Shorter treatment could significantly reduce costs of therapy.
Real-time response guided therapycan shorten treatment duration with direct-acting antiviral (DAA) agents in up to half of patients infected with hepatitis C virus (HCV), without compromising efficacy or patient safety.
A standard 12-week treatment regimen could be shortened to as little as six weeks without compromising efficacy in 50 percent of patients. Treatment currently is standardized to be given for a set period of time, usually 12 weeks, rather than being tailored to the individual patient.
A personalized medicine technique called modeling-based response-guided therapy can reduce treatment times when possible. “There's a potential to save up to 20 percent of the costs of hepatitis C drugs,” said co-first author Harel Dahari, PhD, co-director of the Program for Experimental and Theoretical Modeling in the division of hepatology of Loyola Medicine and Loyola University Chicago Stritch School of Medicine.
Data from the study was presented on November 12, 2018, at the American Association for the Study of Liver Diseases annual meeting in San Francisco.
The advent of all-oral DAA treatment has changed the landscape of HCV management. However, the high costs of DAA therapy have become a major barrier to viral elimination. “Recently, we have demonstrated via retrospective analyses that treatment duration with DAA could have been shortened in a substantial proportion of patients by using mathematical modeling-based response guided therapy,” said Dahari.
For the first time, researchers prospectively evaluated the efficacy and safety of reducing duration of treatment using real-time response guided therapy with different DAA regimens in HCV infected patients. The proof-of-concept pilot study enrolled 22 HCV patients, with an average age of 50 years, with compensated liver disease, genotypes 1 to 6, who were either treatment-naÃ¯ve or interferon-experienced.The most common genotype was genotype 1b (59 percent).
Patients were treated with one of 4 DAA regimens (sofosbuvir/velpatasvir, elbasvir/grazoprevir, sofosbuvir/ledipasvir and glecaprevir/pibrentasvir)according to the investigators’ discretion. Viral load was measured at baseline, at day 2 and at weeks 1, 2 and 4 after treatment initiation.
Mathematical modeling predicted that treatment duration could be shortened to 10 weeks in 1 patient (5 percent), 8 weeks in 8 patients (36 percent) and 6 weeks in 2 patients (9 percent). Of the 22 patients, 19 patients have completed therapy. All of them had undetectable viral load at the end of treatment. Virtually all (18 of 19) who have completed therapy remained HCV-undetectable at week 4 post-treatment.
Some 15 patients have reached week 12 post-treatment, and 14 of 15 patients have attained undetectable HCV for 12 or more weeks after the end of treatment(SVR12). The only patient who relapsed thus far was a treatment naÃ¯ve, non-cirrhotic, genotype 3 male, treated with sofosbuvir/velpatasvir for 6 weeks.
Virus sequencing did not identify baseline or treatment emergent resistant-associated variants. No significant side effects were observed among the patients treated with DAA.
Dahari said that in addition to cutting costs, “shorter treatment regimens would make it easier to treat hepatitis C patients who have limited health insurance benefits.”
A multicenter trial is currently underway to validate these results on a larger scale.