Review: Antiviral Medications for Nonsevere Influenza
There are a lack of data available on the optimal antiviral medication for nonsevere flu.
Among available antiviral medications to treat nonsevere influenza, baloxavir is most likely to reduce the risk of hospital admission for high-risk patients, as well as reducing the time to symptom alleviation, according to research results published in JAMA Internal Medicine.1
Because there is a lack of clarity on the optimal antiviral medication to treat nonsevere flu, researchers conducted a systematic meta-review and network analysis to compare available antiviral medications.
Initial search yielded 11,878 studies for potential inclusion; ultimately, 73 unique randomized controlled trials were included. These trials were published between 1971 and 2023 and evaluated 8 antiviral drugs: baloxavir, favipiravir, laninamivir, oseltamivir, peramivir, umifenovir, zanamivir, and amantadine. Sixty-five of these trials included patients within 2 days of symptom onset, and patient sample sizes ranged from 14 to 3266, with a total of 34,332 patients included (median of mean age, 35 years; median proportion of men, 49.8%). Patient follow up ranged from 5 to 29 days.
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A total of 41 trials inclusive of 23,892 patients reported on patient mortality. With a high certainty of evidence, these trials showed that vs standard of care or placebo, 7 antiviral drugs—baloxavir, favipiravir, laninamivir, oseltamivir, peramivir, umifenovir, and zanamivir—had little or no effect on mortality in either low- or high-risk patients (risk difference [RD], -0.12 to 0.02 and -1.22 to -0.24 per 1000 low- or high-risk patients, respectively).
A total of 28 trials inclusive of 17,262 patients reported hospital admission for all antivirals exclusing peramivir and amantadine. Among low-risk patients, there was little or no difference between 6 of the antiviral drugs and standard of care or placebo (baloxavir, favipiravir, laninamivir, oseltamivir, umifenovir, and zanamivir; RD, -2 to 1 per 1000 patients). Among high-risk patients, when compared with standard of care or placebo, baloxavir may have reduced hospital admission risk, while oseltamivir and zanamivir had little or no effect.
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Two trials inclusive of 1626 patients had data on ICU admission for oseltamivir and peramivir. When compared with either standard of care or placebo, oseltamivir had little or no effect on ICU admission (RD, -2 per 1000 patients). Investigators noted that they remain “uncertain whether peramivir reduced admission to the ICU.”
A total of 59 trials with 24,086 patients reported time to symptom alleviation. When compared with standard of care or placebo, baloxavir and umifenovir demonstrated a mean difference of 1.02 and 1.10 days shorter symptom duration, while oseltamivir and zanamivir had mean decreases in symptom duration of less than 1 day.
Hospitalization was evaluated in 3 trials with 234 patients who received oseltamivir, peramivir, and zanamivir. Evidence, the investigators noted, “was very uncertain as to whether these drugs reduced duration of hospitalization.”
In total, 49 trials with 22,868 patients reported data on overall adverse events. When compared with standard of care or placebo, baloxavir did not increase overall adverse events; zanamivir “may not have” resulted in an increase. Thirty-six trials with 19,298 patients reported adverse event data related to treatments. Compared with standard of care or placebo, baloxavir did not increase treatment-related adverse events, while oseltamivir likely increased these events.
Twelve trials with a total of 1554 patients reported emergence of resistance for patients receiving antiviral drugs. Baloxavir in particular “may have had an important impact on emergence of drug resistance), and investigators were “uncertain whether oseltamivir and peramivir increased emergence of drug resistance.”
Study limitations include limited evidence for some antiviral drugs and outcomes, low event rates for some patient-reported outcomes, and a lack of data on outcomes such as progression to mechanical ventilation, duration of mechanical ventilation, and hospital discharge duration, among others.
“This systematic review and meta-analysis found that baloxavir probably reduced risk of hospital admission for high-risk patients and may reduce time to alleviation of symptoms, without increasing adverse events related to treatment in patients with nonsevere influenza,” the investigators concluded. “All other antiviral drugs either probably have little or no effect, or uncertain effects on patient-important outcomes.”
READ MORE: Influenza Resource Center
