Wednesday, January 21, 2015

Are treatment recommendations for influenza evidence-based?

- Kenny Lin, MD, MPH

As the Centers for Disease Control and Prevention (CDC) reported that people who received this season's influenza vaccine were only 23 percent less likely to be diagnosed with influenza than unvaccinated persons, CDC director Tom Frieden was publicly urging high-risk patients and their physicians to use antiviral medications to prevent complications and disease transmission:

People who are sick with flu, if they're very sick in the hospital or if they have underlying, chronic medical conditions, like asthma, diabetes, heart disease, women who are pregnant, children under two and people over the age of 65 - all of these people, if they get flu, should get treated with antiviral drugs. The evidence indicates that it will shorten how long you're sick, might keep you out of the hospital and could even save your life. ... There is some evidence that suggests that taking antiviral medications may reduce the risk that you'll spread the disease to others in your family so it may be helpful for others as well as for yourself.

A previous AFP Community Blog post discussed a 2012 Cochrane review which cast doubt on the ability of the neuraminidase inhibitors oseltamivir and zanamivir to prevent influenza transmission, noting that after including data from unpublished, industry-sponsored, randomized controlled trials, the difference was not statistically significant.

Also in that year, a meta-analysis by AFP Deputy Editor Mark Ebell and colleagues concluded: "There is no evidence that oseltamivir reduces the likelihood of hospitalization, pneumonia or the combined outcome of pneumonia, otitis media and sinusitis." The authors noted that two large unpublished trials of oseltamivir in older persons and persons with chronic disease did not even show that the drug reduced the duration of symptoms, suggesting that oseltamivir might be less effective at treating influenza in high-risk groups.

In 2014, after gaining access to the complete clinical study reports from the manufacturers, the Cochrane Collaboration updated its previous review and drew the following conclusions: "Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children." Taking either of the drugs did not reduce hospitalizations or serious complications, but did increase risk of nausea, headaches, and psychiatric symptoms. The CDC responded that their recommendations for antiviral medications "remained unchanged," arguing that observational studies not considered in the Cochrane review supported prescribing neuraminidase inhibitors for high-risk patients with influenza.

The bottom line for family physicians is that at best, antiviral medications for influenza have modest benefits that need to be balanced against potential adverse effects in deciding whom to treat. Also, existing evidence does not support the CDC's contention that antivirals are more likely to be beneficial in high-risk populations.