TORONTO - Antiviral drugs can significantly cut the risk of death for older adults hospitalized with severe cases of influenza, even if the therapy is started outside the optimal treatment window, a new study from Toronto researchers suggests.
People stricken with a case of flu so severe it sent them to hospital were five times less likely to die if they were put on antiviral therapy compared to those who didn't receive one of these drugs, the study found.
The findings could alter the way doctors treat hospitalized flu patients, experts who were not involved with the study said.
"I think and talk about flu a lot. And this is going to change what I say," said Dr. Anne Moscona, an infectious diseases expert at Weill Cornell Medical Center in New York City.
"I think this could be a real advance."
The findings were particularly striking because the bulk of the treated patients were started on the antiviral drugs more than 48 hours after the onset of their symptoms.
The studies used to win regulatory approval for the newer flu drugs showed they were of little benefit after 48 hours. But those studies were done in otherwise healthy adults whose immune systems would have kicked in to halt the replication of the virus by that point, setting them on the road to recovery.
But this work suggests older people and people whose immune systems can't easily combat the flu virus can benefit from treatment past the 48-hour cut-off.
"It's clear from this experience now that there seems to be benefit even with later treatment," Dr. Frederick Hayden, an antiviral expert with the World Health Organization's global influenza program, said from Geneva.
Hayden said the study will "add to the body of evidence . . . that hospitalized patients warrant therapy if there's evidence for ongoing (virus) replication."
The study evaluated what happened to 327 adults who were hospitalized with influenza in a network of south-central Ontario hospitals during the 2004-05 and 2005-06 flu seasons. The work was led by researchers at Mount Sinai Hospital and the University Health Network, both in Toronto.
The research was supported by Hoffman-La Roche, which produces the antiviral drug oseltamivir, sold as Tamiflu. It will be published in the Dec. 15 issue of Clinical Infectious Diseases.
Lead author Dr. Allison McGeer said the researchers did not randomly select patients to either receive antiviral drugs or not on the belief that withholding drugs shown to be effective against influenza would be unethical.
Instead they followed the testing, treatment and outcome of cases, leaving the decisions about whether to use the drugs up to the treating doctors, said McGeer, head of infection control at Mount Sinai.
Of the 327 adults, the mean age was 77 years of age. And 75 per cent had other health conditions, putting them at greater risk from a bout of flu.
Interestingly, 71 per cent of the adults had been vaccinated against influenza in the year in which they were hospitalized. It's well known that aging weakens the immune system's ability to mount a strong response to flu shots, making the vaccine less effective in the people at highest risk of dying from influenza.
When the patients were admitted, 89 per cent were started on antibiotics, which have no impact on flu, a virus. Only 32 per cent were given antiviral drugs. To be eligible for inclusion in the study, patients had to have tested positive for influenza.
"It is a distinct anomaly that we are treating for infections that we don't know they have but not treating for infection we do know they have," McGeer noted in an interview Tuesday.
In actuality, hospitals often don't test for flu. The available tests have serious limitations and many physicians aren't convinced of the benefits of antiviral treatment - especially when it is started late.
"But when you look at the data with the wisdom of hindsight, it seems logical to say that the reason that you can treat late in people admitted to hospital is that people admitted to hospital with influenza are different than the people who can control it themselves," McGeer said.
"And if you need help controlling viral replication, it won't just be in the first 48 hours."
Moscona said the results suggest more physicians should be testing for influenza and prescribing antiviral treatment when they find it in hospitalized patients.
"If we test more, we'll identify more," she said. "And people will get more antivirals as opposed to antibiotics."
