Several oral direct-acting agent regimens effective for HCV infection

Last Updated: 2017-03-21

By Will Boggs MD

NEW YORK (Reuters Health) - Highly effective, well-tolerated oral direct-acting agent (DAA) regimens are now available for all hepatitis C virus (HCV) genotypes and for patient populations historically considered difficult to cure, according to a systematic review of 42 studies.

"We have multiple, highly effective, safe options for hepatitis C treatment and cure,” Dr. Oluwaseun Falade-Nwulia from Johns Hopkins University School of Medicine, Baltimore, Maryland told Reuters Health by email. “As a medical community, we need to expand our hepatitis C testing efforts so that everyone who is infected is aware of their infection. Hepatitis C infected individuals need to be linked to hepatitis C treatment and treatment access expanded.”

Dr. Falade-Nwulia and colleagues systematically reviewed the efficacy and safety of oral interferon-free HCV treatment regimens that include at least 2 DAAs.

Six distinct DAA regimens provided sustained virological response (SVR) rates greater than 95% for genotype 1 infection for most drug combinations and patient populations, according to the March 21st Annals of Internal Medicine online report.

Two DAA regimens, including sofosbuvir plus the NS5A inhibitors velpatasvir or daclatasvir for 12 weeks, are effective for treatment of HCV genotype 3 infection without cirrhosis, and the combination sofosbuvir-velpatasvir offers higher SVR rates in patients with cirrhosis.

For patients with genotype 3 infection, SVR rates were lower in those with compensated and decompensated cirrhosis, prior treatment experience, or NS5A resistance-associated substitutions, whereas SVR rates were higher with the addition of ribavirin and with longer treatment duration.

Only a few studies enrolled patients with genotype 2, 4, 5, or 6, but high rates of SVR (>92%) were observed for all regimens given for at least 12 weeks, and SVR rates were particularly high (99%) among patients treated with velpatasvir-sofosbuvir.

These oral DAA regimens offered high SVR rates with minimal adverse events among patients who were poorly responsive to or could not be treated with interferon, including those with HIV coinfection, decompensated cirrhosis, severe chronic kidney disease, and liver transplant.

Given the multitude of effective oral DAA regimens with similar rates of SVR and adverse events, randomized controlled trials are needed to sort out the best HCV treatments for different patient populations, the researchers note.

“The safety and effectiveness of these drugs has not only expanded the pool of patients that can be cured of hepatitis C, but also makes it possible for providers who have not traditionally treated hepatitis C (e.g., primary care providers) to become hepatitis C treaters,” Dr. Falade-Nwulia said.

Dr. Jay H. Hoofnagle from the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, who wrote an editorial related to this report, told Reuters Health by email, "It is important for the medical community to understand that therapies for hepatitis C have matured and are not going to get significantly better. Treatment is recommended for all patients with chronic hepatitis C infection. Many people do not know that they are infected and those with risk factors should be screened.”

“Currently approved therapeutic options for chronic HCV infection are generally safe and highly effective with short courses of treatment,” he said. “Viral eradication does not completely eliminate the risk of future liver complication, and appropriate follow-up of patients is still required.”

In his editorial, Dr. Hoofnagle notes that “public health messages and television commercials have raised awareness of the benefits of screening, but reaching the populations most likely to harbor HCV will be a challenge. Compounding this problem are the costs of these therapies. The current market prices for available oral regimens in the United States range from $55,000 to more than $150,000. Even with negotiated price discounts, these therapies will remain a considerable burden both to private insurers and to our already fragile public budgets for health care funding.”

Dr. Kurinchi Guruswamy from the Royal Free Hospital and University College London, UK told Reuters Health by email, “The major problem with this review is that the review does not look at important patient measures, such as longevity or quality of life; neither does it look at the proportion of people who developed severe chronic liver disease (cirrhosis) or liver failure (decompensated liver failure).”

SVR, he continued, “is an established prognostic marker, but not a valid surrogate marker of clinical improvement, i.e., people who develop SVR have better outcomes related to longevity of life, cirrhosis, and liver failure, but this develops in particular groups of individuals who have better prognosis. There has been no study showing that altering the SVR using drugs results in improvement in longevity of life, cirrhosis, and liver failure.”

“Physicians should ignore this finding and rely on treatments that make a difference to longevity of life, quality of life, cirrhosis, or liver failure,” Dr. Guruswamy concluded.

A 2013 paper coauthored by Dr. Guruswamy (http://bit.ly/2nxfFdU) concluded that the “SVR threshold at which retreatment increases life expectancy may be different for different drugs depending upon the adverse event profile and treatment efficacy. This has to be determined for each drug by RCTs and appropriate modeling before SVR can be accepted as a surrogate marker.”

Dr. Raymond T. Chung from Massachusetts General Hospital in Boston, who recently reviewed current HCV therapeutic regimens and drug-drug interactions, told Reuters Health by email, "All-oral regimens for hepatitis C virus are effective not only in patients with uncomplicated disease, but also in populations we once considered difficult to treat, including those with HIV coinfection, those with impaired liver or kidney function, and those who have undergone liver transplantation.”

These findings “should alert caregivers to the treatability of all populations of patients infected with HCV,” he concluded.

SOURCE: http://bit.ly/2nFJV6Z

Ann Intern Med 2017.