The efficacy and safety of telaprevir - a new protease inhibitor against hepatitis C virus

被引:44
作者
Gentile, Ivan [1 ]
Carleo, Maria Aurora [1 ]
Borgia, Federico [2 ,3 ]
Castaldo, Giuseppe [2 ,3 ]
Borgia, Guglielmo [1 ]
机构
[1] Univ Naples Federico II, Dipartimento Med Pubbl & Sicurezza Sociale, Sez Malattie Infett Ed 18, I-80131 Naples, Italy
[2] Univ Naples Federico II, Dipartimento Biochim & Biotecnol Med, I-80131 Naples, Italy
[3] CEINGE Biotecnol Avanzate SCarl, Naples, Italy
关键词
combination therapy; hepatitis C virus; pegylated-interferon; protease inhibitors; resistance; ribavirin; telaprevir; TREATMENT-NAIVE SUBJECTS; NS3-4A SERINE-PROTEASE; PEGINTERFERON ALPHA-2A; RESISTANCE MUTATIONS; PLUS RIBAVIRIN; INTERFERON THERAPY; NATURAL PREVALENCE; REPLICON CELLS; VIRAL-RNA; IN-VITRO;
D O I
10.1517/13543780903501505
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Importance of the field. Hepatitis C virus (HCV) is the main agent of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma in the western world. It affects more than 170 million people worldwide. HCV treatment, based on the combination of Peg-interferon and ribavirin, is effective in about 50% of treated patients. Therefore, there is a need to develop new drugs active against HCV. Areas covered in this review. Data were obtained by searching for all full articles on Medline and abstracts presented at major international congresses on viral hepatitis. What the reader will gain: A review of clinical data about the efficacy and safety of telaprevir (VX-950), the HCV protease inhibitor that is in the most advanced phase of clinical development. Take home message: Telaprevir has an acceptable pharmacokinetic profile and seems to be a potent antiviral drug against HCV, although, owing to a low genetic barrier, resistant variants emerge within a few days when used in monotherapy, thereby decreasing its efficacy. Consequently, telaprevir has been combined with pegylated-interferon and ribavirin in clinical trials. This triple combination is more effective but has a higher rate of adverse events (notably rash) than the standard of care, despite the shorter duration of therapy.
引用
收藏
页码:151 / 159
页数:9
相关论文
共 54 条
[1]   Epidemiology of hepatitis C virus infection [J].
Alter, Miriam J. .
WORLD JOURNAL OF GASTROENTEROLOGY, 2007, 13 (17) :2436-2441
[2]   Long-term outcome after interferon therapy in elderly patients with chronic hepatitis C [J].
Arase, Yasuji ;
Ikeda, Kenji ;
Suzuki, Fumitaka ;
Suzuki, Yoshiyuki ;
Saitoh, Satoshi ;
Kobayashi, Masahiro ;
Akuta, Norio ;
Someya, Takashi ;
Koyama, Rikako ;
Hosaka, Tetsuya ;
Sezaki, Hitomi ;
Kobayashi, Mariko ;
Kumada, Hiromitsu .
INTERVIROLOGY, 2007, 50 (01) :16-23
[3]  
Bacon BR, 2007, AM J MANAG CARE, V13, pS319
[4]   Natural prevalence of HCV variants with decreased susceptibility to NS3-4A protease inhibitors in treatment-naive subjects [J].
Bartels, D. J. ;
Zhou, Y. ;
Zhang, E. ;
Marcial, M. ;
Byrn, R. A. ;
Adiwijaya, B. ;
Lin, C. ;
Kwong, A. D. ;
Kieffer, T. L. .
JOURNAL OF HEPATOLOGY, 2008, 48 :S316-S316
[5]   Natural prevalence of hepatitis C virus variants with decreased sensitivity to NS3•4A protease inhibitors in treatment-naive subjects [J].
Bartels, Doug J. ;
Zhou, Yi ;
Zhang, Eileen Z. ;
Marcial, Michelle ;
Byrn, Randal A. ;
Pfeiffer, Thomas ;
Tigges, Ann M. ;
Adiwijaya, Bambang S. ;
Lin, Chao ;
Kwong, Ann D. ;
Kieffer, Tara L. .
JOURNAL OF INFECTIOUS DISEASES, 2008, 198 (06) :800-807
[6]   RESULTS OF A PROOF OF CONCEPT STUDY (C210) OF TELAPREVIR MONOTHERAPY AND IN COMBINATION WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN IN TREATMENT-NAIVE GENOTYPE 4 HCV PATIENTS [J].
Benhamou, Y. ;
Moussalli, J. ;
Ratziu, V. ;
Lebray, P. ;
Gysen, V. ;
de Backer, K. ;
Ghys, A. ;
van Heeswijk, R. ;
Vangeneugden, I. ;
Picchio, G. ;
Beumont-Mauviel, M. .
JOURNAL OF HEPATOLOGY, 2009, 50 :S6-S6
[7]   Myasthenia gravis during low-dose IFN-α therapy for chronic hepatitis C [J].
Borgia, G ;
Reynaud, L ;
Gentile, I ;
Cerini, R ;
Ciampi, R ;
Dello Russo, M ;
Piazza, M .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 2001, 21 (07) :469-470
[8]   Sustained virological response to interferon-α is associated with improved outcome in HCV-related cirrhosis:: A retrospective study [J].
Bruno, Savino ;
Stroffolini, Tommaso ;
Colombo, Massimo ;
Bollani, Simona ;
Benvegnu, Luisa ;
Mazzella, Giuseppe ;
Ascione, Antonio ;
Santantonio, Teresa ;
Piccinino, Felice ;
Andreone, Pietro ;
Mangia, Alessandra ;
Gaeta, Giovanni B. ;
Persico, Marcello ;
Fagiuoli, Stefano ;
Almasio, Piero L. .
HEPATOLOGY, 2007, 45 (03) :579-587
[9]  
Chen Stephen L, 2006, Int J Med Sci, V3, P47
[10]   A systematic review of the associations between dose regimens and medication compliance [J].
Claxton, AJ ;
Cramer, J ;
Pierce, C .
CLINICAL THERAPEUTICS, 2001, 23 (08) :1296-1310