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Response-guided telaprevir combination treatment for hepatitis C virus infection

Sherman, Kenneth E, Flamm, Steven L, Afdhal, Nezam H, Nelson, David R, Sulkowski, Mark S, Everson, Gregory T, Fried, Michael W, Adler, Michael, Reesink, Hendrik W, Martin, Marie, 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
2016-12-19 15:40:03
@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.