DAAs safer, more tolerable than interferon for HCV infections


Researchers find that direct-acting antivirals are better tolerated in patients with hepatitis C virus infections vs. interferon-based therapy.

Direct-acting antivirals (DAAs) are much safer and more tolerable in the treatment of chronic hepatitis c virus (HCV) infections than interferon-based therapies, according to a new review of adverse events.

The discovery and development of DAAs heralded a marked improvement in rates of sustained virological response as well as quality of life for HCV patients. New anti-viral agents have been evaluated as add-on therapies to pegylated interferon and ribavirin or, more recently, as all-oral DAA combination regimens. This has virtually eliminated interferon-based therapy from HCV management, senior author K. R. Reddy, MD, of the Hospital of the University of Pennsylvania, told Medical Economics.

“This review article provides an overview of the reported adverse events with the current and former HCV therapies,” Reddy said.

After searches of PubMed and FDA surveillance studies, the reviewers characterized the burden of the most clinically significant adverse events associated with DAAs in combination therapy, either with or without interferon and ribavirin.

The reviewers published their results in March 2016 Alimentary Pharmacology & Therapeutics.

DAAs are “remarkably well tolerated,” Reddy said, but they are accompanied by unique adverse events. Simeprevir, an NS3/4A protease inhibitor, has been known infrequently to cause mild hyperbilirubinemia and photosensitivity reactions. Paritaprevir boosted with ritonavir causes bilirubin and ALT elevations. Asunaprevir, another protease inhibitor, infrequently causes elevated transaminase levels.

Asunaprevir, most frequent used in combination with daclatasvir, has a favorable adverse event profile in patients with genotype 1 HCV infection. The drawbacks of asunaprevir include risk of elevated liver enzymes and other limitations characteristic of protease inhibitors, he said.


NS5A and NS5B inhibitors are also well tolerated, although he noted that sofosbuvir is contraindicated in patients with severe renal impairment. Ribavirin co-administered in certain treatment regimens has been associated with cough, rash and hemolytic anaemia.

Preliminary results of elbasvir and grazoprevir are promising, Reddy said, and this regimen is effective and tolerable with no unique adverse events reported, regardless of the treatment duration or setting of compensated cirrhosis.

“It is too early to say how the clinical profiles of second-wave anti-viral agents compare to current DAAs,” said Reddy. “We need more clinical trial data and real-life data. Also, there is a lack of head-to-head comparisons.”

He noted that there are multiple adverse events from DAAs, but, in general, they are of mild intensity. For example, simeprevir may cause adverse skin reactions, but they rarely lead to withdrawal from therapy.

The development of DAAs “has led to a new treatment paradigm for HCV-infected patients,” said Reddy. Landmark clinical trials have demonstrated that combinations of NS3/4A protease inhibitors, NS5A inhibitors, and NS5B inhibitors attenuate adverse events associated with pegylated-interferon plus ribavirin therapy and significantly shorten treatment duration.

“Current DAAs are much better tolerated in comparison with interferon-based therapy,” said Reddy. He noted that data from several phase II and III clinical trials show that various DAA therapies are “well tolerated in both treatment-naïve and treatment-experienced patients with compensated or decompensated cirrhosis, with no more than 10% of patients undergoing treatment experiencing serious adverse events.”

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