Oseltamivir does not prevent flu related hospitalizations: JAMA

Before the COVID-19 pandemic, influenza was one of the most clinically burdensome respiratory viruses. It is reported that COVID-19 temporarily reduced infections, but now influenza is expected to resurge. However, despite the substantial influenza threat, no evidence-based outpatient treatments are proven to prevent the progression to hospitalization.

Oseltamivir (Tamiflu) is an antiviral commonly prescribed to outpatients with influenza to fasten recovery and prevent complications. Despite its widespread use, summary evidence from prior meta-analyses has contradictory conclusions regarding whether oseltamivir reduces hospitalization risk when given to outpatients. Several large investigator-initiated randomized clinical trials have not yet been meta-analyzed.

Ryan Hanula, McGill University Health Centre, Montreal, Quebec, Canada, and the team therefore aimed to assess the safety and efficacy of oseltamivir in preventing hospitalization among influenza-infected adult and adolescent outpatients.

For this purpose, the researchers searched the online databases from inception to January 4, 2022. They included randomized clinical trials (RCTs) comparing oseltamivir versus placebo or nonactive controls in outpatients with confirmed influenza infection. Fifteen studies were included in the 2352 identified studies. The intention-to-treat infected (ITTi) population comprised 6295 individuals, and 54.7% were prescribed oseltamivir.

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) reporting guidelines were followed. Data were extracted and assessed by two independent reviewers. The quality of evidence was graded using the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) framework.

The study led to the following findings:

• Across study populations, 53.6% were female, and the mean age was 14.5 years.
• Oseltamivir was not associated with a reduced risk of hospitalization within the ITTi population (RR, 0.77; RD, −0.14%).
• Oseltamivir was also not associated with reduced hospitalization in older populations (mean age ≥65 years: RR, 0.99) or in patients considered at greater risk of hospitalization (RR, 0.90).
• Within the safety population, oseltamivir was associated with increased nausea (RR, 1.43) and vomiting (RR, 1.83) but not severe adverse events (RR, 0.71).

"Based on the available data, we found a lack of convincing evidence that oseltamivir reduces severe complications in outpatients with influenza," the authors wrote. "However, its use is associated with increased nonsevere gastrointestinal adverse events." They noted that the meta-analysis provides

"Future studies should focus on the conduct of an adequately powered placebo-controlled trial in a suitably high-risk population," they concluded.

Reference:

Hanula R, Bortolussi-Courval É, Mendel A, Ward BJ, Lee TC, McDonald EG. Evaluation of Oseltamivir Used to Prevent Hospitalization in Outpatients With Influenza: A Systematic Review and Meta-analysis. JAMA Intern Med. Published online June 12, 2023. doi:10.1001/jamainternmed.2023.0699