Zepatier safe, effective treatment for hepatitis C patients with opioid addictions

August 9, 2016

Patients with hepatitis C who were also being treated for opioid addiction achieved high rates of sustained virologic response with Zepatier, according to data published in the Annals of Internal Medicine.

Gregory J. Dore, MD, head of the Viral Hepatitis Clinical Research Program at the Kirby Institute at UNSW Australia, and colleagues stated that their findings indicated that drug use can be removed as a restriction for receiving interferon-free treatment for hepatitis C virus.

The researchers wrote that the majority of clinical trials of direct-acting antiviral (DAA) therapies have excluded patients with drug use, despite high rates of usage.

“Globally, an estimated 130 million to 170 million persons have hepatitis C virus (HCV) infection,” they wrote. “Morbidity and mortality from chronic HCV infection continue to increase, particularly among persons who inject drugs. In most high-income countries, [people who inject drugs] are the major population affected by HCV, although injection drug use–related HCV epidemics are emerging in many other locales, with an estimated HCV prevalence of 60% to 80%.”

Dore and colleagues conducted a randomized, placebo-controlled, double-blind study of the CO-STAR (Hepatitis C Patients on Opioid Substitution Therapy Antiviral Response) trial. They assessed 301 patients with chronic hepatitis C virus genotype 1, 4, or 6 infections. All patients were treatment-naive, were receiving opioid-agonist therapy with buprenorphine, methadone or buprenorphine-naloxone for at least 3 months before the study and were a minimum of 80% adherent to opioid-agonist therapy visits.

Patients were randomly assigned into two groups: the immediate treatment group, which received Zepatier (elbasvir-grazoprevir, Merck) for 12 weeks and the deferred treatment group, which received a placebo for 12 weeks, no treatment for 4 weeks and elbasvir-grazoprevir for 12 weeks. The researchers measured sustained virologic response at 12 weeks and 24 weeks, as well as viral recurrence and adverse events.

Results showed sustained virologic responses at 12 weeks of 91.5% (95% CI, 86.8-95) for the immediate treatment group and 89.5% (95% CI, 81.5-94.8) for the deferred treatment group. Dore and colleagues reported that drug use at any point did not affect adherence to HCV therapy or sustained virologic response at 12 weeks.

Eighteen patients had posttreatment viral recurrence by the 24-week follow-up, and six of these patients had probable reinfection. The researchers noted that four of these reinfections were in patients who tested positive for opioid use during follow-up, indicating that drug injection was the likely source.

One patient in each treatment group ended treatment due to an adverse event.

“The high level of treatment adherence was extremely encouraging, with no impact of ongoing illicit drug use on either adherence or treatment outcome,” Dore told Healio Internal Medicine. “The study clearly demonstrates that patients with chronic hepatitis C who are on opiate agonist therapy, including those with ongoing illicit drug use, have treatment outcomes equivalent to other patient populations.”

Dore noted that this study did not enroll patients who were injecting drugs not on opiate agonist therapy. Ongoing studies are evaluating direct-acting antiviral therapy in this population.

“Despite the need for further evidence, there are no reasons to deny potential DAA therapy for patients who are injecting,” he continued. “Treatment suitability should be assessed on an individual basis for all patients with chronic hepatitis C. Many patients with chronic hepatitis C who have ongoing illicit drug use are highly motivated to achieve a cure, are able to adhere to DAA therapy and have favorable treatment outcomes. Patients with chronic hepatitis C who have ongoing injecting drug use require assessment for risk of reinfection, but when there is access to harm reduction strategies the risk is relatively low.” – by Chelsea Frajerman Pardes and Will Offit

Disclosures: Dore reports grants from AbbVie, Merck, Bristol-Myers Squibb (BMS), Janssen, and Roche; personal fees frTabom Gilead, AbbVie, Merck, BMS, Janssen, Roche, GlaxoSmithKline, and Abbott Diagnostics; and nonfinancial support from Gilead, AbbVie, Merck, BMS, and Roche, outside the submitted work. Please see the full study for a complete list of all other authors’ relevant financial disclosures.