By Will Boggs MD
April 13, 2015
NEW YORK (Reuters Health) - An all-oral, interferon-free regimen consisting of ombitasvir, paritaprevir and ritonavir is effective at treating patients with genotype-4 chronic hepatitis C virus (HCV), according to a new report from AbbVie.
Although HCV genotype 4 accounts for only 13% of all HCV infections, it is responsible for more than 90% of HCV infections in Egypt, Dr. Christophe Hézode from Université Paris-Est, Créteil, France, and colleagues write in The Lancet, online March 31.
There are limited data on the effects of direct-acting antiviral drugs in patients with HCV genotype-4 infection, they add.
In the PEARL-I open-label trial, 86 treatment-naïve patients with genotype-4 HCV without cirrhosis were randomly assigned to receive the three-drug combination regimen with or without ribavirin; in addition, 49 treatment-experienced patients were put on the combination treatment with ribavirin.
Sustained virological response rates at 12 weeks were 100% for treatment-naïve patients in the ribavirin-containing regimen, 90.9% for treatment-naïve patients in the ribavirin-free regimen, and 100% for treatment-experienced patients.
There were no relapses between post-treatment week 12 and post-treatment week 24, according to the report.
Three treatment-naïve patients -- all subtype 4b, all with resistance-associated variants present at the time of failure, and all treated without ribavirin -- had virological failure.
The most common treatment-emergent adverse events were headache, asthenia, insomnia and nausea.
"Although no difference between the ribavirin-containing and ribavirin-free regimens was noted, the 100% SVR12 rate recorded with the ribavirin-containing regimen in treatment-naïve and treatment-experienced patients suggests that this multitargeted regimen provides the highest certainty of achieving sustained virological response in patients infected with diverse HCV genotype 4 subtypes," the researchers conclude.
Dr. Heiner Wedemeyer from Hannover Medical School in Germany, who wrote a commentary related to the report, told Reuters Health by email that there is no role for interferon in treating HCV infection outside of resource-limited settings.
According to his commentary, "all new direct-acting antivirals have been approved by the European Medicines Agency (EMA) and the US Food and Drug Administration for treatment of HCV genotype 1 infection, whereas only sofosbuvir and daclatasvir can theoretically be used for all seven HCV genotypes, frequently in the absence of clinical trial data."
Dr. Wedemeyer added to Reuters Health that the regimen in the PEARL-I study "will be one of the possible treatment options. There are also other options (ledipasvir/sofosbuvir or daclatasvir/sofosbuvir; theoretically simeprevir/sofosbuvir)."
Dr. Imam Waked from National Liver Institute in Shebeen El-Kom, Egypt, told Reuters Health, "This study was on non-cirrhotic patients, and efficacy in cirrhotic patients with genotype 4 infection (both treatment-naïve and -experienced) is still not known. An ongoing trial in Egypt will answer this question (it includes patients with cirrhosis, both treatment-naïve and previous treatment failures). The better response in the ribavirin containing arms will not allow this to become a ribavirin-free regimen."
"There is no longer any role for interferon in treating HCV infection," Dr. Waked agreed with Dr. Wedemeyer. "Only where new treatments are not available should interferon-based treatment be used."
"Access programs by Gilead and Johnson & Johnson have made their similar medications (sofosbuvir and simeprevir) available for Egypt to treat patients, and currently 40,000 patients have started treatment on the account of the Ministry of Health (100% state-covered)," Dr. Waked added.
Dr. Hézode, who has been a speaker and a consultant for AbbVie, the trial's sponsor, did not respond to a request for comments. AbbVie employed a number of his co-authors and also paid for writing assistance in preparing the report.