The trial’s nine arms varied with respect to the specific combination of agents, treatment duration, and patient treatment history.
The patients had a mean age of about 50 years, and approximately 80% were white. Roughly two-thirds had viral subgenotype 1a.
Across trial arms, patients had high rates of SVR12 (85%-99%) and SVR24 (83%-96%), Dr. Kowdley reported.
The optimal regimen appeared to be the combination of three direct-acting antivirals plus ribavirin given for 12 or 24 weeks; the longer treatment duration provided little to no gain.
Among the 247 patients treated with that optimal regimen, relapse and breakthrough were uncommon, each seen in no more than 3% of patients.
Whether treatment naive or null responders, these patients had no clinically meaningful differences in the achievement of SVR by pretreatment predictors.
"In fact, by multivariable analysis, sex, age, race, baseline viral load, subtype, BMI [body mass index], or presence or absence of the need for ribavirin, dose reduction did not influence SVR independently," Dr. Kowdley noted.
Among the patients given the optimal regimen, the rate of discontinuation resulting from adverse events was 2.4%, and the rate of serious adverse events was 1.6%.
"The majority of the adverse events were mild and of the type we often see in clinical trials – headache, fatigue, nausea, insomnia, and diarrhea, and not different between the treatment-naive patients and null responders," Dr. Kowdley commented.
The most common adverse events overall were headache (31%), fatigue (30%), nausea (23%), insomnia (20%), and diarrhea (15%).
The rate of grade 3 laboratory abnormalities was low; the most common, seen in six patients, was total bilirubin level at least three times the upper limit of normal. A single patient had an elevated alanine aminotransferase (ALT) level.
"All of these [cases of hyperbilirubinemia] resolved, typically within 1 week and spontaneously with continued therapy, consistent with the inhibition of OAPT1B1 as a bilirubin transporter that was often observed. None of the bilirubin elevations was associated with an increased ALT level," he noted.
Dr. Kowdley disclosed that he receives grant/research support from AbbVie, Beckman, Boehringer Ingelheim, Bristol Myers Squibb, Gilead/Pharmasset, Ikaria, Intercept, Merck, Mochida, and Vertex, and that he is a consultant to Novartis and an adviser to AbbVie, Gilead, Merck, and Vertex. The trial was sponsored by AbbVie (previously sponsored by Abbott). Dr. Younossi disclosed that he is an advisory committee/board member for Coneatus, Enterome, Gilead, Janssen, Salix, and Vertex.