Oseltamivir and baloxavir marboxil to treat or prevent influenza A and B

Background: In Switzerland, the antivirals oseltamivir (Tamiflu®) and baloxavir marboxil (baloxavir, Xofluza®) are approved for treatment and prevention of influenza A and B. Since the demand for antiviral drugs can quickly and massively increase during influenza pandemics, Switzerland established a stockpile of oseltamivir in 2012. It has been questioned whether oseltamivir should remain in the stockpile or whether it should be replaced or supplemented with baloxavir. To inform these strategic stockpiling decisions, a clinical evidence synthesis regarding the efficacy and safety of oseltamivir and baloxavir is of interest. Objective: This report presents the clinical evidence on the efficacy and safety of oseltamivir and baloxavir to treat or prevent influenza A and B. Research questions: 1) Are oseltamivir and baloxavir efficacious and safe compared to each other, placebo or any non-antiviral treatment in patients with influenza A or B? 2) Are oseltamivir and baloxavir efficacious and safe compared to each other, placebo or any non-antiviral treatment in persons receiving prophylactic treatment against influenza? Methods: A systematic literature search in Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Medline and Web of Science databases was conducted. Eligible studies were randomised controlled trials (RCTs) that compared oseltamivir and baloxavir to each other, placebo or any non-antiviral treatment and assessed relevant outcomes such as mortality, influenzaassociated symptoms or complications and first hospitalisation. In addition, RCTs registered with clinicaltrials.gov and the WHO International Clinical Trials Registry Platform were searched, and their completion status was checked. Where possible, meta-analyses were performed to estimate pooled effect estimates. Heterogeneity among pooled effect estimates was explored by subgroup and sensitivity analyses. Outcomes which could not be pooled with meta-analyses were summarised narratively by using the Synthesis Without Meta-analysis (SWiM) guideline. Results were analysed separately for “patients with influenza-like symptoms” and “patients with confirmed influenza”. The methodological quality of included RCTs were critically appraised according to the Cochrane Risk of Bias tool 2 for randomised trials (RoB 2). The certainty of evidence was assessed for selected outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for pairwise meta-analyses. Results: The results summarised here are based on meta-analyses; more results were retrieved, summarised narratively, and shown in the report.