Antivirals have little to no effect on nonsevere influenza, review indicates
A systematic review and meta-analysis of 73 trials assessing effects of antivirals in outpatients with influenza found that baloxavir was the only drug that appeared to potentially benefit high-risk patients, although it may also contribute to drug resistance.
Baloxavir may be superior to standard care or placebo in reducing the risk of hospital admission for high-risk patients with nonsevere flu and likely decreases time to alleviation of symptoms with few or no adverse effects, according to results of a systematic review and meta-analysis.
To compare the effects of antiviral drugs to treat nonsevere flu, researchers searched online databases for randomized clinical trials that compared direct-acting influenza antiviral drugs (baloxavir, favipiravir, laninamivir, oseltamivir, peramivir, umifenovir, zanamivir, and amantadine) to placebo, standard care, or another antiviral drug. Outcomes included mortality, hospital admission, ICU admission, duration of hospitalization, time to symptom alleviation, emergence of resistance, and adverse events. A total of 73 trials with 34,332 participants were included in the study. Findings were published by JAMA Internal Medicine on Jan 13.
The researchers' analyses showed that all antiretroviral drugs had little or no effect on mortality for low-risk and high-risk patients with flu compared with standard care or placebo (high certainty for all drugs). All drugs also had little or no effect on hospital admission for low-risk patients (high certainty), with the exception of peramivir and amantadine, for which no data were available. In high-risk patients, baloxavir may have reduced the risk of admission (risk difference [RD], −1.6%; 95% CI, −2.0% to 0.4%; low certainty), oseltamivir had little or no effect on hospital admission (RD], −0.4%; 95% CI, −1.0% to 0.4%; high certainty), and all other drugs may have had little or uncertain effects. In addition, baloxavir probably reduced symptom duration (mean difference [MD], −1.02 days; 95% CI, −1.41 to −0.63 days; moderate certainty) and umifenovir may have reduced symptom duration (MD, −1.10 days; 95% CI, −1.57 to −0.63 days; low certainty). Oseltamivir probably had no important effect on time to symptom alleviation (MD, −0.75 day; 95% CI, −0.93 to −0.57 days; moderate certainty). Baloxavir also had few or no adverse events related to treatment (RD, −3.2%; 95% CI, −5.2% to −0.6%; high certainty) and oseltamivir probably increased adverse events, primarily nausea and vomiting (RD, 2.8%; 95% CI, 1.2% to 4.8%; moderate certainty). Baloxavir may have resulted in resistance in around 10% of patients treated.
Researchers cautioned that the evidence for some antiviral drugs and some outcomes was limited and that many included trials may have lacked the power to detect certain patient outcomes, including mortality and hospitalization.
“Our findings support the use of baloxavir for treatment of high-risk patients with nonsevere influenza. However, drug resistance monitoring may be needed because baloxavir may increase emergence of drug resistance,” they concluded.
In an accompanying editorial, authors noted they were surprised to find antivirals seemed to make little difference for individuals with influenza in outpatient settings.
Given the evidence, “we are left to wonder why reflexive treatment of influenza with oseltamivir has become so ingrained in clinical practice,” they wrote. “The accumulating evidence indicates that the time has come for clinicians and health care systems to reconsider their basic approach to outpatients with influenza,” the editorialists concluded.