.5μg/kg/wk) for 24weeks (group A); peginterferon alfa-2b (1.0μg/kg/wk) for 24weeks (group B); or peginterferon alfa-2b (1.5μg/kg/wk) for 16weeks (group C), each in combination with weight-based ribavirin (800-1200mg/d). The study population comprised two cohorts: the Hep-Net cohort enrolled in Germany and an International cohort enrolled at study sites throughout Europe and Asia. The primary end point was sustained virological response (SVR). RESULTS: The study included 682 patients; 80.2% had genotype 3 infection. In the intent-to-treat population, SVR rates were 66.5%, 64.3%, and 56.6% in groups A, B, and C, and were similar in Asian and white patients. Treatment differences (A vs. B and A vs. C) failed to reach the predefined margin for noninferiority of -10%; and thus groups B and C failed to show noninferiority relative to group A. Among patients with undetectable HCV RNA at week 4, SVR rates were 75.3%, 75.9%, and 72.4%, respectively. Relapse rates were 17.8%, 16.3%, and 29.3%, respectively. Treatment-emergent serious adverse events were highest in group A and lowest in group C, and adverse events leading to discontinuation were similar across treatment arms. CONCLUSIONS: For patients with chronic hepatitis C genotype 2/3 infection, 24weeks of peginterferon alfa-2b (1.5μg/kg/wk) plus weight-based ribavirin remains a standard-of-care therapy; however, treatment for 16weeks may be considered for patients with undetectable HCV RNA at week 4 of the treatment.
Authors: Pankaj Puri; Anil C Anand; Vivek A Saraswat; Subrat K Acharya; Shiv K Sarin; Radha K Dhiman; Rakesh Aggarwal; Shivaram P Singh; Deepak Amarapurkar; Anil Arora; Mohinish Chhabra; Kamal Chetri; Gourdas Choudhuri; Vinod K Dixit; Ajay Duseja; Ajay K Jain; Dharmesh Kapoor; Premashis Kar; Abraham Koshy; Ashish Kumar; Kaushal Madan; Sri P Misra; Mohan V G Prasad; Aabha Nagral; Amarendra S Puri; R Jeyamani; Sanjiv Saigal; Samir Shah; Praveen K Sharma; Ajit Sood; Sandeep Thareja; Manav Wadhawan Journal: J Clin Exp Hepatol Date: 2014-06-24
Authors: Wolf Peter Hofmann; Stefan Mauss; Thomas Lutz; Andreas Schober; Klaus Böker; Gero Moog; Axel Baumgarten; Heike Pfeiffer-Vornkahl; Ulrich Alshuth; Dietrich Hüppe; Heiner Wedemeyer; Michael P Manns; Eckart Schott Journal: PLoS One Date: 2015-07-31 Impact factor: 3.240
Authors: Benjamin Heidrich; Steffen B Wiegand; Peter Buggisch; Holger Hinrichsen; Ralph Link; Bernd Möller; Klaus H W Böker; Gerlinde Teuber; Hartwig Klinker; Elmar Zehnter; Uwe Naumann; Heiner W Busch; Benjamin Maasoumy; Undine Baum; Svenja Hardtke; Michael P Manns; Heiner Wedemeyer; Jörg Petersen; Markus Cornberg Journal: PLoS One Date: 2014-10-10 Impact factor: 3.240