Major Finding: In the four trials totaling 475 high-risk patients, the rate of flu-related pneumonia, bronchitis, sinusitis, pharyngitis, and other complications was 8% in neuraminidase inhibitor—treated patients, compared with 25% with placebo.
Data Source: A meta-analysis of 11 placebo-controlled randomized trials of oseltamivir or zanamivir.
Disclosures: The meta-analysis was supported by the nonprofit Alfa Institute of Biomedical Sciences. Dr. Falagas reported having no financial conflicts.
VIENNA — It's well established that timely prescription of the neuraminidase inhibitors can reduce the duration of seasonal influenza symptoms.
Now there's good evidence that the drugs are effective in reducing influenza-related complications, too, according to Dr. Matthew Falagas.
A meta-analysis of 11 placebo-controlled randomized trials—10 of them double blind—demonstrated that treatment with oseltamivir (Tamiflu) or zanamivir (Relenza) reduced the overall rate of flu-related complications by 26% in otherwise healthy patients with confirmed seasonal influenza, he reported at the meeting.
The magnitude of benefit was substantially greater in high-risk patients than in those who were previously healthy.
In the four trials totaling 475 high-risk patients, the rate of flu-related pneumonia, bronchitis, sinusitis, pharyngitis, and other complications was 8% in neuraminidase inhibitor–treated patients compared with 25% with placebo—for a 63% relative risk reduction, said Dr. Falagas, director of the Alfa Institute of Biomedical Sciences, Athens.
In the six trials totaling nearly 2,000 subjects in which administration of antibiotics was an end point, treatment with a neuraminidase inhibitor conferred a 23% reduction in the use of antibiotic therapy, Dr. Falagas continued.
The overall reduction in flu-related complications in the group receiving antivirals was driven by a highly significant 50% decrease in the rate of acute otitis media.
Indeed, the number of patients who needed to be treated (NNT) with a neuraminidase inhibitor to prevent one additional case of acute otitis media was 18.
There were consistent albeit weaker trends for lower rates of pneumonia, sinusitis, and the other flu-related complications in neuraminidase inhibitor–treated patients, none of which achieved significance.
For example, the incidence of pneumonia in the placebo group was just 2%, and it was estimated that roughly 330 patients would need to be treated with a neuraminidase inhibitor to prevent one additional case of pneumonia.
Only four trials included mortality as a study end point. There were no deaths.
The 11-trial meta-analysis involved 5,315 randomized patients.
Three of the trials were done in children; the rest were done in adults and adolescents.
The magnitude of risk reduction with neuraminidase inhibitor therapy was similar in children and adults, and with oseltamivir compared with zanamivir.
Whether these meta-analysis results apply to 2009 H1N1 influenza–related complications as well is anybody's guess, in Dr. Falagas's view, because there are as yet no good randomized controlled trials of neuraminidase inhibitors in patients infected with H1N1 flu.
He deemed the safety profile of the drugs to be acceptable.
There were no significant differences between the neuraminidase inhibitors and placebo in the rates or severity of any adverse events.
Although the rate of nausea/vomiting was 13% in the neuraminidase inhibitor–treated patients compared with 6.4% with placebo, this trend fell shy of statistical significance.
There was a 30% reduction in diarrhea with the neuraminidase inhibitors, but again this failed to reach significance.
Of note, none of the trials recorded neuropsychiatric adverse events.
One audience member observed that in February the World Health Organization recommended that the neuraminidase inhibitors generally be reserved for high-risk patients in the setting of H1N1 flu.
Does this new meta-analysis argue for using the drugs in otherwise healthy patients as well? he asked.
Not really, Dr. Falagas replied.
The observed overall significant reduction in flu-related complications occurred as a result of the sharp drop in acute otitis media, which “is not a killer disease,” he said.
There was no significant reduction in the far more serious complication of pneumonia and no apparent treatment impact upon mortality.
It's thus quite reasonable in Dr. Falagas's view to save these fairly costly drugs for high-risk patients, thereby minimizing problems with the development of antiviral resistance.
“Our data are not in disagreement with the WHO recommendation that neuraminidase inhibitors are best for high-risk patients,” the physician stressed.
The magnitude of benefit was substantially greater in high-risk patients.
Source DR. FALAGAS