According to a comprehensive systematic review and network meta-analysis, baloxavir may be the most effective antiviral medication for treating nonsevere influenza, particularly in high-risk patients, while demonstrating a favorable safety profile.

The study, published in JAMA Internal Medicine, analyzed 73 randomized clinical trials involving 34,332 participants. Findings suggest that baloxavir may reduce hospital admission risk in high-risk patients (risk difference [RD], -1.6%; 95% CI, -2.0 to 0.4; low certainty) and likely reduces symptom duration by 1.02 days (mean difference [MD], -1.02 days; 95% CI, -1.41 to -0.63; moderate certainty). In contrast, oseltamivir showed little to no effect on hospital admissions (RD, -0.4%; 95% CI, -1.0 to 0.4; high certainty) and likely reduced symptom duration by 0.75 days (MD, -0.75 days; 95% CI, -0.93 to -0.57; moderate certainty).

"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 researchers wrote.

The analysis, led by Ya Gao, PhD, from Shandong University, evaluated eight antiviral drugs, including baloxavir, favipiravir, laninamivir, oseltamivir, peramivir, umifenovir, zanamivir, and amantadine. Researchers assessed multiple outcomes, such as mortality, hospital admission, ICU admission, symptom duration, and adverse events.

All antiviral medications showed little to no effect on mortality for low- and high-risk patients (high certainty). For adverse events, baloxavir had a favorable profile (RD, -3.2%; 95% CI, -5.2 to -0.6; high certainty) compared to oseltamivir, which likely increased adverse events (RD, 2.8%; 95% CI, 1.2 to 4.8; moderate certainty). Notably, baloxavir may be associated with resistance in approximately 10% of treated patients, though this finding is based on low-certainty evidence.

The study applied the GRADE approach to evaluate evidence systematically, and its inclusion of more trials than prior analyses increases its comprehensiveness. However, the researchers acknowledged limitations, including low event rates for certain outcomes and heterogeneity across studies regarding patient populations, treatment timing, drug doses, and treatment duration. These factors may limit generalizability.

One investigator served as the method chair for the WHO guideline panel and other authors were contractors who contributed to the systematic review and evidence synthesis. No other disclosures reported.