2025/07/25 by Mengwei Yan, Xiaoying Gu, Yeming Wang +1 · 1 voice
Medicine · #Influenza Virus Research Studies #Respiratory viral infections research #Pneumonia and Respiratory Infections
paper · pdf · doi:10.1093/ofid/ofaf439
openalex publication_date 2025/07/25 · openalex created_date 2025/07/29 · openalex updated_date 2026/07/29
Abstract Background Combining baloxavir with neuraminidase inhibitors (NAIs) has not demonstrated significant benefits in severe influenza. High-risk populations with impaired viral clearance may represent the optimal candidates for this combination treatment. Methods We conducted a post hoc analysis of the Flagstone trial (NCT03684044), including patients hospitalized with severe influenza. Eligible participants met at least 1 of the following criteria: immunosuppression, diabetes, or chronic lung disease. Time to clinical improvement (TTCI), 28-day mortality, virological outcomes, and safety end points were assessed. Results Among the 143 patients included in the efficacy analysis, 92 received baloxavir in combination with NAI (dual antiviral group), while 51 received NAIs alone (mono antiviral group). The median TTCI did not differ significantly between groups (P = .48). However, in patients infected with influenza A H3N2, the TTCI was significantly shorter in the dual compared with the mono antiviral group (median [interquartile range IQR], 97.53 [43.02–149.27] hours vs 172.42 [95.93–243.52] hours; P = .013). The dual antiviral group demonstrated significantly lower mortality compared with the mono antiviral group (2 [2.17%] of 92 vs 6 [11.76%] of 51; P = .02) and was associated with a shorter time to cessation of viral shedding (P < .001). A significantly greater reduction in the adjusted mean change in virus titer from baseline to day 2 was observed in the dual antiviral group (P < .001). Serious adverse events were comparable between the 2 groups (P = .42). Conclusions The combination of baloxavir and NAI demonstrated superior mortality reduction compared with NAI monotherapy, without increasing the risk of adverse events.