PIN4 A NETWORK META-ANALYSIS OF THE EFFICACY AND SAFETY OF BALOXAVIR MARBOXIL VERSUS NEURAMINIDASE INHIBITORS IN THE TREATMENT OF INFLUENZA VIRUS INFECTION IN OTHERWISE HEALTHY AND HIGH-RISK ADULTS

Abstract

Baloxavir marboxil (BXM) is the first cap-dependent endonuclease inhibitor which was 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 adults with uncomplicated influenza were evaluated with a network meta-regression (NMR). A systematic literature review was performed in Medline, Embase, CENTRAL and ICHUSHI up to August 8th, 2018. A Bayesian NMR was performed to compare BXM with oseltamivir, zanamivir, laninamivir and peramivir on time to alleviation of symptoms (TTAS), change in virus titer from baseline to 24h and drug-related adverse events (DRAEs) adjusting for the proportion of high-risk patients in each trial. Thirty-two trials were included in the NMR. No interaction between the proportion of HR patients and treatments effects was observed. BXM was associated with a significantly shorter TTAS compared to zanamivir (difference in median [95% Crl]: 19.00 [5.72; 39.31] hours) and with a shorter TTAS compared with laninamivir, oseltamivir and peramivir; however the probability of negative difference did not reach 95%. Mean decline in virus titer from baseline to 24h was significantly greater for BXM when compared with oseltamivir (difference in mean [95% Crl]: 2.05 [1.43; 2.70] log10TCID50/mL), peramivir 300mg (2.08 [1.26; 2.94]), peramivir 600mg (1.94 [1.10; 2.81]) and zanamivir (2.27 [1.19; 3.34]). The risk of DRAEs was lower for BXM than for oseltamivir (OR [95%Crl]: 1.64 [1.20; 2.25]) and laninamivir (OR [95%Crl]: 1.79 [1.05; 3.09]), and comparable to peramivir and zanamivir. These results are consistent with previously conducted NMA in otherwise healthy and high-risk patients separately. BXM demonstrated superior or similar efficacy results compared to other antivirals with a comparable or better safety profile in otherwise healthy and high-risk patients. Specifically BXM led to a significant virus reduction in titer versus zanamivir, oseltamivir and peramivir.