A network meta-analysis of the efficacy and safety of baloxavir marboxil versus neuraminidase inhibitors for the treatment of influenza in otherwise healthy patients

Abstract

Objective: Baloxavir marboxil (baloxavir) is the first cap-dependent endonuclease inhibitor being studied for the treatment of influenza in single oral dosing regimen. This network meta-analysis (NMA) evaluated the efficacy and safety of baloxavir compared to other antivirals for influenza in otherwise healthy patients. Methods: A systematic literature review was performed on 14 November 2016 in Medline, Embase, CENTRAL, and ICHUSHI to identify randomized controlled trials assessing antivirals for influenza. A NMA including 22 trials was performed to compare the efficacy and safety of baloxavir with other antivirals. Results: The time to alleviation of all symptoms was significantly shorter for baloxavir compared to zanamivir (difference in median time 19.96 h; 95% CrI [3.23, 39.07]). The time to cessation of viral shedding was significantly shorter for baloxavir than zanamivir and oseltamivir (47.00 h; 95% CrI [28.18, 73.86] and 56.03 h [33.74, 87.86], respectively). The mean decline in virus titer from baseline to 24 h was significantly greater for baloxavir than for the other drugs. Other differences in efficacy outcomes were not significant. No significant differences were found between baloxavir and the other antivirals for safety, except total drug-related adverse events where baloxavir demonstrated a decrease compared to oseltamivir and laninamivir. Conclusions: The NMA suggests that baloxavir demonstrated better or similar efficacy results compared to other antivirals with a comparable safety profile. Baloxavir led to a significant decrease in viral titer versus zanamivir, oseltamivir and peramivir and decreased viral shedding versus zanamivir and oseltamivir.

Efficacy and safety of baloxavir marboxil versus neuraminidase inhibitors in the treatment of influenza virus infection in high-risk and uncomplicated patients – a Bayesian network meta-analysis

“…These results are consistent with previous findings reported in the NMA on OwH patients conducted by Taieb et al showing that baloxavir was more effective than other antivirals regarding the reduction of viral titer within 24 hours. Interestingly in the OwH population, baloxavir was more effective than zanamivir in the alleviation of influenza symptoms, which was not confirmed among the HR population [15].…”

“…The mean decline in virus titer from the baseline at 24h after treatment was significantly greater for baloxavir than for other drugs [15]. Baloxavir demonstrated a comparable safety profile to other antivirals, except for total drug-related adverse events (DRAE) where it demonstrated a decrease compared to oseltamivir and laninamivir [15].…”

“…Baloxavir compared with the placebo reduced the frequency of influenza-related complications (2.8% and 10.4%) and the need for systemic antibiotic use (3.4% vs 7.5%) [14]. A recent network meta-analysis by Taieb et al demonstrated that in the otherwise healthy (OwH) population, baloxavir was associated with a reduced time to alleviation of all symptoms compared to zanamivir, whereas time to cessation of viral shedding was significantly shorter for baloxavir than zanamivir and oseltamivir [15]. The mean decline in virus titer from the baseline at 24h after treatment was significantly greater for baloxavir than for other drugs [15].…”

“…A recent network meta-analysis by Taieb et al demonstrated that in the otherwise healthy (OwH) population, baloxavir was associated with a reduced time to alleviation of all symptoms compared to zanamivir, whereas time to cessation of viral shedding was significantly shorter for baloxavir than zanamivir and oseltamivir [15]. The mean decline in virus titer from the baseline at 24h after treatment was significantly greater for baloxavir than for other drugs [15]. Baloxavir demonstrated a comparable safety profile to other antivirals, except for total drug-related adverse events (DRAE) where it demonstrated a decrease compared to oseltamivir and laninamivir [15].…”

Baloxavir treatment of ferrets infected with influenza A(H1N1)pdm09 virus reduces onward transmission

“…In a recent clinical trial, oral BXM treatment resulted in a 3.5 log 10 TCID 50 /ml reduction in viral shedding at 24 hours post-treatment, whereas OST achieved only a 1.5 log 10 TCID 50 /ml reduction [6]. Previous reports have similarly demonstrated that baloxavir has a greater antiviral effect than OST: a network meta-analysis of past randomized controlled trial data showed that baloxavir-treatment was significantly more effective in reducing infectious viral tires at 24 hours after administration than OST, and other NAIs including zanamivir and peramivir [24].…”