John M Vierling1, Mitchell Davis2, Steven Flamm3, Stuart C Gordon4, Eric Lawitz5, Eric M Yoshida6, Joseph Galati7, Velimir Luketic8, Jonathan McCone9, Ira Jacobson10, Patrick Marcellin11, Andrew J Muir12, Fred Poordad5, Lisa D Pedicone13, Janice Albrecht13, Clifford Brass13, Anita Y M Howe13, Lynn Y Colvard13, Frans A Helmond13, Weiping Deng13, Michelle Treitel13, Janice Wahl13, Jean-Pierre Bronowicki14. 1. Baylor College of Medicine, Houston, TX, United States. Electronic address: vierling@bcm.tmc.edu. 2. South Florida Center of Gastroenterology, Wellington, FL, United States. 3. Northwestern Feinberg School of Medicine, Chicago, IL, United States. 4. Henry Ford Hospital, Detroit, MI, United States. 5. The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, United States. 6. University of British Columbia and Vancouver General Hospital, Vancouver, Canada. 7. Liver Specialists of Texas, Houston, TX, United States. 8. Virginia Commonwealth University School of Medicine, Richmond, VA, United States. 9. Mt. Vernon Endoscopy Center, Alexandria, VA, United States. 10. Weill Cornell Medical College, New York, NY, United States. 11. Universite Denis Diderot-Paris, Paris, France. 12. Duke University School of Medicine, Durham, NC, United States. 13. Merck Sharp & Dohme Corp, Whitehouse Station, NJ, United States. 14. INSERM U954, Centre Hospitalier Universitaire de Nancy, Université de Lorraine, Vandoeuvre-lès-Nancy, France.
Abstract
BACKGROUND & AIMS: Boceprevir with peginterferon/ribavirin (BOC/PR) leads to significantly higher sustained virological response (SVR) rates in patients with chronic hepatitis C and partial response or relapse after prior treatment with peginterferon/ribavirin. We studied the efficacy of BOC/PR in patients with prior treatment failure, including those with a null response (<2-log10 decline in HCV RNA), to peginterferon/ribavirin. METHODS: Patients in the control arms of boceprevir Phase 2/3 studies who did not achieve SVR were re-treated with BOC/PR for up to 44 weeks. Patients enrolling >2 weeks after end-of-treatment in the prior study received PR for 4 weeks before adding boceprevir. RESULTS: Of 168 patients enrolled, four discontinued from the PR lead-in and 164 received BOC/PR. Baseline viral load was >800,000 IU/ml in 77% of patients; 62% had HCV genotype 1a, and 10% were cirrhotic. In the ITT analysis (all 168 patients), SVR was achieved in 20 (38%) of 52 patients with prior null response, 57 (67%) of 85 with prior partial response, and 27 (93%) of 29 with prior relapse. In the mITT analysis (164 BOC/PR-treated patients), SVR rates were 41% (20/49), 67% (57/85), and 96% (27/28), respectively. SVR was achieved by 48% of patients with <1-log10 decline in HCV-RNA after lead-in and 76% of those with ⩾ 1-log10 decline or undetectable HCV-RNA after lead-in. The most common adverse events were anemia (49%), fatigue (48%), and dysgeusia (35%); 8% of patients discontinued due to adverse events. CONCLUSIONS: Re-treatment with BOC/PR improved SVR rates in all patient subgroups, including those with prior null response.
BACKGROUND & AIMS:Boceprevir with peginterferon/ribavirin (BOC/PR) leads to significantly higher sustained virological response (SVR) rates in patients with chronic hepatitis C and partial response or relapse after prior treatment with peginterferon/ribavirin. We studied the efficacy of BOC/PR in patients with prior treatment failure, including those with a null response (<2-log10 decline in HCV RNA), to peginterferon/ribavirin. METHODS:Patients in the control arms of boceprevir Phase 2/3 studies who did not achieve SVR were re-treated with BOC/PR for up to 44 weeks. Patients enrolling >2 weeks after end-of-treatment in the prior study received PR for 4 weeks before adding boceprevir. RESULTS: Of 168 patients enrolled, four discontinued from the PR lead-in and 164 received BOC/PR. Baseline viral load was >800,000 IU/ml in 77% of patients; 62% had HCV genotype 1a, and 10% were cirrhotic. In the ITT analysis (all 168 patients), SVR was achieved in 20 (38%) of 52 patients with prior null response, 57 (67%) of 85 with prior partial response, and 27 (93%) of 29 with prior relapse. In the mITT analysis (164 BOC/PR-treated patients), SVR rates were 41% (20/49), 67% (57/85), and 96% (27/28), respectively. SVR was achieved by 48% of patients with <1-log10 decline in HCV-RNA after lead-in and 76% of those with ⩾ 1-log10 decline or undetectable HCV-RNA after lead-in. The most common adverse events were anemia (49%), fatigue (48%), and dysgeusia (35%); 8% of patients discontinued due to adverse events. CONCLUSIONS: Re-treatment with BOC/PR improved SVR rates in all patient subgroups, including those with prior null response.
Authors: Chiara Rosso; Maria Lorena Abate; Alessia Ciancio; Silvia Strona; Gian Paolo Caviglia; Antonella Olivero; Giovanni Antonio Touscoz; Mario Rizzetto; Rinaldo Pellicano; Antonina Smedile Journal: World J Gastroenterol Date: 2014-09-28 Impact factor: 5.742
Authors: Spilios Manolakopoulos; Hariklia Kranidioti; John Goulis; John Vlachogiannakos; John Elefsiniotis; Elias A Kouroumalis; John Koskinas; George Kontos; Eftychia Evangelidou; Polyxeni Doumba; Emmanuel Sinakos; Ιrini Vafiadou; Mairi Koulentaki; George Papatheodoridis; Evangelos Akriviadis Journal: Ann Gastroenterol Date: 2015 Oct-Dec