PIN7 A NETWORK META-ANALYSIS OF THE EFFICACY AND SAFETY OF BALOXAVIR MARBOXIL VERSUS NEURAMINIDASE INHIBITORS IN THE TREATMENT OF INFLUENZA VIRUS INFECTION IN HIGH-RISK PATIENTS

Abstract

Baloxavir marboxil (BXM) is the first cap-dependent endonuclease inhibitor being studied for the treatment of influenza using a one-time oral dosing regimen. The relative efficacy and safety of BXM compared to other antiviral treatments for influenza in high-risk patients was evaluated with a network meta-analysis (NMA). A systematic literature review was performed in Medline, Embase, CENTRAL and ICHUSHI up to August 8th, 2018 to identify randomized controlled trials assessing antivirals in high-risk influenza. A Bayesian NMA was performed to compare BXM with antivirals (oseltamivir 75 mg BID for 5 days, zanamivir 10 mg BID for 5 days, laninamivir 40 mg single administration, peramivir 600 mg single or repeated administration) on efficacy (time to alleviation of all symptoms (TTAS), change in virus titer from baseline to 24h, rate of total complications) and drug-related adverse events (AEs). Ten trials were included in the NMA. The fixed effect model was selected based on the deviance information criterion for all outcomes. BXM was associated with a shorter TTAS compared with zanamivir, laninamivir, oseltamivir and peramivir; however the difference did not reach statistical significance. Mean decline in virus titer from baseline to 24h was significantly greater for BXM when compared with oseltamivir (difference in mean [95% credibility interval]: 1.60 [1.27; 1.93] log10TCID50/mL), and peramivir (1.46 [0.65; 2.26] log10TCID50/mL). The risk of total complications for BXM did not differ significantly from zanamivir, oseltamivir and laninamivir. The risk of drug-related AEs was comparable between BXM and zanamivir, peramivir, and laninamivir. BXM led to a significant decrease in virus titer at 24h versus oseltamivir and peramivir and non-significant decrease in TTAS versus all assessed antivirals. These findings are consistent with a previously conducted NMA on otherwise healthy patients. No significant differences were shown between BXM and other antivirals regarding the safety profile.