February 28, 2012
Review of antivirals as influenza treatment shows benefits
Hamilton, Ont. February 28, 2012—After conducting an extensive review of scientific studies, McMaster University researchers have found antiviral drugs for influenza treatment may provide clinical benefits, especially when neuraminidase inhibitor treatment is started as early as possible.
The findings indicate that oral oseltamivir treatment of influenza may provide net benefit by reducing mortality, the duration of symptoms and complications of influenza.
However, the scientists have also found confidence in the drugs’ effects is limited by the available data from the studies. Researchers systematically reviewed observational studies for the benefits and harms in treating influenza with oseltamivir, zanamivir, amantadine and rimantadine.
They concluded oral oseltamivir and inhaled zanamivir “may provide a net benefit over no treatment for influenza.” However, they cautioned they had limited confidence in some studies because they felt they were biased or lacked necessary evidence.
The review has been published in the Annals of Internal Medicine.
Influenza is a serious global public health issue. The World Health Organization (WHO) estimates approximately a billion cases of influenza occur annually along with three-to-five million cases of severe illness and 300,000 to 500,000 deaths. One study reported that, of an estimated 90 million influenza cases in children under five years of age in 2008, there were approximately 28,000 to 111,500 influenza-associated lower respiratory tract deaths. In the U.S., an estimated average of 200,000 hospitalizations and 3400 to 49,000 influenza-related deaths occur each year.
The McMaster researchers, collaborating with colleagues from Norway and the U.S. Centres for Disease Control and Prevention (CDC), summarized evidence from 74 observational studies about the drug treatment of influenza with antivirals.
Their meta-analyses suggest oral oseltamivir, compared to no treatment, may reduce death in high-risk groups, hospitalizations and lessen the duration of symptoms. They also said that earlier treatment with oral oseltamivir was generally associated with better outcomes. Inhaled zanamivir may lead to shorter duration of symptoms and fewer hospitalizations but more complications than no treatment, the researchers found.
While more research has been conducted on oral oseltamivir, they could not demonstrate important differences between oral oseltamivir and inhaled zanamivir based on existing studies. The researchers acknowledge most cases of influenza don’t last long and may be prevented with annual influenza vaccination. However, oral oseltamivir or inhaled zanamivir are currently used to reduce signs and symptoms and to prevent hospitalizations or deaths in patients with severe disease.
“For some patient-important health outcomes, the best currently available evidence comes from observational studies that we summarized in this systematic evaluation of the available research,” said lead author Dr. Holger Schunemann. He is chair of the Department of Clinical Epidemiology and Biostatistics and a professor of medicine in the Michael G. DeGroote School of Medicine at McMaster University.
Schunemann said other concerns about the clinical trials are based, in part, on the lack of precision about the effect estimates, the lack of evidence for certain patient-important health outcomes such as death, and poor assessment and lack of complete reporting of other outcomes, including for adverse events.
He said questions also remain about the effects of antiviral agents to treat influenza A or B and for specific groups of people, such as hospitalized or immunocompromised patients because not many studies have been conducted among these populations.
“The data in this review indicate that oral oseltamivir and inhaled zanamivir may provide a net benefit over no treatment for influenza,” said Schunemann. “However, as for the randomized clinical trials, the confidence in the estimates of the effects for decision-making is low to very low and better research is still needed.” He calls for what he calls clinical trial preparedness; and that health organizations should be ready to roll out large trials during influenza epidemics or pandemics.
Dr. Tim Uyeki, of the Influenza Division of the CDC, and a co-author of the report, emphasized that despite the limitations of these studies and others published since 2010, they have consistently found that starting neuraminidase inhibitor treatment within 48 hours of illness onset in influenza patients provides the greatest clinical benefit. But, starting antiviral treatment later may still provide some benefit, including for hospitalized influenza patients.
Dr. Uyeki emphasized that patients who are at high risk for complications from influenza, such as young children, pregnant women, elderly, persons with underlying chronic medical conditions, who have acute respiratory illness should be encouraged to seek medical evaluation quickly during influenza season and that clinicians should start antiviral treatment with oral oseltamivir or inhaled zanamivir as soon as possible if influenza is confirmed or suspected. He also said that hospitalized patients with confirmed or suspected influenza should be treated as soon as possible and that they receive appropriate management of any complications.
Uyeki also said that better antiviral treatment options need to be developed, especially drugs with different mechanisms of action, and new treatment strategies are needed, including combination therapy.
The research was funded by the World Health Organization and McMaster University.
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Veronica McGuire
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