ABT-450/r-Ombitasvir and Dasabuvir with or without Ribavirin for HCV

被引：579

作者：

Ferenci, Peter ^{[1
]}

Bernstein, David ^{[2
]}

Lalezari, Jacob ^{[3
]}

Cohen, Daniel ^{[9
]}

Luo, Yan ^{[9
]}

Cooper, Curtis ^{[10
]}

Tam, Edward ^{[11
]}

Marinho, Rui T. ^{[12
]}

Tsai, Naoky ^{[13
]}

Nyberg, Anders ^{[4
]}

Box, Terry D. ^{[14
]}

Younes, Ziad ^{[15
]}

Enayati, Pedram ^{[5
]}

Green, Sinikka ^{[6
]}

Baruch, Yaacov ^{[16
]}

Bhandari, Bal Raj ^{[17
]}

Caruntu, Florin Alexandru ^{[18
]}

Sepe, Thomas ^{[19
]}

Chulanov, Vladimir ^{[20
]}

Janczewska, Ewa ^{[21
]}

Rizzardini, Giuliano ^{[22
]}

Gervain, Judit ^{[23
]}

Planas, Ramon ^{[24
]}

Moreno, Christophe ^{[25
]}

Hassanein, Tarek ^{[7
,8
]}

Xie, Wangang ^{[9
]}

King, Martin ^{[9
]}

Podsadecki, Thomas ^{[9
]}

Reddy, K. Rajender ^{[26
]}

机构：

[1] Med Univ Vienna, A-1090 Vienna, Austria

[2] Hofstra North Shore LIJ Sch Med, Manhasset, NY USA

[3] Quest Clin Res, San Francisco, CA USA

[4] Kaiser Permanente, San Diego, CA USA

[5] Calif Liver Inst, Los Angeles, CA USA

[6] eStudySite, La Mesa, CA USA

[7] So Calif Liver Ctr, Coronado, CA USA

[8] So Calif Res Ctr, Coronado, CA USA

[9] AbbVie, N Chicago, IL USA

[10] Univ Ottawa, Ottawa, ON, Canada

[11] Liver & Intestinal Res Ctr, Vancouver, BC, Canada

[12] Ctr Hosp Lisboa Norte, Med Sch Lisbon, Lisbon, Portugal

[13] Queens Med Ctr, Ctr Liver, Honolulu, HI USA

[14] Clin Res Ctr Amer, Murray, UT USA

[15] Gastro One, Germantown, TN USA

[16] Rambam Hlth Care Campus, Haifa, Israel

[17] Delta Res Partners, Bastrop, LA USA

[18] Matei Bals Natl Inst Infect Dis, Bucharest, Romania

[19] Univ Gastroenterol, Providence, RI USA

[20] Cent Res Inst Epidemiol, Moscow, Russia

[21] ID Clin, Myslowice, Poland

[22] Osped L Sacco, Milan, Italy

[23] Szent Gyorgy Hosp, Szekesfehervar, Hungary

[24] Hosp Badalona Germans Trias & Pujol, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Badalona, Spain

[25] Univ Libre Bruxelles, Clin Univ Bruxelles Hop Erasme, Brussels, Belgium

[26] Univ Penn, Philadelphia, PA 19104 USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2014年 / 370卷 / 21期

关键词：

1; HEPATITIS-C; ANTIVIRAL AGENTS; TREATMENT-NAIVE; TELAPREVIR; SOFOSBUVIR; PEGINTERFERON; DACLATASVIR; COMBINATION; INTERFERON; BOCEPREVIR;

D O I：

10.1056/NEJMoa1402338

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND The interferon-free regimen of ABT-450 with ritonavir (ABT-450/r), ombitasvir, and dasabuvir with or without ribavirin has shown efficacy in inducing a sustained virologic response in a phase 2 study involving patients with hepatitis C virus (HCV) genotype 1 infection. We conducted two phase 3 trials to examine the efficacy and safety of this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis. METHODS We randomly assigned 419 patients with HCV genotype 1b infection (PEARL-III study) and 305 patients with genotype 1a infection (PEARL-IV study) to 12 weeks of ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), dasabuvir (250 mg twice daily), and ribavirin administered according to body weight or to matching placebo for ribavirin. The primary efficacy end point was a sustained virologic response (an HCV RNA level of <25 IU per milliliter) 12 weeks after the end of treatment. RESULTS The study regimen resulted in high rates of sustained virologic response among patients with HCV genotype 1b infection (99.5% with ribavirin and 99.0% without ribavirin) and among those with genotype 1a infection (97.0% and 90.2%, respectively). Of patients with genotype 1b infection, 1 had virologic failure, and 2 did not have data available at post-treatment week 12. Among patients with genotype 1a infection, the rate of virologic failure was higher in the ribavirin-free group than in the ribavirin group (7.8% vs. 2.0%). In both studies, decreases in the hemoglobin level were significantly more common in patients receiving ribavirin. Two patients (0.3%) discontinued the study drugs owing to adverse events. The most common adverse events were fatigue, headache, and nausea. CONCLUSIONS Twelve weeks of treatment with ABT-450/r-ombitasvir and dasabuvir without ribavirin was associated with high rates of sustained virologic response among previously untreated patients with HCV genotype 1 infection. Rates of virologic failure were higher without ribavirin than with ribavirin among patients with genotype 1a infection but not among those with genotype 1b infection.

引用

页码：1983 / 1992

页数：10

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