Study Questions Long-Term Outcomes of Direct-Acting Antivirals in Treating Hepatitis C

JUNE 16, 2017
Gail Connor Roche


While direct-acting antiviral (DAA) drugs may clear the hepatitis C virus from a patient’s blood, a new report questions whether the medications eliminate HCV in the body, improve survival or result in fewer complications from the liver-attacking disease.
           
The Cochrane organization, which describes itself as a global independent network of researchers, professionals and patients, reviewed 138 randomized clinical trials of DAA drugs. The studies covered 25,232 participants and assessed the effects of 51 different DAAs. Cochrane published its findings on June 6.
 
 “DAAs do not seem to have any effects on the risk of hepatitis C-related morbidity or all-cause mortality,” according to the review led by Janus C. Jakobsen, MD, PhD and deputy coordinating editor at the Cochrane Hepato-Biliary Group’s Copenhagen Trial Unit. “In fact, there were no data on hepatitis C-related morbidity and very few data on mortality” in the studies that Cochrane assessed.
 
The World Health Organization estimates that 1.75 million people were first infected with HCV in 2015, bringing the global total to 71 million. Almost 400,000 individuals die each year from the virus, mostly from cirrhosis and hepatocellular carcinoma, or liver cancer, the WHO said in April.
 
DAAs are relatively new and expensive pills developed to treat chronic HCV. The medications have been lauded for their ability to cure patients by producing sustained virologic response (SVR), or an absence of detectable HCV RNA in the blood. DAAs have better success rates, act more quickly and produce fewer side effects than previous treatments, recent studies have found.
 
Cochrane researchers set out to assess the benefits and harms of DAAs in people with chronic HCV by reviewing existing trials. Most of the studies (128) included use of a placebo in the control group. Eighty-four involved DAAs on the market or under development covering 13,466 participants, while 57 trials were conducted on drugs that had been withdrawn from the market.
 
The trials were held from 2004 to 2016 in 34 different countries. The intervention periods ranged from one day to 48 weeks with an average of 14 weeks. The combined intervention and follow-up periods were one day to 120 weeks with an average of 34 weeks, according to the report.
 
Cochrane’s analysis of all DAAs on the market or under development showed no evidence of producing any difference when assessing morbidity, mortality or serious adverse events. When analyzed separately, the only DAA that exhibited evidence of a beneficial effect in its risk of a serious adverse event was simeprevir (Olysio, Janssen Therapeutics), according to the report.
 
While most of the trials primarily investigated the effects of DAAs on sustained virologic response, Cochrane said it’s questionable if SVR has any clinical relevance to a person with chronic hepatitis C.
 
 “Outcome results were short-term results; therefore, we could neither confirm nor reject any long-term effects of DAAs,” the researchers wrote.
 
The organization cited the “high risk of bias” in the trials, which were largely conducted by drug companies developing DAAs. The researchers also said that the quality of evidence in the trials was “low.”
 
“The lack of valid evidence and the possibility of potentially harming people with chronic hepatitis ought to be considered before treating people with hepatitis C with DAAs,” the authors concluded.
 
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