Jordan J Feld1, Ira M Jacobson2, Donald M Jensen3, Graham R Foster4, Stanislas Pol5, Edward Tam6, Maciej Jablkowski7, Hanna Berak8, John M Vierling9, Eric M Yoshida10, Héctor R Perez-Gomez11, Astrid Scalori12, Gregory J Hooper12, Jorge A Tavel13, Mercidita T Navarro13, Saba Shahdad12, Rohit Kulkarni13, Sophie Le Pogam14, Isabel Nájera15, Simon Eng13, Chin Yin Lim13, Nancy S Shulman13, Ellen S Yetzer13. 1. Toronto Centre for Liver Disease, McLaughlin-Rotman Centre for Global Health, Toronto, ON, Canada. Electronic address: jordan.feld@uhn.ca. 2. Center for the Study of Hepatitis C, Weill Cornell Medical College, New York, NY, USA. 3. Center for Liver Diseases, University of Chicago Hospitals, Chicago, IL, USA. 4. Queen Mary, University of London, Institute of Cellular and Molecular Sciences, London, UK. 5. Hôpital Cochin, Université Paris Descartes and INSERM U1610, Paris, France. 6. LAIR Centre, Vancouver, BC, Canada. 7. Medical University of Lodz, Lodz, Poland. 8. Hospital of Infectious Diseases, Warsaw, Poland. 9. Baylor College of Medicine, Houston, TX, USA. 10. University of British Columbia, Vancouver, BC, Canada. 11. Hospital Civil de Guadalajara, Instituto de Patologia Infecciosa, Universidad de Guadalajara, Guadalajara, Mexico. 12. Roche Products Ltd, Welwyn, UK. 13. Genentech, South San Francisco, CA, USA. 14. Hoffmann-La Roche Inc, Nutley, NJ, USA. 15. F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Abstract
BACKGROUND & AIMS: Chronic hepatitis C treatment for prior non-responders to peginterferon (PegIFN)/ribavirin remains suboptimal. The MATTERHORN study evaluated regimens containing ritonavir-boosted danoprevir (danoprevir/r) in prior PegIFN alfa/ribavirinnon-responders. METHODS:Prior partial responders (N=152) were randomized to 24 weeks of twice-daily danoprevir/r 100/100mg, mericitabine 1000 mg and ribavirin 1000/1200 mg (IFN-free); danoprevir/r plus PegIFN alfa-2a/ribavirin (triple); or danoprevir/r, mericitabine and PegIFN alfa-2a/ribavirin (Quad). Prior null responders (N=229) were randomized to 24 weeks of IFN-free therapy, or quad alone (Quad 24) or quad plus 24-weeks of PegIFN alfa-2a/ribavirin (Quad 48). The primary endpoint was sustained virological response (HCV RNA <25 IU/ml) 24 weeks after end-of-treatment (SVR24). Due to high relapse rates, genotype (G) 1a patients in IFN-free arms were offeredadditional PegIFN alfa-2a/ribavirin. RESULTS: Among prior partial responders, SVR24 rates were 46.2%, 51.0%, and 86.0%, in the IFN-free, Triple and Quad arms, respectively; among prior null responders, SVR24 rates were 45.5%, 80.5%, and 83.8% respectively. Relapse rates were lower and SVR24 rates higher in G1b-infected than G1a-infected patients. SVR24 rates in G1a and G1b patients randomized to Quad were 75.0% and 96.2%, respectively, in the partial Quad arm, and 68.1% and 100%, respectively, in the null Quad 24 arm. Treatment failure was associated with resistance to danoprevir, but not to mericitabine, and was more common in G1a infected patients. Treatment was well-tolerated. CONCLUSIONS:Danoprevir/r, mericitabine plus PegIFN alfa-2a/ribavirin was well-tolerated and produced high overall SVR24 rates in prior partial and null responders to PegIFN alfa/ribavirin. In contrast, IFN-free regimens were associated with unacceptably high relapse rates.
RCT Entities:
BACKGROUND & AIMS:Chronic hepatitis C treatment for prior non-responders to peginterferon (PegIFN)/ribavirin remains suboptimal. The MATTERHORN study evaluated regimens containing ritonavir-boosted danoprevir (danoprevir/r) in prior PegIFN alfa/ribavirin non-responders. METHODS: Prior partial responders (N=152) were randomized to 24 weeks of twice-daily danoprevir/r 100/100mg, mericitabine 1000 mg and ribavirin 1000/1200 mg (IFN-free); danoprevir/r plus PegIFN alfa-2a/ribavirin (triple); or danoprevir/r, mericitabine and PegIFN alfa-2a/ribavirin (Quad). Prior null responders (N=229) were randomized to 24 weeks of IFN-free therapy, or quad alone (Quad 24) or quad plus 24-weeks of PegIFN alfa-2a/ribavirin (Quad 48). The primary endpoint was sustained virological response (HCV RNA <25 IU/ml) 24 weeks after end-of-treatment (SVR24). Due to high relapse rates, genotype (G) 1a patients in IFN-free arms were offered additional PegIFN alfa-2a/ribavirin. RESULTS: Among prior partial responders, SVR24 rates were 46.2%, 51.0%, and 86.0%, in the IFN-free, Triple and Quad arms, respectively; among prior null responders, SVR24 rates were 45.5%, 80.5%, and 83.8% respectively. Relapse rates were lower and SVR24 rates higher in G1b-infected than G1a-infected patients. SVR24 rates in G1a and G1b patients randomized to Quad were 75.0% and 96.2%, respectively, in the partial Quad arm, and 68.1% and 100%, respectively, in the null Quad 24 arm. Treatment failure was associated with resistance to danoprevir, but not to mericitabine, and was more common in G1a infected patients. Treatment was well-tolerated. CONCLUSIONS:Danoprevir/r, mericitabine plus PegIFN alfa-2a/ribavirin was well-tolerated and produced high overall SVR24 rates in prior partial and null responders to PegIFN alfa/ribavirin. In contrast, IFN-free regimens were associated with unacceptably high relapse rates.
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