Ghent University Academic Bibliography

Advanced

Response-guided telaprevir combination treatment for hepatitis C virus infection

Kenneth E Sherman, Steven L Flamm, Nezam H Afdhal, David R Nelson, Mark S Sulkowski, Gregory T Everson, Michael W Fried, Michael Adler, Hendrik W Reesink and Marie Martin, et al. (2011) NEW ENGLAND JOURNAL OF MEDICINE. 365(11). p.1014-1024
abstract
Background : Patients with chronic infection with hepatitis C virus (HCV) genotype 1 often need 48 weeks of peginterferon-ribavirin treatment for a sustained virologic response. We designed a noninferiority trial (noninferiority margin, -10.5%) to compare rates of sustained virologic response among patients receiving two treatment durations. Methods : We enrolled patients with chronic infection with HCV genotype 1 who had not previously received treatment. All patients received telaprevir at a dose of 750 mg every 8 hours, peginterferon alfa-2a at a dose of 180 mu g per week, and ribavirin at a dose of 1000 to 1200 mg per day, for 12 weeks (T12PR12), followed by peginterferon-ribavirin. Patients who had an extended rapid virologic response (undetectable HCV RNA levels at weeks 4 and 12) were randomly assigned after week 20 to receive the dual therapy for 4 more weeks (T12PR24) or 28 more weeks (T12PR48). Patients without an extended rapid virologic response were assigned to T12PR48. Results : Of the 540 patients, a total of 352 (65%) had an extended rapid virologic response. The overall rate of sustained virologic response was 72%. Among the 322 patients with an extended rapid virologic response who were randomly assigned to a study group, 149 (92%) in the T12PR24 group and 140 (88%) in the T12PR48 group had a sustained virologic response (absolute difference, 4 percentage points; 95% confidence interval, -2 to 11), establishing noninferiority. Adverse events included rash (in 37% of patients, severe in 5%) and anemia (in 39%, severe in 6%). Discontinuation of all the study drugs was based on adverse events in 18% of patients overall, as well as in 1% of patients (all of whom were randomly assigned) in the T12PR24 group and 12% of the patients randomly assigned to the T12PR48 group (P<0.001). Conclusions : In this study, among patients with chronic HCV infection who had not received treatment previously, a regimen of peginterferon-ribavirin for 24 weeks, with telaprevir for the first 12 weeks, was noninferior to the same regimen for 48 weeks in patients with undetectable HCV RNA at weeks 4 and 12, with an extended rapid virologic response achieved in nearly two thirds of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ILLUMINATE ClinicalTrials.gov number, NCT00758043.)
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
GENOTYPE-1, PLUS RIBAVIRIN, PEGINTERFERON ALPHA-2A
journal title
NEW ENGLAND JOURNAL OF MEDICINE
N. Engl. J. Med.
volume
365
issue
11
pages
1014 - 1024
Web of Science type
Article
Web of Science id
000294857300009
JCR category
MEDICINE, GENERAL & INTERNAL
JCR impact factor
53.298 (2011)
JCR rank
1/153 (2011)
JCR quartile
1 (2011)
ISSN
0028-4793
DOI
10.1056/NEJMoa1014463
language
English
UGent publication?
no
classification
A1
additional info
ILLUMINATE Study Team: see Supplementary Appendix, URL http://www.nejm.org/doi/suppl/10.1056/NEJMoa1014463/suppl_file/nejmoa1014463_appendix.pdf
copyright statement
I have transferred the copyright for this publication to the publisher
id
1906685
handle
http://hdl.handle.net/1854/LU-1906685
date created
2011-09-22 13:22:13
date last changed
2012-08-07 10:54:31
@article{1906685,
  abstract     = {Background : Patients with chronic infection with hepatitis C virus (HCV) genotype 1 often need 48 weeks of peginterferon-ribavirin treatment for a sustained virologic response. We designed a noninferiority trial (noninferiority margin, -10.5\%) to compare rates of sustained virologic response among patients receiving two treatment durations. 
Methods : We enrolled patients with chronic infection with HCV genotype 1 who had not previously received treatment. All patients received telaprevir at a dose of 750 mg every 8 hours, peginterferon alfa-2a at a dose of 180 mu g per week, and ribavirin at a dose of 1000 to 1200 mg per day, for 12 weeks (T12PR12), followed by peginterferon-ribavirin. Patients who had an extended rapid virologic response (undetectable HCV RNA levels at weeks 4 and 12) were randomly assigned after week 20 to receive the dual therapy for 4 more weeks (T12PR24) or 28 more weeks (T12PR48). Patients without an extended rapid virologic response were assigned to T12PR48. 
Results : Of the 540 patients, a total of 352 (65\%) had an extended rapid virologic response. The overall rate of sustained virologic response was 72\%. Among the 322 patients with an extended rapid virologic response who were randomly assigned to a study group, 149 (92\%) in the T12PR24 group and 140 (88\%) in the T12PR48 group had a sustained virologic response (absolute difference, 4 percentage points; 95\% confidence interval, -2 to 11), establishing noninferiority. Adverse events included rash (in 37\% of patients, severe in 5\%) and anemia (in 39\%, severe in 6\%). Discontinuation of all the study drugs was based on adverse events in 18\% of patients overall, as well as in 1\% of patients (all of whom were randomly assigned) in the T12PR24 group and 12\% of the patients randomly assigned to the T12PR48 group (P{\textlangle}0.001). 
Conclusions : In this study, among patients with chronic HCV infection who had not received treatment previously, a regimen of peginterferon-ribavirin for 24 weeks, with telaprevir for the first 12 weeks, was noninferior to the same regimen for 48 weeks in patients with undetectable HCV RNA at weeks 4 and 12, with an extended rapid virologic response achieved in nearly two thirds of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ILLUMINATE ClinicalTrials.gov number, NCT00758043.)},
  author       = {Sherman, Kenneth E and Flamm, Steven L and Afdhal, Nezam H and Nelson, David R and Sulkowski, Mark S and Everson, Gregory T and Fried, Michael W and Adler, Michael and Reesink, Hendrik W and Martin, Marie and Sankoh, Abdul J and Adda, Nathalie and Kauffman, Robert S and George, Shelley and Wright, Christopher I and Poordad, Fred and ILLUMINATE Study Team, the and Van Vlierberghe, Hans},
  issn         = {0028-4793},
  journal      = {NEW ENGLAND JOURNAL OF MEDICINE},
  keyword      = {GENOTYPE-1,PLUS RIBAVIRIN,PEGINTERFERON ALPHA-2A},
  language     = {eng},
  number       = {11},
  pages        = {1014--1024},
  title        = {Response-guided telaprevir combination treatment for hepatitis C virus infection},
  url          = {http://dx.doi.org/10.1056/NEJMoa1014463},
  volume       = {365},
  year         = {2011},
}

Chicago
Sherman, Kenneth E, Steven L Flamm, Nezam H Afdhal, David R Nelson, Mark S Sulkowski, Gregory T Everson, Michael W Fried, et al. 2011. “Response-guided Telaprevir Combination Treatment for Hepatitis C Virus Infection.” New England Journal of Medicine 365 (11): 1014–1024.
APA
Sherman, K. E., Flamm, S. L., Afdhal, N. H., Nelson, D. R., Sulkowski, M. S., Everson, G. T., Fried, M. W., et al. (2011). Response-guided telaprevir combination treatment for hepatitis C virus infection. NEW ENGLAND JOURNAL OF MEDICINE, 365(11), 1014–1024.
Vancouver
1.
Sherman KE, Flamm SL, Afdhal NH, Nelson DR, Sulkowski MS, Everson GT, et al. Response-guided telaprevir combination treatment for hepatitis C virus infection. NEW ENGLAND JOURNAL OF MEDICINE. 2011;365(11):1014–24.
MLA
Sherman, Kenneth E, Steven L Flamm, Nezam H Afdhal, et al. “Response-guided Telaprevir Combination Treatment for Hepatitis C Virus Infection.” NEW ENGLAND JOURNAL OF MEDICINE 365.11 (2011): 1014–1024. Print.