Treatment-Naive Genotype 1b With Compensated Cirrhosis

Recommended and alternative regimens listed by evidence level and alphabetically for:

Treatment-Naive Genotype 1b Patients With Compensated Cirrhosisa 

RECOMMENDED DURATION RATING
Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) 12 weeks I, A
Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg)b 12 weeks I, A
Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) 12 weeks I, A
Daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) 12 weeks I, A
ALTERNATIVE DURATION RATING
Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) with dasabuvir (600 mg) as part of an extended-release regimen or plus twice-daily dosed dasabuvir (250 mg)c 12 weeks I, A
a For decompensated cirrhosis, please refer to the appropriate section.
b This is a 3-tablet coformulation. Please refer to the prescribing information.
c Please see statement on FDA warning regarding the use of paritaprevir/ritonavir/ombitasvir ± dasabuvir in patients with cirrhosis.

 

For genotype 1b-infected, treatment-naive patients with compensated cirrhosis, there are 4 recommended regimens with comparable efficacy. The alternative regimen is classified as such because, compared to the recommended regimens, it requires a longer duration of treatment, involves greater prescribing complexity, is potentially less efficacious, and/or there are limited supporting data.

Recommended Regimens

Elbasvir/Grazoprevir

The recommendation for use of daily fixed-dose elbasvir (50 mg)/grazoprevir (100 mg) in cirrhotic patients with genotype 1 infection is based on 92 patients (22% of the study cohort) in the phase 3 C-EDGE trial who had Metavir F4 disease (Zeuzem, 2015f). SVR12 was 97% in the subgroup of cirrhotic patients. A similar 97% (28/29) SVR12 rate had previously been demonstrated in genotype 1 cirrhotic treatment-naive patients treated with 12 weeks of elbasvir/grazoprevir without ribavirin in the open-label phase 2 C-WORTHY trial, which enrolled both HCV-monoinfected and HIV/HCV-coinfected patients (Lawitz, 2015c). Presence or absence of cirrhosis does not appear to alter the efficacy of the elbasvir/grazoprevir regimen (Lawitz, 2015c); (Zeuzem, 2017).

Glecaprevir/Pibrentasvir

EXPEDITION-1 investigated use of the daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120 mg) administered as three 100 mg/40 mg fixed-dose combination pills in DAA-naive (75%) or -experienced (interferon or peginterferon ± ribavirin, or sofosbuvir plus ribavirin ± peginterferon) patients with compensated cirrhosis. Of 146 patients with genotype 1, 2, 4, 5, or 6 given 12 weeks of glecaprevir/pibrentasvir, 145 (99%) achieved SVR12; all genotype 1b patients achieved SVR (Forns, 2017).

EXPEDITION-2, a study of glecaprevir/pibrentasvir in 153 HIV/HCV-coinfected adults with genotype 1, 2, 3, 4, 5, or 6, utilized 8 weeks of treatment for noncirrhotic patients and 12 weeks for cirrhotic patients (the recommended durations approved by the FDA). The overall SVR12 rate was 98% and there were no observed virologic failures among the 94 patients with genotype 1 infection (Rockstroh, 2017). In EXPEDITION-1 and EXPEDITION-2, neither subtype (1a vs 1b) nor the presence of baseline RASs impacted SVR12 results in DAA-naive genotype 1 patients.

Ledipasvir/Sofosbuvir

The daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) was approved by the FDA for the treatment of genotype 1 infection in treatment-naive patients based on 2 registration trials: ION-1 (865 treatment-naive patients; those with cirrhosis were included) and ION-3 (647 treatment-naive patients; those with cirrhosis were excluded). ION-1 investigated length of treatment (12 weeks vs 24 weeks) and the need for ribavirin (Afdhal, 2014a). SVR12 rates were 97% to 99% across all study arms with no difference in SVR based on length of treatment, use of ribavirin, or genotype 1 subtype. Sixteen percent of participants enrolled were classified as having cirrhosis. There was no difference in SVR12 rate in those with cirrhosis (97%) versus those without cirrhosis (98%).

Sofosbuvir/Velpatasvir

The daily fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg) for 12 weeks was approved by the FDA for the treatment of genotype 1 infection in treatment-naive patients based on ASTRAL-1. This placebo-controlled trial involved a 12-week course of sofosbuvir/velpatasvir administered to 624 participants with genotype 1, 2, 4, 5, or 6 who were treatment-naive (n=423) or previously treated with interferon-based therapy, with or without ribavirin or a protease inhibitor (n=201); (Feld, 2015). Of the 328 genotype 1 patients included, 323 achieved SVR with no difference in SVR observed by subtype (98% 1a, 99% 1b). Of 121 participants (all genotypes) classified as having cirrhosis, 120 achieved SVR (99%). Baseline NS5A RASs (at 15% cutoff)—reported in 11% of genotype 1a and 18% of genotype 1b participant samples tested—did not influence SVR rate for genotype 1 (Hézode, 2016). Of the 2 virologic failures in ASTRAL-1 (<1% of treated participants), both were genotype 1 and had baseline RASs. There was no significant difference in the rates of adverse events in the sofosbuvir/velpatasvir vs placebo groups.

The phase 3 POLARIS-2 study randomized 941 DAA-naive patients with genotypes 1, 2, 3, 4, 5, or 6—19% with compensated cirrhosis—to receive either 8 weeks of sofosbuvir (400 mg)/velpatasvir (100 mg)/voxilaprevir (100mg) or 12 weeks of sofosbuvir/velpatasvir (Jacobson, 2017). Of participants treated with sofosbuvir/velpatasvir, 170/172 (99%) with genotype 1a and 57/59 (97%) with genotype 1b achieved SVR with a single relapse observed with each subtype.
 

Alternative Regimen

Paritaprevir/Ritonavir/Ombitasvir + Dasabuvir

The daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) plus twice-daily dosed dasabuvir (250 mg) was approved by the FDA for the treatment of genotype 1b infection in treatment-naive patients based on 3 registration trials: SAPPHIRE-I (151 treatment-naive patients with genotype 1b without cirrhosis); PEARL-III (419 treatment-naive patients with genotype 1b without cirrhosis); and TURQUOISE-II (119 treatment-naive and -experienced patients with genotype 1b and cirrhosis). TURQUOISE-II enrolled treatment-naive and -experienced patients with Child-Turcotte-Pugh class A cirrhosis to receive either 12 weeks or 24 weeks of paritaprevir/ritonavir/ombitasvir + dasabuvir and ribavirin. Overall SVR12 rates were 98.5% in the 12-week arm and 100% in the 24-week arm (Poordad, 2014).

To address the need for ribavirin with this regimen in patients with genotype 1b and cirrhosis, the TURQUOISE-III study evaluated the safety and efficacy of paritaprevir/ritonavir/ombitasvir + dasabuvir without ribavirin for 12 weeks in patients with genotype 1b infection and compensated cirrhosis. Sixty patients (62% men; 55% treatment-experienced; 83% with the IL28B non-CC genotype; 22% with platelet counts <90 x 109/L; 17% with albumin <3.5 g/dL) were enrolled. All patients completed treatment and all achieved SVR12. Based on this study, treating patients with genotype 1b with paritaprevir/ritonavir/ombitasvir + dasabuvir without ribavirin is recommended, regardless of prior treatment experience or the presence of compensated cirrhosis (Feld, 2016).

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Last update: 
September 21, 2017
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