Laird Harrison

March 16, 2016

SAN FRANCISCO — For patients with hepatitis C who are receiving opioid substitutes, the once-daily single-tablet combination of sofosbuvir plus ledipasvir (Harvoni Gilead Sciences) is well tolerated and effective, according to an analysis of data from the phase 3 ION studies.

"As long as you anticipate drug interactions, opiate therapy should not prevent treatment," said Nancy Reau, MD, from Rush University Medical Center in Chicago, who presented the finding here at the International Conference on Viral Hepatitis 2016.

A disproportionate number of people who inject drugs are infected with hepatitis C. Treatment protects the livers of infected people and also prevents transmission of the disease, Dr Reau told Medscape Medical News.

In fact, there has been a sharp increase in the number of Americans infected with hepatitis C as a result of injected opioids in recent years, according to data presented at the meeting by Christian Ramers, MD, from the Family Health Centers of San Diego.

Although interferon-based treatments have proven successful in people taking opioid substitutes, few studies have examined treatment with direct-acting antiviral drugs, such as sofosbuvir and ledipasvir, Dr Reau explained.

To fill that gap, she and her colleagues analyzed data from the ION studies.

The open-label ION studies evaluated the fixed-dose combination of the nucleotide analogue polymerase inhibitor sofosbuvir and the NS5A inhibitor ledipasvir in patients with genotype 1 hepatitis C. Participants were randomly assigned to receive the combination, with or without ribavirin, for 8, 12, or 24 weeks. There was a high rate of sustained viral response in all groups.

In their analysis, Dr Reau and her colleagues compared 70 ION patients who were receiving opioid substitutes with 1882 who were not.

Age, sex, race, and rates of cirrhosis were similar in the two groups, but there were more treatment-naïve patients receiving opioid substitutes than not receiving such therapy (89% vs 77%).

The opioid substitute was methadone in 57% of the patients and buprenorphine in 43%.

The combination was effective in both groups.

Table. Outcomes in the Two Groups of Patients From the ION Studies

Outcome Opioid Substitute, % (n = 70) No Opioid Substitute, % (n = 1882) P Value
Treatment completion 97 98 .40
Adherence ≥80% 93 92 .042
Sustained viral response at 12 weeks 94 97 .29
Adverse events 89 80 .07
Serious adverse events 4 3 .43


When the combination therapy included ribavirin, adverse events were more common in those receiving opioid substitutes than in those not receiving such therapy (90% vs 74%). But when the combination did not include ribavirin, there was no difference in adverse events between the two groups (86% vs 86%).

In all groups, common adverse events included fatigue, headache, nausea, insomnia, irritability, and asthenia.

After the presentation, a member of the audience asked Dr Reau why people who were actively injecting drugs were excluded from the ION studies. Dr Reau explained that this was done to minimize the variables.

Another member of the audience asked whether people using cannabis were excluded.

"I do know that drug analysis was done throughout the studies, but no patient was discontinued as a result of a positive toxicology screen," Dr Reau reported. "So you might have had to be pretty pristine to get in, but I imagine as we look at this population going forward, you will find that they were not all pristine for the duration of the study."

The finding that the treatment works well in patients taking opioid substitution therapy is "good news," said session moderator Ji-Dong Jia, MD, PhD, from Capital Medical University in Beijing.

Some health plans restrict coverage of direct-acting antiviral therapies in patients who are using opioid substitutes. "This shows that the efficacy is not compromised," he told Medscape Medical News, and the data could be used to make a case for eliminating these restrictions.

This study was funded by Gilead Sciences. Dr Reau reports relationships with AbbVie, Bristol-Myers Squibb, Gilead Sciences, and Merck. Dr Jia reports relationships with AbbVie, Bristol-Myers Squibb, Gilead Sciences, and Roche Laboratories.

International Conference on Viral Hepatitis (ICVH) 2016: Abstract 22. Presented March 14, 2016.


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