Novel Interferon-Free Regimen for Hepatitis C Produces High Treatment Adherence, Sustained Viral Response

High medication adherence and sustained viral response (SVR) has been reported in hepatitis C (HCV) patients taking an interferon-free, short-duration, oral regimen of ribavirin (RBV) combined with 3 direct-acting antivirals (DAAs) that are currently in phase 2b/3 clinical trials.

In a poster presented at the 2013 annual meeting of the American Association for the Study of Liver Disease, held November 1-5 in Washington, DC, Marc Bourlière, MD, and colleagues from the l’Hôpital Saint Joseph in Marseille, France, used an electronic medication monitoring system to track adherence over duration of treatment, as well as assist in analyzing the effect of changes in adherence on treatment effectiveness.

The data was drawn from the AVIATOR study, a randomized, open-label, multicenter phase 2b trial evaluating three DAAs in various combinations with or without RBV. Those DAAs included ABT-450, an HCV NS3/4A protease inhibitor; ABT-267, an HCV NS5B protease inhibitor; and ABT-333, an HCV RNA polymerase inhibitor. ABT-450 is combined with the CYTP3A4 inhibitor ritonavir at low doses to achieve therapeutic action with once-daily dosing.

Throughout the study, a total of 327 patients — all of whom had chronic HCV genotype 1 without evidence of liver cirrhosis — were treated with the triple DAA combination (3D) plus RBV for 8, 12, or 24 weeks. The study population included both treatment-naïve individuals and previous null responders. Previously reported efficacy results showed that SVR rates above 90% across all subject categories were achieved when 3D + RBV therapy was maintained for 12 or 24 weeks.

Adherence was evaluated by using bottles with a Medication Event Monitoring System. Time and dates of bottle opening were recorded for each bottle over the duration of the study. Medication adherence measures included overall adherence, which was defined as the percentage of prescribed doses; correct dosing, defined as the percentage of days with the correct number of doses taken; and timing adherence, defined as the percentage of doses taken within the prescribed interval.

When adherence data was compared among groups with different durations of treatment, the 8- and 12-week groups were similar across all adherence measures. The treatment-naïve group and prior null responders in the 12- or 24-week treatment arms didn’t differ in their adherence characteristics for any drug.

However, differences were seen along several axes between the 12- and 24-week treatment groups, as the second 12 weeks of the 24-week treatment arm accounted for decreased adherence. Nevertheless, no significant adherence differences between the 12- and 24-week treatment groups were seen in the first 12 weeks of treatment.

Timing adherence for all three DAAs, correct dosing of ABT-333, and overall medication adherence rates were all lower in the second 12 weeks of the 24-week treatment arm. However, SVR rates were comparable between the groups, as 97% of the 12-week groups achieved SVR, compared to 94% of the 24-week groups. Overall, the SVR12 rate for patients with at least 80% overall adherence for all drugs was 95.9%; among the 28 patients with less than 80% adherence to any drug, SVR12 was achieved by 92.9% of them.

The researchers noted that overall high adherence rates for all treatment arms contributed to the high SVR rates seen in the study. Although mean adherence dropped during the second 12 weeks of treatment, it didn’t impact SVR rates. Twenty-four weeks of treatment has previously been shown to produce no additional gains in SVR rate among the treatment-naïve and null responder HCV groups studied.

The poster authors also noted that a combination formulation of ABT-450 + ritonavir + ABT-267 in once-daily dosing, together with twice-daily ABT-333, is currently in phase 3 trials, which significantly reduced pill count from the instant study.

The authors disclosed support from AbbVie for design, study conduct, analysis, medical writing, and funding, as well as AbbVie’s participation in content approval and data interpretation and review.