August 4, 2009

Which Flu Drug Works Best?

Countries around the world are stockpiling two common anti-influenza drugs -- Relenza and Tamiflu -- for possible use in the current H1N1 flu pandemic, as well as for future influenza pandemics.

In response to this recent phenomenon, researchers from the Stanford University School of Medicine pooled and analyzed data from seven previously published studies, which showed these two drugs appear equally effective at preventing flu symptoms when given before infection, although neither drug has been shown to prevent infection. Moreover, say researchers, data is lacking on the effectiveness and safety of the two drugs in vulnerable groups such as the very young and people with compromised immune systems.

Relenza and Tamiflu are best known for their ability to reduce or shorten flu symptoms in already-infected individuals. The studies, published between 1999 and 2007, indicated individuals treated with either drug were less likely to develop symptomatic influenza -- that is, both to test positive for influenza infection and to experience symptoms like fever, headache, muscle aches and coughing -- than did those who had received a placebo. Those who received the drugs were, however, no less likely to become infected.

Three studies investigated the effectiveness or safety of Relenza, and the four others explored the effectiveness and safety of Tamiflu. None of the studies compared the two drugs with each other, and all of the studies were funded by pharmaceutical manufacturers. Six of the seven studies included authors that had served as paid consultants of the sponsoring pharmaceutical company.

"These are still high-quality studies," Stanford pulmonologist and critical care specialist Nayer Khazeni, MD, lead author of the study was quoted as saying, "but we always like to see research that is independently funded, and we don't have that in this case."

Khazeni added: "There's a paucity of data for children and people with weakened immune systems, even though they've been identified by the Department of Health and Human Services and other public health agencies as priority groups in an influenza pandemic. We were hoping to find a much broader distribution of participants in the studies."

In general, the two drugs appeared to be relatively well-tolerated, although there was increased risk of nausea and vomiting in individuals receiving Tamiflu, especially in those receiving higher-than-recommended preventive doses. None of the studies enrolled enough people to detect the extremely rare events, including neurological and psychological disorders, which have been associated with these antiviral drugs in certain ethnic and age groups.

Khazeni outlined further limitations of the studies. "Nearly all the participants were Caucasian, with the exception of one study of Japanese adults. Children under 12 years of age were not studied, nor were immune-compromised adults or people who had received the live-attenuated influenza virus vaccine."

Live-attenuated vaccine is delivered in the form of an inhaled nasal spray and is increasingly used as an alternative to the more familiar injected vaccine, especially in children.

Khazeni further noted that although the authors performed a thorough search of studies published in all languages, it is possible there were studies, as yet unpublished, that did not replicate these findings.

Because Relenza appears prevent symptoms as effectively as Tamiflu, it may be useful in combating the increasing number of cases of Tamiflu-resistant influenza observed worldwide. Still, Relenza is not recommended for people with preexisting lung conditions, as it is inhaled as a powder rather than taken orally.

Although administering the drugs to uninfected people may lessen the chance of symptoms after infection, it is not yet known whether asymptomatically infected people can still transmit the disease. Khazeni and colleagues are creating mathematical model of a hypothetical influenza pandemic in New York City in which extended administration of this class of anti-influenza medications is one strategy used to prevent infection.

SOURCE: Annals of Internal Medicine, August 4, 2009