Influenza
Terri D’Arrigo
Antiviral medications do not make a difference in mortality or admission to the hospital in patients with nonsevere influenza, according to a systemic review and meta-analysis published on January 13, 2025, in JAMA Internal Medicine. However, the analysis suggested that baloxavir may slightly reduce the risk of hospital admission for high-risk patients and may reduce time to alleviation of symptoms.
Researchers at Shandong University, Jinan, China, and colleagues analyzed data from 73 trials published from 1971 through 2023, encompassing 34,332 participants. The studies in the analysis were randomized controlled trials that compared direct-acting influenza antiviral drugs to no intervention, placebo, standard care, or another antiviral drugs for individuals with suspected or laboratory-confirmed flu.
The researchers defined severe illness from flu as requiring hospitalization and nonsevere flu as the absence of any criteria for severe flu.
The studies in the analysis assessed mortality, admission to hospital, admission to the ICU, duration of hospitalization, time to alleviation of symptoms, emergence of resistance, any adverse events, and other measurements. The researchers defined time to alleviation of symptoms as time from the start of treatment to the improvement of all influenza-associated symptoms.
Compared with standard care or placebo, all of the antiviral medications had little or no effect on mortality for either low- or high-risk patients. For low-risk patients, there was little or no difference between six out of nine of the medications and standard of care or placebo.
For admission to hospital in high-risk patients, compared with standard care or placebo, only one medication (i.e., baloxavir) may have reduced risk at a rate of 16 fewer hospitalizations per 1,000 patients, although the certainty of evidence was low.
Patients who took baloxavir had a mean decrease in symptom duration of 1.02 days compared with those who had standard care or placebo, with a moderate certainty of evidence. However, baloxavir may have been associated with the emergence of resistance in approximately 10% of patients who were treated with it.
Those who took oseltamivir and zanamivir had a mean decrease in symptom duration of less than 1 day with moderate certainty of evidence.
No surprises here
Marilyn N. Bulloch, PharmD, associate clinical professor and the director of strategic operations at Harrison College of Pharmacy at Auburn University, who was not involved in the research, said she was not surprised by the results.
“I wouldn’t expect most of the people in these trials to be at risk of dying if their flu was not severe, so a change in mortality with the use of antivirals is not something I would expect in that population,” she said. “It’s common sense.”
That does not mean these medications should not be used, Bulloch said.
“We prescribe antivirals because the symptom burden of the flu is heavy. It makes people miserable,” she said. She added that improvement of all symptoms is not a strong barometer of effectiveness. “That means 100% back to baseline, but a lot of studies look at other outcomes that are just as important, like how long it is before patients are afebrile or when they started feeling better. When you look at individual studies, the curve of when you start feeling better is much sharper compared to no treatment.”
“We also know that antivirals decrease viral shedding, which is extremely important in communities because it decreases transmission of the virus,” Bulloch said.
“Based on this study, if you have an older patient or a patient with comorbidities, a history of hospitalization, or a lot of medications, you might lean a bit more to baloxavir, as long as the patient can afford it,” she said. “But I would only say that with the caveat that we need to do head-to-head trials to really see what the differences are between antivirals, especially in high-risk patients.” ■