Combination treatment of ritonavir-enhanced ABT-450 with ombitasvir, dasabuvir, and ribavirin was shown to be effective in both previously treated and untreated patients with hepatitis C and compensated cirrhosis, according to a recent study [N Engl J Med. DOI:10.1056/NEJMoa1402869]. Efficacy rates were similar between 12- and 24-week treatment groups.
Interferon-free combination regimens containing direct-acting antiviral agents are recommended for patients with hepatitis C and cirrhosis, as regimens containing interferon are particularly toxic for these patients. TURQUOISE-II was a phase 3, randomized, open-label, international trial conducted by Fred Poordad, MD, Texas Liver Institute–University of Texas Health Science Center, and colleagues. The purpose of the trial was to examine the safety and efficacy of a combination of coformulated ABT-450/r-ombitasvir and dasabuvir with ribavirin for 12 or 24 weeks in previously untreated and treated adults with chronic hepatitis C genotype 1 infection and compensated cirrhosis.
The primary efficacy end point was a sustained virologic response (SVR) 12 weeks after the end of treatment. Secondary end points included the percentage of patients with SVR in the 24-week group compared with the 12-week group and the percentage of patients in each group with virologic failure during treatment or relapse after treatment.
During and after treatment, vital signs were monitored, adverse events were assessed, and clinical laboratory testing was performed. The researchers compared the 12- and 24-week groups with the use of a logistic regression model. A total of 380 patients completed the study.
Results showed 191 of 208 patients (91.8%) in the 12-week treatment group had a SVR at post-treatment week 12 compared with 165 of 172 patients (95.9%) in the 24-week treatment group. Virologic failure occurred in 13 of 208 patients (6.2%) in the 12-week group and 4 of 172 patients (2.3%) in the 24-week group. The study did not include patients who had virologic failure with other direct-acting antiviral therapy, which is a potential study limitation. The researchers found that significantly more patients in the 12-week group than the 24-week group had a relapse: 12 of 203 patients (5.9%) compared with 1 of 164 patients (0.6%), respectively.
Adverse events were common in both treatment groups, although rates were slightly higher in the 24-week group compared with the 12-week group. The most frequent grade 3 or 4 laboratory abnormalities that occurred during treatment were elevations in total bilirubin levels (37 of 380 patients; 9.7%), but no patient discontinued treatment because of hyperbilirubinemia. The researchers found grade 1 reductions in hemoglobin were also common. Hemoglobin values of grade ≥2 occurred in 15 patients (7.2%) in the 12-week group and 19 patients (11%) in the 24-week group. A total of 34 patients, all of whom had a SVR at post-treatment week 12, required a dose reduction of ribavirin because of anemia-related adverse events.
In an interview with First Report Managed Care, Dr. Poordad concluded, “This study is a reflection of the evolution of hepatitis therapy. It has demonstrated that we can treat and cure even the most difficult patients, such as those with cirrhosis. Our hope is to eradicate hepatitis C over the next 20 years in the United States.”