Funded by Vertex Pharmaceuticals Inc. and by Tibotec, a division of Janssen-Cilag Ltd. The study sponsors were involved in the trial design and conduct, data collection, and data analysis. Several authors are employees of Vertex Pharmaceuticals Inc.
Article first published online: 24 AUG 2011
Copyright © 2011 American Association for the Study of Liver Diseases
Volume 54, Issue 5, pages 1538–1546, November 2011
How to Cite
Muir, A. J., Poordad, F. F., McHutchison, J. G., Shiffman, M. L., Berg, T., Ferenci, P., Heathcote, E. J., Pawlotsky, J.-M., Zeuzem, S., Reesink, H. W., Dusheiko, G., Martin, E. C., George, S., Kauffman, R. S. and Adda, N. (2011), Retreatment with telaprevir combination therapy in hepatitis C patients with well-characterized prior treatment response. Hepatology, 54: 1538–1546. doi: 10.1002/hep.24549
Potential conflicts of interest: Dr. Muir currently serves as a consultant/advisor to Vertex, Bristol Myers-Squibb, Merck, Pharmasset, Santaris, and Zymogenetics. He received grant funding from Vertex, Anadys, Gilead, GlaxoSmithKline, Idera, Medtronic, Merck, Pfizer, Pharmasset, Santaris, Three Rivers, and Zymogenetics. Dr. Poordad is a consultant/advisor to Abbott, Achillion, Genentech, Gilead, Idenix, Merck/Schering-Plough, Tibotec, Valeant, and Vertex Pharmaceuticals, and is on the speaker's bureau of Genentech, and Gilead. Dr. Shiffman has received consulting and lecture fees from Abbott, Anadys, Biolex, Bristol Myers-Squibb, Celera Diagnostics, Conatus, Gilead Sciences, Human Genome Sciences, Merck/Schering-Plough, Novartis, Pfizer, Roche/Genentech, Romark, Valeant, Vertex Pharmaceuticals and Zymogenetics; and Grant/Research Support from Biolex, Conatus, Gilead Sciences, GlaxoSmithKline, GlobeImmune, Human Genome Sciences, Idenix, Merck/Schering-Plough, Roche/Genentech, Romark, Tibotec, Valeant, Vertex Pharmaceuticals, Wyeth, and Zymogenetics. Dr. Berg has received consulting and lecture fees from Abbott, Bayer, Gilead Sciences, Merck/Schering-Plough, Novartis, Roche/Genentech, Tibotec and Vertex Pharmaceuticals. Dr. Ferenci has received consulting fees from Boehringer Ingelheim, RottaPharm-Madaus, Roche/Genentech, Tibotec and Vertex Pharmaceuticals; and Grant/Research Support from Roche/Genentech. Dr. Heathcote has received consulting and lecture fees from Axcan Pharma, Gilead Sciences, Hoffman-La-Roche, Merck/Schering-Plough and Tibotec, and Grant/Research Support Axcan Pharma, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Hoffman-La-Roche, Intercept Pharma, Merck/Schering-Plough, Tibotec and Vertex Pharmaceuticals.
Dr. Pawlotsky has received consulting fees from Abbott, Anadys, Biotica, Boehringer-Ingelheim, Bristol-Myers Squibb, DebioPharm, Gilead Sciences, GlaxoSmithKline, Idenix, Janssen-Cilag, Madaus-Rottapharm, Merck/Schering-Plough, Novartis, Pfizer, Roche/Genentech, Tibotec Pharmaceuticals, Valeant Pharmaceuticals, and Vertex Pharmaceuticals; and Grant/Research Support from Gilead Sciences and Roche/Genentech. Dr. Zeuzem has received consulting and lecture fees from Abbott, Achillion, Anadys, Bayer, Bristol-Myers Squibb, Gilead Sciences, Human Genome Sciences, Merck/Schering-Plough, Novartis, Pharmasset, Roche/Genentech, Santaris, Tibotec and Vertex Pharmaceuticals. Dr. Reesink served as an advisor for Anadys, Arrows, Chiron, Gilead Sciences, PRA-International, Merck/Schering-Plough, Novartis, Roche Molecular Diagnostics, Roche/Genentech, Tibotec and Astex, and received Grant/Research support from Merck/Schering-Plough, PRA International, Roche/Genentech and has served as a consultant for Vertex Pharmaceuticals. Dr. Dusheiko has received consulting fees from Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Human Genome Sciences, Merck/Schering-Plough, Novartis, Pharmasset, Pfizer, Roche/Genentech, Tibotec, Vertex Pharmaceuticals, and Zymogenetics, travel support from Gilead Sciences, and grant support from, Gilead Sciences, Merck/Schering-Plough, Novartis, Pharmasset, Roche/Genentech, Tibotec and Vertex Pharmaceuticals. Drs Adda, Martin, George and Kauffman are current employees and stock holders of Vertex Pharmaceuticals. Dr. McHutchison is a current employee of Gilead Sciences; has participated in Advisory Committees or review panels for Abbott, Anadys, Biolex, Gilead Sciences, National Genetics Institute, Pharmasset, Pfizer, United Therapeutics; and received Grant/Research Support from GlaxoSmithKline, Globe Immune, Human Genome Sciences, Idera, Intarcia, Medtronics, Merck/Schering Plough, Novartis, Roche/Genentech, Vertex, and Osiris Therapeutics.
- Issue published online: 28 OCT 2011
- Article first published online: 24 AUG 2011
- Accepted manuscript online: 11 JUL 2011 12:30PM EST
- Manuscript Accepted: 27 JUN 2011
- Manuscript Received: 17 MAR 2011
Retreatment with peginterferon alpha and ribavirin (PR) offers a limited chance of sustained virologic response (SVR) in patients who did not achieve SVR with prior PR treatment. This study evaluated the safety and efficacy of telaprevir-based treatment in combination with PR in well-characterized patients who did not achieve SVR in the control arms of three Phase II clinical trials. Patients eligible to enroll in this open-label nonrandomized study either met on-treatment criteria for nonresponse or relapsed after 48 weeks of treatment in the control arm of the three Phase II PROVE studies. The initial protocol was a 24-week regimen: 12 weeks of telaprevir and PR followed by an additional 12 weeks of PR. During the study the protocol was amended to extend PR to 48 weeks for patients with previous null response. All other patients with undetectable hepatitis C virus (HCV) RNA at weeks 4 and 12 received 24 weeks of therapy. Those with detectable HCV RNA at weeks 4 or 12 received a total of 48 weeks of therapy. The overall SVR rate was 59% (69/117). SVR rates with T12PR were 37% (19/51) in prior null responders, 55% (16/29) in prior partial responders, 75% (6/8) in prior breakthroughs, and 97% (28/29) in prior relapsers. The overall relapse rate was 16% (13/83). Adverse events were similar to those in previous trials with telaprevir, with 9% of patients discontinuing due to an adverse event (most commonly rash and anemia). Conclusion: This study demonstrated the benefit of retreatment with a telaprevir-based regimen for patients with well-characterized nonresponse (null and partial) or relapse to a prior course of PR treatment. (HEPATOLOGY 2011;)