tetano
Editor, Senior Moderator
Open Forum Infect Dis
. 2025 Jul 25;12(8)
faf439.
doi: 10.1093/ofid/ofaf439. eCollection 2025 Aug. Effects of Baloxavir Marboxil Plus Neuraminidase Inhibitor vs Neuraminidase Inhibitor in High-risk Patients Hospitalized With Severe Influenza: A Post Hoc Analysis of the Flagstone Trial
Mengwei Yan[SUP] 1 2 [/SUP], Xiaoying Gu[SUP] 2 [/SUP], Yeming Wang[SUP] 1 2 [/SUP], Bin Cao[SUP] 1 2 3 [/SUP]
Affiliations
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.
Keywords: baloxavir; dual antiviral therapy; high-risk; post hoc analysis; severe influenza.
. 2025 Jul 25;12(8)
faf439.doi: 10.1093/ofid/ofaf439. eCollection 2025 Aug. Effects of Baloxavir Marboxil Plus Neuraminidase Inhibitor vs Neuraminidase Inhibitor in High-risk Patients Hospitalized With Severe Influenza: A Post Hoc Analysis of the Flagstone Trial
Mengwei Yan[SUP] 1 2 [/SUP], Xiaoying Gu[SUP] 2 [/SUP], Yeming Wang[SUP] 1 2 [/SUP], Bin Cao[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 40852135
- PMCID: PMC12368417
- DOI: 10.1093/ofid/ofaf439
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.
Keywords: baloxavir; dual antiviral therapy; high-risk; post hoc analysis; severe influenza.